regeneration pattern

MR. JOHN DAVE B. ORPILLA, LPT
Isabela State University – Cabagan Campus
1

Developmental Biology and Regeneration
are intricately connected fields of study
Shared Biological Processes: Both fields explore fundamental processes such as cellular
differentiation, morphogenesis, and gene regulation. Understanding these processes in
developmental biology provides insights into how organisms grow, while in regeneration,
similar processes are reactivated for tissue repair and regrowth. (Biological Development | Definition, Stages, Examples, Theory, & Facts, 1998)
Stem Cell Research: Both developmental biology and regeneration heavily involve the
study of stem cells. Developmental biology focuses on their roles in embryonic
development, while regeneration harnesses their potential to replace damaged or lost
tissues in adults. (Developmental and Regenerative Biology, n.d.)
Tissue Repair and Growth: Developmental biology studies natural tissue development,
providing a basis for understanding tissue repair mechanisms. Regeneration utilizes this
knowledge to stimulate tissue repair and regeneration in damaged or diseased organisms.
(Liu et al., 2021)
2

Regeneration
Regeneration is the biological process by which organisms can
repair, replace, or grow new cells, tissues, or organs to replace
damaged or lost structures, often involving the activation and
differentiation of specialized cells like stem cells. This remarkable
ability to restore function and form is found in various organisms and
plays a crucial role in tissue repair, wound healing, and, in some cases,
the complete restoration of lost body parts. (Lakna, 2019)
4

Regeneration
Vs. Repair
The main difference
between repair and
regeneration is that repair is
the restoration of tissue
architecture and function
after an injury whereas
regeneration is a type of
healing in which new growth
completely restores portions
of damaged tissue to their
normal state. (Lakna, 2019)
5

Types of
Regeneration
Regeneration is the ability of the fully developed
organism to replace tissues, organs, and
appendages. ‘Regeneration’ distinguishes
between two types of regeneration:
Epimorphosis where regeneration involves
growth of a new, correctly patterned structure as
a limb, and
Morphallaxis, where there is little new cell
division and growth, and regeneration of
structure occurs mainly by the repatterning of
existing tissue.
(Wolpert, 2011) 7

Cell proliferation and division are fundamental processes
in biology that allow living organisms to grow, develop, and
repair damaged tissues. (Lakna, 2019a)
While cell proliferation is a result of cell growth and cell
division, cell differentiation is a result of the regulation of
gene expression. (Lakna, 2019a)

Cell proliferation is the process responsible
for the increase of cell number. The two
stages of cell proliferation are cell growth and
cell division. During the growth, cells
synthesize new DNA and proteins required by
cell division where the parent cells divide to
produce daughter cells. The newly produced
cells can either replenish a particular cell
group or replace dead or damaged cells in
tissues. Moreover, cell proliferation is
balanced by apoptotic cell death and cell
differentiation. (Lakna, 2019a)
Most of the adult cells in animals enter the
cell cycle in order to get proliferated. Some of
these cells include smooth muscle cells,
fibroblasts, epithelial cells of internal organs,
and endothelial cells. The main purpose of
this proliferation is to replace the dead or
damaged cells. On the other hand, adult stem
cells are undifferentiated cells whose cell
proliferation allows them to replenish the
stem cell population and to replace dead and
damaged cells. (Lakna, 2019a) 10

Cell differentiation and fate
determination are fundamental
processes in developmental biology
that govern how cells become
specialized and acquire specific
functions in multicellular organisms.
These processes are crucial for the
formation of tissues and organs
during embryonic development, as
well as for the maintenance and
repair of tissues in adult organisms.
11

Cell Differentiation
Cell differentiation is the specialization of
cells as a result of differential gene expression.
And, the expression of a pre-determined set
of genes of the genome results in the
expression of only a selected set of proteins in
the cell. Thus, this causes the production of
different phenotypes in different cells.
Therefore, different cells produce different
morphological features. Also, they undergo
unique metabolic reactions inside the cell. As
a result, different cells become specialized to
perform different functions in the body of a
multicellular organism. (Lakna, 2018)
The cells with similar functions occur
in groups called tissues. Therefore, a particular
tissue contains morphologically similar cells
with the same function. Therefore, in order to
perform each function of the body, there is a
specialized type of tissue. (Lakna, 2018)
12

Cell Determination
Cell determination is the determination of the set
of genes that are to be expressed in a particular
group of cells. It occurs through the asymmetric
segregation of cytoplasmic determinants. These
cytoplasmic determinants can be either proteins or
mRNAs. Due to their asymmetric localization, one
daughter cell receives the majority of the
cytoplasmic determinants during cell division while
the other daughter cell receives a fewer number of
determinants. Thus, this makes the daughter cells of
the same cell division different. Therefore, these two
daughter cells have different cell fates. Lakna, 2018)
The main role of cytoplasmic determinants is to
select a set of genes that should be expressed in the
daughter cell. As a result, a part of the genome will
be expressed while the rest will remain unexpressed.
The majority of this determinants are the mRNAs
that encode transcription factors. Also, transcription
factors can serve as cytoplasmic determinants by
themselves. Thus, their asymmetric distribution can
alter the gene expression. Lakna, 2018) 13

Conclusion
Cell determination is a result of the
asymmetric segregation of cytoplasmic
determinants, which leads to the
selection of the genes to be expressed.
It determines the fate of the cells. On
the other hand, cell differentiation is
responsible for the functional
specialization of the cells. It occurs due
to the differential expression of genes.
Therefore, the main difference between
cell determination and cell
differentiation is the process and the
role in the cell specialization.
14

Apoptosis and
its Role In
Regeneration
Apoptosis is a programmed
cell death process that occurs
naturally in multicellular
organisms. It plays a crucial role
in various biological processes,
including development, tissue
homeostasis, and immune
response. In the context of
regeneration, apoptosis has
both positive and negative
impacts, depending on the
specific tissue or organism
involved.
15

Positive Role in Regeneration:
1.Tissue Remodeling: During regeneration, apoptosis helps in the removal
of damaged or dead cells, allowing for the remodeling of tissues and
organs. This process is vital for the formation of new, healthy tissue.
2.Regulatory Role: Apoptosis acts as a regulatory mechanism to control
cell populations. In regeneration, this control is essential to prevent
excessive cell growth, ensuring that the new tissue forms correctly without
abnormalities.
3.Stem Cell Activation: Apoptosis in surrounding tissues can signal nearby
stem cells to proliferate and differentiate. Stem cells are crucial in
regeneration because they can develop into various specialized cell types
needed to rebuild the damaged tissue.
4.Elimination of Abnormal Cells: Apoptosis helps in the elimination of cells
with genetic mutations or abnormalities. In the context of regeneration, this
ensures that the newly formed tissue is healthy and functional.
16

Negative Role in Regeneration:
1.Excessive Apoptosis: Too much apoptosis can lead to
excessive tissue loss, making it challenging for the tissue to
regenerate fully. This imbalance can result in impaired organ
function or even organ failure.
2.Inhibition of Regeneration: In some cases, apoptosis might
inhibit regeneration by preventing the growth and differentiation
of necessary cells. This is particularly relevant in organs with
limited regenerative capacity, such as the heart and nervous
system.
17

Examples of Regeneration and
Apoptosis:
1.Limb Regeneration in Salamanders: Studies on salamanders
have shown that apoptosis is essential in the early stages of limb
regeneration. The removal of damaged tissue through apoptosis
creates a regeneration-permissive environment, allowing the
formation of new limbs.
2.Liver Regeneration: After liver injury, apoptotic cells release signals
that promote the regeneration of hepatocytes (liver cells). This
controlled apoptosis ensures the restoration of liver function without
excessive scar tissue formation.
In summary, apoptosis plays a critical role in regeneration by
facilitating tissue remodeling, regulating cell populations, activating
stem cells, and eliminating abnormal cells. However, the balance of
apoptosis is crucial; too much or too little can have negative
consequences on the regeneration process.
18

Stem cells are the only cells in your body that make
different cell types, like blood, bone and muscle cells.
They also repair damaged tissue. Now, stem cells are
essential blood cancer and blood disorder treatments.
Medical researchers believe stem cells also have the
potential to treat many other diseases.
Stem cells do two things that no other cells can do:
1. They continuously renew and divide to make exact
replicas of themselves. Typical or normal cells multiply
and divide, but they have limited lifespans.
2. They’re the only cells that make specialized
(differentiated) cells to replenish or repair specific cell
types. Hematopoietic stem cells support blood and
immune cells. Basal stem cells support skin cells.
Mesenchymal stem cells support bone, cartilage,
muscle and fat.
19
(Professional, n.d.)

Stem cells are important for the work they do to build and maintain your
body. More than that, they’re essential to medical research. Researchers
study stem cells to:
Understand how diseases happen. Researchers cultivate (grow) stem cells
in various tissues and organs. Watching how stem cells change as they grow
may help researchers to understand how diseases develop.
Learn how stem cells could replace damaged or unhealthy cells.
Researchers are studying ways stem cells can become different kinds of cells
that can treat damage or disease in specific parts of your body. For example,
someday, researchers may make stem cells to treat severe burns by
replacing damaged skin.
Test new treatments and medications. Researchers use stem cells to
evaluate medications that may be more effective in treating specific diseases.
By using specially prepared stem cells, researchers can determine if a
treatment works and is safe before they give the drugs to people participating
in clinical trials. 20

Healthcare providers may classify stem cell types by the cells’ source or the cells’
function. Most people probably are more familiar with stem cell classification by
source:
Embryonic (pluripotent) stem cells.These cells have the power to become any cell
type. Medical researchers obtain embryonic stem cells from donated cord blood or
embryos developed during in vitro fertilization.
Tissue-specific (multipotent or unipotent) stem cells.These cells can make new stem
cells, but only for the tissue in which they live. For example, blood-forming stem cells
in your bone marrow can make new blood cells and platelets. But they can’t make
new lung or liver stem cells. Researchers obtain stem cells from donated tissue.
Induced pluripotent stem cells (iPSC). These are lab-made stem cells that resemble
and act like embryonic stem cells. Medical researchers use these cells to study how
tissues develop and how disease affects tissue, and to test new drugs and
treatments.
21

Topic:
Regeneration in
Simple and
Complex Organism
Hydrasimple - morphallaxis
22

Planariansimple - morphallaxis
23

Amphibianssalamnader - complex - morphallaxis
24

Organisms can Regenerate Includes the following
Arthropods – Many arthropods can regenerate their limbs and other appendages caused by injury.
Arachnids including scorpions can regenerate their venom.
The fruit fly Drosophila melanogaster can regenerate its gut and germline.
Annelids – They can regenerate their posterior and anterior body parts even after latitudinal bisection.
Echinoderms – Starfish, sea cucumber, sea urchins, and many more come under this category. They can
regenerate their damaged appendages, internal organs some parts of the central nervous system.
Planaria (Platyhelminthes) – It includes planarians that can regenerate their lost body parts.
Aves (Birds) – Some birds can regenerate their feathers.
Mammals –
Humans- can regenerate their lost tissues or organs. (Only specific tissue and organs)
Male deer- can regenerate their antlers annually.
Mice- can regenerate damaged tissues, hair follicles, fur, and skin.
Reptiles – Lizards, crocodiles, and many more come under this category. Lizard has the highest regenerative
capacity as compared to others.
Lizard-Tail regeneration
Crocodile-Maxillary bone regeneration.
Chondrichthyes – Leopard sharks, bamboo sharks, and many more sharks come under this category.
Leopard sharks- regenerate their teeth after every 9-12 days because their teeth developed within the bony cavity.
Bamboo sharks- regenerate two-thirds of their liver.
Other sharks can regenerate their scales and even damage their skin.
25
(GeeksforGeeks, 2022)

Topic: Environmental Influence on Regeneration
in Developmental Biology
Environmental factors play a significant role in influencing regeneration processes in various organisms
1. Temperature and Climate:
Cold-blooded vs. Warm-blooded Animals: Cold-blooded animals (ectotherms) often show higher
regenerative abilities in warmer environments. This is because their metabolic rate and regenerative
processes are influenced by temperature. Warm-blooded animals (endotherms) have more stable internal
environments, which might not favor extensive regeneration.
Seasonal Changes: Regeneration abilities can vary with seasons. Some organisms might regenerate more
efficiently during specific seasons due to favorable environmental conditions.
2. Availability of Resources:
Nutrient Availability: Regeneration requires a lot of energy and resources. Availability of nutrients in the
environment directly influences an organism's ability to regenerate. Limited nutrients might hinder the
regeneration process.
Water Supply: Adequate hydration is crucial for regeneration. Aquatic organisms often have higher
regenerative abilities due to their constant access to water, which is essential for cellular processes.
26

3. Presence of Predators and Competition:
Predation Pressure: High predation pressure can lead to
evolutionary selection for enhanced regenerative abilities. Organisms
that can regenerate lost body parts have a better chance of survival if
they are preyed upon.
Competition: In competitive environments, organisms that can
regenerate and recover from injuries quickly might have a better
chance of outcompeting others for resources and mates.
4. Pollution and Environmental Stressors:
Pollutants: Chemical pollutants in the environment can negatively
affect regeneration. Pollutants might interfere with cellular processes,
making regeneration less efficient or causing abnormalities in
regenerated tissues.
Physical Stressors: Factors like radiation, habitat destruction, or
other physical stressors can impede regeneration processes by
damaging cells or disrupting the regenerative environment.
27

5. Social and Behavioral Factors:
Social Structure: Social animals might have different regenerative
abilities based on their social structure. Dominant individuals might
experience less stress and have better access to resources,
potentially influencing their regeneration abilities.
Behavioral Responses: Organisms might alter their behavior in
response to environmental cues, affecting their likelihood of injury and
subsequent regeneration. For example, some animals might become
more cautious in dangerous environments, reducing the risk of
injuries.
6. Adaptations and Evolution:
Evolutionary History: The regenerative abilities of an organism are
often shaped by its evolutionary history and the environmental
challenges faced by its ancestors. Species that evolved in
environments with high predation pressure might have developed
superior regenerative capabilities over time. 28

Topic: Regeneration and
Developmental Timing
Regeneration and developmental
timing are intricate processes that
govern the growth, differentiation, and
repair of tissues and organs in living
organisms. While these processes are
distinct, they share underlying
biological mechanisms and are
influenced by genetic and
environmental factors.
29

Cellular Plasticity
Regeneration requires cellular plasticity, where cells can revert to a
less specialized state to proliferate and differentiate into different cell
types. Developmental timing influences the plasticity of cells; certain
cells might retain their ability to differentiate into various cell types
even after the typical developmental window has passed, enabling
regeneration in specific organisms. (Lumen Learning, n.d.)
There are two types of plasticity:
experience-expectant and experience-dependent
In experience-expectant plasticity, external inputs during critical
developmental windows guide normal development of the brain.
In contrast, experience-dependent plasticity occurs throughout life and is
shaped by individual experiences
31

Regulatory Pathways: Both regeneration and
developmental timing are controlled by common
signaling pathways and genetic networks. For
instance, pathways like Wnt, BMP, and Notch are
involved in both development and regeneration. The
regulation of these pathways during development
can influence an organism's regenerative abilities. (The
Notch Signaling Pathway in Embryogenesis | Embryo Project Encyclopedia, 2013)
Environmental Influences: Environmental factors,
such as injury or stress, can trigger regeneration by
disrupting normal developmental processes. In
some cases, these external cues can activate
dormant stem cells or modify developmental timing,
allowing regeneration to occur. 33

REFERENCES 13
• Wolpert, L. (2011). 10. Regeneration. In Oxford University Press eBooks (pp. 106–112).
https://doi.org/10.1093/actrade/9780199601196.003.0011
• Liu, Y., Lou, W. P., & Fei, J. (2021). The engine initiating tissue regeneration: does a common mechanism exist
during evolution? Cell Regeneration, 10(1).
https://doi.org/10.1186/s13619-020-00073-1
• S, V. S. (2021, May 7). TISSUE REPAIR: General concepts & Mechanism of Regeneration - Pathology Made
Simple. Pathology Made Simple.
https://ilovepathology.com/tissue-repair-general-concepts-mechanism-of-regeneration/
• Developmental and regenerative biology. (n.d.).
https://drb.hms.harvard.edu/
• Biological development | Definition, Stages, Examples, Theory, & Facts. (1998, September 8). Encyclopedia
Britannica.
https://www.britannica.com/science/biological-development/Morphogenesis
• Lakna. (2019, May 24). What is the Difference Between Repair and Regeneration. Pediaa.Com.
https://pediaa.com/what-is-the-difference-between-repair-and-
regeneration/#:~:text=The%20main%20difference%20between%20repair%20and%20regeneration%20is,portions%
20of%20damaged%20tissue%20to%20their%20normal%20state.
• Lakna. (2019a, January 3). What is the Difference Between Cell Proliferation and Cell Differentiation. Pediaa.Com.
https://pediaa.com/what-is-the-difference-between-cell-proliferation-and-cell-
differentiation/#:~:text=Cell%20proliferation%20refers%20to%20the%20process%20which%20results,specialized
%20cell%20becomes%20a%20more%20specialized%20cell%20type.
34

• Lakna. (2018, December 3). What is the Difference Between Cell Determination and Cell Differentiation.
Pediaa.Com.
https://pediaa.com/what-is-the-difference-between-cell-determination-and-cell-
differentiation/#Cell%20Determination
• Professional, C. C. M. (n.d.). Stem cells. Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24892-stem-cells
• GeeksforGeeks. (2022, October 14). Regeneration.
https://www.geeksforgeeks.org/regeneration/
• Lumen Learning. (n.d.). The Lifespan Perspective | Lifespan Development.
https://courses.lumenlearning.com/wm-lifespandevelopment/chapter/the-lifespan-perspective/
• Embree, M. C., Lee, C., Dong, Z., Chen, M., Kong, K., Nie, H., Mendelson, A., Shah, B., Cho, S., Suzuki, T.,
Yang, R., Jiang, N., Mao, J. J., & Peter, X. (2015). Endogenous stem/progenitor cell recruitment for tissue
regeneration. In Cambridge University Press eBooks (pp. 405–418).
https://doi.org/10.1017/cbo9780511997839.027
• The Notch Signaling Pathway in Embryogenesis | Embryo Project Encyclopedia. (2013, March 6).
https://embryo.asu.edu/pages/notch-signaling-pathway-
embryogenesis#:~:text=The%20Notch%20signaling%20pathway%20is%20a%20mechanism%20in,the%20fo
rmation%2C%20growth%2C%20and%20development%20of%20embryos%20%28embryogenesis%29.
35

MR. JOHN DAVE B. ORPILLA
36

INTRODUCTION:
The regeneration pattern in embryonic development refers to the process
by which organisms repair, replace, or restore lost or damaged tissues and organs
during the early stages of their development. In this context, regeneration pattern
specifically refers to the series of biological events and mechanisms that enable
embryos to rebuild or recreate specific tissues and structures that have been injured
or lost.
During embryonic development, cells possess a high degree of plasticity,
meaning they can differentiate into various cell types. This plasticity allows them to
replace damaged or lost cells and contribute to the formation of tissues and organs.
Regeneration patterns involve processes such as cell proliferation, differentiation,
migration, and tissue morphogenesis, all of which are tightly regulated by complex
molecular and cellular mechanisms. These mechanisms ensure that the developing
organism can recover from injuries and continue its normal growth and
development. The ability to understand and manipulate these regeneration patterns
holds significant potential for regenerative medicine, tissue engineering, and
developmental biology research. 37

Topics:
•Embryonic Stem Cell
•Cellular Reprogramming
•Wound Healing and
Dedifferentiation
•Cell Proliferation
•Redifferentiation
•Regeneration Factors and
Signaling Pathway
•Environmental Influence
•Challenges and Applications
38

There are
three
types of
stem
cells:
40
Embryonic stem cells
Adult stem cells
Induced Pluripotent
Stem Cells (iPSC)

41
(Sudulaguntla et al., 2016)

Embryonic stem cells (ES cells) are pluripotent cells
derived from the inner cell mass of a blastocyst, which is a very
early stage embryo, usually around 5 to 7 days old. These cells
are called pluripotent because they have the remarkable
potential to differentiate into any cell type in the human body.
In other words, they can develop into cells of various tissues
and organs, such as neurons, muscle cells, blood cells, and
more(Lo & Parham, 2009).
Embryonic stem cells are unique in their ability to
divide and replicate indefinitely in culture while maintaining
their pluripotent state. This property makes them invaluable for
scientific research and potential medical applications. Scientists
study embryonic stem cells to better understand human
development, diseases, and to develop new therapies for various
medical conditions (Lo & Parham, 2009).
However, the use of embryonic stem cells is a topic of
ethical debate, as their derivation involves the destruction of
human embryos. This has led to the exploration of alternative
methods, such as induced pluripotent stem cells (iPSCs), which
are created by reprogramming adult cells to a pluripotent state,
eliminating the need for embryos in stem cell research and
therapy development(Lo & Parham, 2009).
42
(Print, 2017)

Topic:
Cellular
reprogramming in
embryonic development is
a fundamental process that
plays a crucial role in the
formation and
differentiation of various
cell types. It involves the
ability of cells to change
their fate or identity by
altering their gene
expression patterns. 44

Cellular reprogramming refers to the
process of converting a specialized cell, such
as a skin cell or a blood cell, back into an
unspecialized, pluripotent state. Pluripotent
cells are cells that have the potential to
develop into any cell type in the human body.
This reprogramming process erases the cell's
specialized characteristics and allows it to
regain the ability to differentiate into various
cell types.
45

The most well-known method of cellular reprogramming is induced
pluripotent stem cell (iPSC) technology, which was developed in 2006 by
Shinya Yamanaka and his colleagues. iPSCs are generated by introducing
specific transcription factors into adult, differentiated cells, which reprogram
the cells and turn back their developmental clock, making them pluripotent
again. These iPSCs can then be coaxed into differentiating into various cell
types, providing a potentially unlimited source of cells for regenerative
medicine, disease modeling, and drug testing.
Cellular reprogramming has significant implications in the fields of
regenerative medicine and biomedical research. By understanding the
mechanisms behind reprogramming, scientists hope to develop new
therapies for various diseases and conditions, as well as gain insights into the
fundamental processes of cell development and differentiation.
46

There are different types of cellular reprogramming, including
direct reprogramming (also known as transdifferentiation), which refers to
cell fate conversion without transitioning through an intermediary
pluripotent state. Direct reprogramming has become a promising strategy
to produce functional cells for therapeutic purposes, as it allows the
production of stem cells for biomedical research without the use of
embryos. (Wang et al., 2021)
Reprogramming is defined into three phases: initiation, maturation,
and stabilization. The properties of cells obtained after reprogramming
can vary significantly, in particular among iPSCs, and factors leading to
variation in the performance of reprogramming and functional features of
end products include genetic background, tissue source, reprogramming
factor stoichiometry, and stressors related to cell culture. (How Scientists
Reprogram Cells to Research Diseases | ISCRM, 2021)
47

Principles of indirect and direct
reprogramming. 48
(Wang et al., 2021) PUBMED NCBI

Topic:
In embryonic development, wound healing and dedifferentiation play critical
roles in shaping the developing organism, ensuring proper tissue formation, and
repairing any damage that might occur during development.
Both wound healing and dedifferentiation are intricately involved in embryonic
development. Wound healing ensures that any damage or disruptions in tissue integrity
are repaired, allowing the embryo to continue its development successfully.
Dedifferentiation, on the other hand, contributes to the plasticity of cells, enabling them
to change their fate and participate in various developmental processes, including
tissue remodeling and regeneration. These processes are tightly regulated and
coordinated to ensure the proper formation of tissues and organs in the developing
embryo. 49

Embryonic Wound Healing
Embryonic wound healing refers to the process of tissue repair and
regeneration that occurs in the early stages of development, specifically during
the embryonic and fetal periods. This type of wound healing is distinct from
the wound healing process that occurs in adults and has fascinated researchers
due to its remarkable ability to regenerate tissues without scarring. (Degen &
Gourdie, 2012)
During embryonic wound healing, the developing organism has the
ability to repair damaged tissues completely, often restoring normal structure
and function without leaving a scar. This is in contrast to adult wound healing,
where the repair process typically involves the formation of scar tissue(Abaffy
et al., 2019). 50

Several key differences exist between embryonic
wound healing and wound healing in adults:
Regeneration vs. Repair: In embryonic wound healing,
damaged tissues often undergo regeneration, wherein the
lost or damaged cells are replaced with new, healthy cells.
This regenerative process leads to the restoration of normal
tissue structure and function. In contrast, adult wound
healing typically involves repair processes, where the
damaged tissue is replaced by scar tissue, which lacks the
original tissue's functionality.
Inflammatory Response: The inflammatory response in
embryonic wound healing is tightly regulated and balanced,
preventing excessive inflammation that can lead to scar
formation. In adult wound healing, the inflammatory
response can be prolonged or dysregulated, contributing to
the formation of scars. 51

Several key differences exist between embryonic
wound healing and wound healing in adults:
Cellular Plasticity: During embryonic development, cells have higher
plasticity, meaning they can differentiate into various cell types needed
for tissue regeneration. This plasticity allows for the replacement of
damaged cells with specialized cells, promoting tissue regeneration
without scarring. In adults, most cells have limited plasticity, which
hampers the regeneration process.
Researchers study embryonic wound healing to understand the underlying
mechanisms that enable tissue regeneration without scarring. By deciphering these
processes, scientists hope to apply this knowledge to develop therapeutic approaches
for promoting tissue regeneration and reducing scarring in adult wound healing and
regenerative medicine applications. 52

Dedifferentiation in Embryonic Development
Dedifferentiation in embryonic development refers to the process by
which specialized cells lose their specific characteristics and revert to a more
primitive, undifferentiated state. In simpler terms, dedifferentiation is the
reverse of differentiation, where cells become less specialized and return to a
more embryonic or stem cell-like state. This process is essential during early
embryonic development when cells need to maintain their pluripotency,
meaning they have the potential to differentiate into various cell types.
During embryonic development, cells undergo a series of differentiation
steps to give rise to the various cell types and tissues in the body. However, in
certain situations, cells might need to dedifferentiate to repair damaged tissues
or regenerate lost cells. Dedifferentiation is a complex process regulated by
various signaling pathways and transcription factors.
54

During early embryonic development,
after fertilization of the egg by sperm, the zygote
undergoes a series of cell divisions through a
process called cleavage. These initial divisions
result in the formation of a blastocyst, a hollow ball
of cells. The cells within the blastocyst continue to
divide and differentiate, leading to the formation of
the three germ layers: ectoderm, mesoderm, and
endoderm. Each germ layer gives rise to specific
tissues and organs in the body (Lumen Learning &
OpenStax, n.d.).
Cell proliferation is tightly controlled by
various molecular signals, including growth
factors, signaling pathways, and cell cycle
regulators. The cell cycle consists of distinct
phases, including interphase (G1, S, and G2
phases) and mitosis (M phase). During the S phase
of interphase, DNA replication occurs, ensuring
that each daughter cell receives a complete set of
genetic information. Mitosis is the process of cell
division where a single cell divides into two
genetically identical daughter cells. Proper
regulation of the cell cycle is essential to prevent
abnormalities and ensure normal development
(Bouldin & Kimelman, 2014).
57

Cell proliferation, the process by which cells increase in number through division,
plays a central role in embryonic development. It is a fundamental mechanism that
drives the formation and growth of tissues and organs in a developing organism.
Here are some key roles of cell proliferation in embryonic development:
Formation of the Blastocyst: After fertilization, the zygote undergoes several rounds of cell division, forming a
blastocyst—a hollow ball of cells. Cell proliferation is essential during this stage to increase the number of
cells, allowing the blastocyst to develop and differentiate into the embryonic and extraembryonic tissues
(Cooper, 2000) .
Gastrulation and Germ Layer Formation: During gastrulation, a process where cells move and reorganize, cell
proliferation helps form the three primary germ layers: ectoderm, mesoderm, and endoderm. These layers give
rise to various tissues and organs in the body. Cell proliferation ensures there are enough cells to form these
layers and, later, to differentiate into specific cell types within each layer.(Cooper, 2000) .
Organogenesis: Cell proliferation continues during organogenesis, the process of organ formation.
Proliferating cells differentiate into specialized cell types, organizing into specific structures and tissues. Proper
cell proliferation ensures that organs reach the appropriate size and shape. For example, in the developing
brain, neural stem cells proliferate and differentiate into neurons and glial cells, forming the intricate neural
networks (Homem et al., 2015).
58

Tissue Growth and Remodeling: Cell proliferation contributes to the overall growth of tissues and organs. As
the embryo develops, cells continue to divide, allowing tissues to expand and take on their final forms.
Additionally, cell proliferation is involved in tissue remodeling, enabling the reshaping and restructuring of
organs as the embryo matures (Cislo et al., 2023).
Wound Healing and Regeneration: In some organisms, the ability to proliferate cells persists into adulthood
and is crucial for tissue repair and regeneration. While this is not specific to embryonic development, the
mechanisms of cell proliferation involved in wound healing and regeneration share similarities with those in
embryonic development (Cooper, 2000).
Maintenance of Stem Cell Populations: Throughout development, certain cells, such as stem cells, retain the
ability to proliferate and differentiate into various cell types. These stem cells are essential for tissue
maintenance, repair, and regeneration in both embryonic and adult organisms (Cancer Research UK, 2023).
59

Topic: REDIFFERENTIATION
Redifferentiation in embryonic development refers to the process by which
cells, tissues, or organs that have undergone dedifferentiation or lost their
specialized functions regain their specific characteristics and functions.
Dedifferentiation occurs when specialized cells revert to a less specialized or more
primitive state. This process is often associated with tissue regeneration, wound
healing, and embryonic development (Fehér, 2019).
During embryonic development, cells undergo a series of differentiation
events to give rise to various specialized cell types and tissues in the developing
organism. However, in certain situations, cells may need to redifferentiate to repair
damaged tissues or replace lost cells. Redifferentiation can occur through several
mechanisms, including:
61

Stem Cell Differentiation: Stem cells are undifferentiated cells that have the
potential to differentiate into various cell types. In embryonic development, stem
cells differentiate into specific cell lineages, and they can also be utilized for
tissue repair and regeneration in adult organisms(Liu et al., 2023) .
Transdifferentiation: Transdifferentiation is the process by which one
differentiated cell type transforms into another differentiated cell type without
first reverting to a stem cell-like state. This phenomenon has been observed in
various organisms and tissues during regeneration and repair processes
(Fehér, 2019).
Cell Fate Reprogramming: In some cases, mature, differentiated cells can be
reprogrammed to become pluripotent stem cells or induced pluripotent stem
cells (iPSCs). These cells can then be redifferentiated into different cell types.
This reprogramming can be achieved through genetic manipulation or by
introducing specific factors into the cells (Ramesh et al., 2009).
62

Tissue-specific Progenitor Cells: Some tissues in the body harbor specific
progenitor cells that are poised to differentiate into specialized cell types associated
with that tissue. These progenitor cells can divide and differentiate into mature cell
types during tissue repair and regeneration processes(Fehér, 2019) .
The ability of cells to redifferentiate is crucial for tissue repair, regeneration,
and embryonic development. Understanding the molecular mechanisms that
govern redifferentiation processes is a topic of active research in developmental
biology and regenerative medicine, as it holds the potential for applications in
tissue engineering, regenerative therapies, and disease treatment (Ji et al., 2023).
63

Dedifferentiation Redifferentiation
A cell can restore its ability to
process called dedifferentiation,
the function that was given to it
differentiation.
Redifferentiation is the process
dedifferentiated cell acquires a
loses its capacity to divide once
Cork cambium, wound meristem,
interfascicular vascular cambium
of dedifferentiated tissue that
meristematic tissue.
The tissue that has undergone
is the functionally specialized
Consequently, this is yet another
dedifferentiation and
The process of dedifferentiation
plant body to make new cells in a
region.
Redifferentiation is necessary to
task unique to a certain area of the
Dedifferentiation occurs when fully
parenchyma cells are used to create
interfascicular cambium and cork
One instance of redifferentiation is
specialization of the vascular
secondary xylem and phloem.
During development, cells undergo
substantial structural changes and
lignocellulosic secondary cell walls,
strong, elastic, and able to carry
distances.
Secondary xylem and secondary
are incapable of further cell
they have reached adulthood, they
range of functions, including
structural integrity of the plant.
Dedifferentiation Redifferentiation
1.The process by which a cell loses
its ability to divide and attains a
specific function is known as
differentiation.
1.The phenomenon by which cells
divide and produce cells that once
again lose their dividing capacity but
mature to perform specific
functions.
2. It is manifested by a gene
expression pattern, a change in the
shape, protein expression pattern,
and function.
2. It is both the process and the
result of developing additional new
characters.
3. Example: Interfascicular cambium
and meristems-cork cambium
formation from fully differentiated
parenchymal cells
3. Example: Formation of secondary
xylem and secondary phloem,
secondary cortex cork from the
interfascicular cambium, and cork
cambium.
Dedifferentiation vs. Redifferentiation
64
(Vedantu, n.d.) (Byju’s, 2022)

Topic:
Regeneration Factors
and Signaling Pathway
Regeneration in the context
of embryonic development
involves the ability of an organism
to replace or repair damaged or
lost tissues and structures. This
process is tightly regulated by a
combination of regeneration
factors and signaling pathways.
While the specific details can vary
among different organisms, here's
a general overview of regeneration
factors and signaling pathways
involved in embryonic
development and regeneration: 65

Regeneration
Factors
•Morphogens
•Extracellular Matrix (ECM)
Components
•Stem Cells
•Cytokines and Growth Factors
•Cell Adhesion Molecules
66

Morphogens as
Regeneration
Factor
Morphogens play a crucial role in
both embryonic development and tissue
regeneration by providing positional
information to cells, guiding their
differentiation and patterning. The
concept of morphogens was initially
introduced by Lewis Wolpert in the 1960s
as part of his positional information
theory (Kicheva & Briscoe, 2023).
Here's how morphogens
contribute to the regeneration pattern in
embryonic development:
67

Establishment of Tissue Patterns: Morphogens help establish spatial patterns of
different cell types within tissues and organs by forming concentration gradients
across developing tissues. Cells interpret these gradients to determine their
fate.
Cell Fate Determination: Morphogens act as signaling molecules that influence
cell fate decisions. Cells exposed to different concentrations of morphogens
may adopt distinct identities and follow specific developmental pathways
Gradient Sensing: Cells have the ability to sense and respond to the
concentration gradients of morphogens in their microenvironment. This
gradient sensing allows cells to "know" their position within a developing tissue
and make appropriate developmental decisions(Kicheva & Briscoe, 2023) .
68

Role in Regeneration: In the context of regeneration, morphogens continue
to play a vital role. When tissues are damaged or lost, the regeneration
process often involves the re-establishment of positional information to
guide the formation of new tissues.
Stimulation of Stem Cell Differentiation: Morphogens can influence the
differentiation of stem cells into specific cell types required for tissue repair.
Stem cells residing in or recruited to the damaged area respond to
morphogenic signals, leading to the generation of the necessary cell types
Tissue Patterning in Regeneration: Regeneration often involves the
reconstruction of complex tissue patterns. Morphogens contribute to this
process by providing the necessary cues for cells to organize themselves in a
specific spatial arrangement, ultimately recreating the functional
architecture of the damaged tissue
69

Extracellular Matrix (ECM)
Components as Regeneration Factor
The extracellular matrix (ECM) plays a
crucial role in the regeneration pattern of
embryonic development, providing structural and
biochemical support to surrounding cells. It is a
complex network of proteins and carbohydrates
that actively influences cell behavior, including
cell migration, proliferation, differentiation, and
tissue morphogenesis(Kusindarta &
Wihadmadyatami, 2018) .
During embryonic development,
regeneration relies heavily on the dynamic
interactions between cells and their surrounding
ECM. Several ECM components act as
regeneration factors, influencing the process in
various ways:
70

Collagens: Structural Support, providing tensile strength to tissues. During
regeneration, collagens create a scaffold that guides cell migration and
tissue organization (Assunção et al., 2020).
Fibronectin: Cell Adhesion, providing binding sites for cells through integrin
receptors, facilitating the movement of cells during regeneration(Hussey et
al., 2018) .
Laminins: Basal Lamina Formation, contributing to the formation of the
basal lamina, a specialized ECM layer. This structure serves as a platform
for cell attachment, differentiation, and tissue organization during
regeneration (Walma & Yamada, 2020).
Proteoglycans: Hydration and Compression Resistance, with their
glycosaminoglycan chains contributing to the hydrated gel-like nature of the
ECM. This property is essential for resisting compression forces and
maintaining tissue integrity during regeneration (Rozario & DeSimone,
2010).
71

Growth Factors and Cytokines: Signaling Molecules, sequestering and
releasing growth factors and cytokines to regulate cellular activities.
This includes processes like cell proliferation, differentiation, and
migration crucial for regeneration(Hussey et al., 2018).
Matrix Metalloproteinases (MMPs): Remodeling, playing a role in ECM
remodeling by breaking down and restructuring the ECM, allowing for
changes in tissue architecture during regeneration(Hussey et al., 2018).
Hyaluronic Acid: Tissue Hydration and Compression Resistance,
contributing to tissue hydration and providing resistance to
compression forces. It is involved in maintaining the structural integrity
of tissues during regeneration (Rozario & DeSimone, 2010).
72

Stem Cells as
Regeneration Factor
74
Stem cells play a crucial role in the regeneration pattern of embryonic development
due to their unique ability to differentiate into various cell types. During embryonic
development, stem cells contribute to the formation of tissues and organs through processes
such as cell proliferation, migration, and differentiation. There are two main types of stem
cells involved in embryonic development: embryonic stem cells (ESCs) and adult or somatic
stem cells (National Academies Press (US), 2002).
Embryonic Stem Cells (ESCs):
Pluripotency: ESCs are pluripotent, meaning they have the potential to differentiate into
any cell type in the body. During embryonic development, ESCs are responsible for the
formation of the three germ layers (endoderm, mesoderm, and ectoderm) and
subsequently give rise to all the different cell types in the body(National Academies Press
(US), 2002) .
Tissue and Organ Formation: ESCs contribute to the initial stages of tissue and organ
formation. They undergo differentiation into specific cell lineages that give rise to
structures such as the nervous system, cardiovascular system, and various organs
(National Academies Press (US), 2002).
Cell Replacement: ESCs are involved in the replacement of damaged or dying cells,
contributing to the overall growth and development of the embryo (National Academies
Press (US), 2002).

Cytokines and Growth Factors as
Regeneration Factor
The role of cytokines and growth factors as regeneration factors in
the pattern of embryonic development is a fascinating aspect of
developmental biology. These signaling molecules are critical for
orchestrating the complex processes involved in tissue regeneration during
embryogenesis. Here's a more focused discussion on how cytokines and
growth factors contribute to the regeneration pattern:
Cell Proliferation and Differentiation:
Cytokines and growth factors play a central role in promoting cell
proliferation and guiding the differentiation of stem cells into specific cell
lineages during embryonic development. For example, fibroblast growth
factors (FGFs) are involved in promoting cell division and differentiation
in various tissues.
Tissue Morphogenesis and Organogenesis:
The precise regulation of cytokines and growth factors is crucial for
tissue morphogenesis and organogenesis. Signaling molecules such as
bone morphogenetic proteins (BMPs) and Wnt proteins contribute to the
formation of distinct tissue structures and organ systems by guiding cell
differentiation and tissue patterning.
75

Cell Migration and Tissue Organization:
Chemotactic factors, including certain cytokines, guide cell migration to specific
locations, ensuring proper tissue organization. This is particularly important in the
formation of structures such as the neural tube, where cells need to migrate to
their designated positions for the development of the nervous system.
Angiogenesis:
Vascular endothelial growth factor (VEGF) is a key growth factor that promotes
angiogenesis, the formation of blood vessels. This process is crucial for establishing
a vascular network that provides nutrients and oxygen to developing tissues,
facilitating their growth and differentiation.
Regulation of Apoptosis:
Cytokines and growth factors also play a role in the regulation of apoptosis, or
programmed cell death. This is essential for sculpting tissues and organs by
eliminating excess or unnecessary cells, ensuring proper organ size and structure.
76

Stem Cell Maintenance and Self-Renewal:
Growth factors such as leukemia inhibitory factor (LIF) contribute to the maintenance
of pluripotent stem cells, ensuring their self-renewal capacity. This is vital for
sustaining a pool of undifferentiated cells that can contribute to tissue repair and
regeneration.
Environmental Sensing and Adaptation:
Cells in developing tissues respond to environmental cues provided by cytokines and
growth factors, adapting their behavior accordingly. This responsiveness allows for
dynamic adjustments in cell fate and function, contributing to the overall regeneration
pattern.
Regenerative Medicine Perspectives:
Understanding the roles of cytokines and growth factors in embryonic regeneration
provides valuable insights for regenerative medicine. Researchers aim to apply this
knowledge to stimulate tissue repair and regeneration in adults, potentially offering
therapeutic strategies for conditions where tissue damage or degeneration occurs. 77

Cell Adhesion Molecules as Regeneration
Factor
Cell adhesion molecules (CAMs) play crucial roles in
various biological processes, including embryonic
development and tissue regeneration. CAMs are proteins
located on the cell surface that mediate cell-cell and cell-
extracellular matrix interactions. They are involved in
processes such as cell migration, tissue organization, and
signal transduction, making them essential players in
embryonic development and regeneration.
In the context of embryonic development and tissue
regeneration, CAMs contribute to the establishment of tissue
architecture, cell differentiation, and the coordination of cellular
activities. Here are some ways in which CAMs function as
regeneration factors during embryonic development:
78

Cell Migration: During embryonic development, cells often need to
migrate to specific locations to form tissues and organs. CAMs aid in
this process by facilitating cell adhesion and migration. They provide a
substrate for cells to move along and interact with each other in a
coordinated manner .
Tissue Morphogenesis: CAMs contribute to the organization of cells
into specific structures and tissues. They help cells adhere to each
other and form stable connections, allowing the development of three-
dimensional tissue architectures. This is particularly important during
the early stages of embryonic development when organs and tissues
are being shaped (Shawky & Davidson, 2015).
Cell Differentiation: CAMs can influence cell fate and differentiation
by mediating cell-cell interactions. Cells receive signals through CAM-
mediated adhesion events that can lead to changes in gene
expression and cellular behavior, ultimately influencing the
differentiation of cells into specific cell types(Shawky & Davidson,
2015) .
79

Axon Guidance: In neural development, CAMs are critical for guiding axons
to their target destinations. Neuronal CAMs help establish connections
between neurons and their target cells, contributing to the formation of
neural circuits. This process is essential for proper nervous system
development and function.
Regulation of Signaling Pathways: CAMs can modulate intracellular signaling
pathways, influencing cell survival, proliferation, and differentiation. By
participating in signal transduction events, CAMs contribute to the regulation
of cellular activities crucial for both embryonic development and tissue
regeneration.
Wound Healing and Regeneration: In the context of tissue regeneration,
CAMs are involved in wound healing processes. They play roles in cell
migration to the injury site, the formation of provisional matrices, and the
coordination of tissue repair. CAMs contribute to the establishment of a
microenvironment conducive to regeneration.
80

Sub topic: Signaling Pathways Roles
in Regeneration Factor
• Wnt/β-Catenin Pathway
• Notch Signaling Pathway
• Fibroblast Growth Factor
(FGF) Pathway
• Transforming Growth Factor-
beta (TGF-β) Pathway
• Hedgehog Signaling Pathway
81

Wnt/β-Catenin Pathway:
Role in Regeneration: Wnt signaling is involved in various processes, including cell fate
determination and tissue regeneration. Activation of the Wnt/β-catenin pathway can stimulate cell
proliferation and tissue repair.
Notch Signaling Pathway:
Role in Regeneration: Notch signaling regulates cell fate decisions and is important for tissue
regeneration. It influences the differentiation of stem cells into specific cell types.
Fibroblast Growth Factor (FGF) Pathway:
Role in Regeneration: FGF signaling is critical for cell proliferation, migration, and differentiation
during embryonic development and regeneration. It is involved in the regeneration of various tissues.
Transforming Growth Factor-beta (TGF-β) Pathway:
Role in Regeneration: TGF-β signaling plays a dual role in regulating cell proliferation and
differentiation during embryonic development and regeneration. It can promote or inhibit regeneration
depending on context.
Hedgehog Signaling Pathway:
Role in Regeneration: Hedgehog signaling is involved in tissue patterning and regeneration. It
regulates cell differentiation and tissue repair in various developmental contexts.
82

Topic: Environmental Influence
The environmental influence on
the regeneration pattern of embryonic
development is a complex and
multifaceted process that can vary
across different species and contexts.
While genetics plays a fundamental
role in determining the basic blueprint
of an organism's development,
environmental factors can also
significantly impact the trajectory of
embryonic development and
regeneration.
83

84
• Temperature can affect the rate of embryonic development. In many species, the rate of
development increases with higher temperatures, and vice versa. Extreme temperatures
can also lead to abnormalities or developmental delays (Besenfelder et al., 2020).
Temperature:
• The availability of nutrients in the environment is crucial for the proper development of
embryos. Lack of essential nutrients or exposure to harmful substances can lead to
developmental abnormalities or hinder the regenerative capacity of tissues(Besenfelder
et al., 2020).
Nutrient Availability:
• Oxygen is essential for cellular respiration and energy production. Oxygen levels in the
environment can influence embryonic development. Hypoxia (low oxygen levels) or
hyperoxia (high oxygen levels) can have various effects on development, depending on
the organism(Besenfelder et al., 2020).
Oxygen Levels:

85
• Exposure to environmental pollutants, toxins, or certain chemicals can disrupt
normal embryonic development. This can lead to malformations, genetic
mutations, or other developmental abnormalities(Besenfelder et al., 2020).
Chemical Exposure:
• Mechanical forces, such as pressure or tension, can influence embryonic
development. For example, the mechanical properties of the surrounding tissue
can affect cell differentiation and tissue patterning(Besenfelder et al., 2020).
Mechanical Forces:
• In some species, social and behavioral factors can influence embryonic
development. For instance, the presence or absence of parental care may
impact the survival and development of offspring(Doi et al., 2022).
Social and Behavioral Factors:

86
• Photoperiod, or the duration of light and darkness in a day, can influence the timing
of developmental events in certain species. Light exposure may also affect
hormonal regulation, impacting embryonic development(Doi et al., 2022).
Photoperiod and Light:
• The microbiome, consisting of microorganisms living in and on the body, can
influence embryonic development. Microbial communities can affect immune
system development and overall health, impacting the organism's ability to
regenerate tissues(Doi et al., 2022).
Microbial Influence:
• Environmental stressors, such as changes in temperature, predation threats, or
habitat disruptions, can induce stress responses that influence embryonic
development. Stress hormones can affect gene expression and cellular
processes(Doi et al., 2022).
Stress:

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91

Modeling embryo
development using
stem cell technologies:
95

98
Fig. 1: Timeline of seminal events in the fields of
stem cell and developmental biology and in vivo
embryogenesis including in vitro counterparts.
Fig. 2: Schematic representation of the in
vivo embryo and corresponding in vitro
models of the pre- and peri-implantation
stages.

Challenges and Future
Prospects
99

100
Challenges and future directions in harnessing embryonic regenerative
processes for therapeutic purposes can be discussed based on the search
results. Some of the challenges and future directions include:
• Understanding developmental mechanisms: The successful outcome of
both development and regeneration is dependent on growth resulting from
cellular proliferation and on pattern formation. However, there is still a need
for further understanding of developmental mechanisms, especially in the
context of creating synthetic whole embryos.
• Improving tissue culture techniques: Researchers have made progress in
creating synthetic whole embryos, but there is still a need for further
understanding of developmental mechanisms to achieve the desired level of
complexity and morphological integrity

101
Advancing regenerative medicine: Stem cells and progenitor cells have the
potential to stimulate repair mechanisms and restore function in damaged
tissues. However, there are several issues that need to be addressed to
advance regenerative medicine as a field.
Comparing embryogenesis and regeneration: The relationship between
embryonic development and regeneration is not yet fully understood. Future
research should focus on identifying similarities and key differences between
these processes, as well as the factors that influence the competency and
extent of regenerative responses.
Exploring new therapeutic applications: Different approaches applied in
regenerative medicine have the potential to replace and overcome missing
organs or tissues. Future research should aim to develop new techniques and
tools for harnessing embryonic regenerative processes for therapeutic
purposes

To Conclude the Whole Discussion
Embryonic development is a highly orchestrated process involving cellular
differentiation, organogenesis, and morphogenetic movements. Signaling
pathways guide the precise differentiation of cells into specialized types,
contributing to the formation of distinct tissues and organs.
In conclusion, the exploration of the regeneration pattern in embryonic
development underscores the remarkable intricacies inherent in the formation
of tissues and organs. The orchestrated processes of cellular differentiation,
organogenesis, and morphogenetic movements reveal the sophisticated dance
of genetic and epigenetic regulation shaping the developing organism.
102

The distinctive regenerative potential exhibited by embryonic tissues, surpassing that
of their adult counterparts, holds significant promise for the field of regenerative medicine.
Insights garnered from embryonic development provide valuable guidance for strategies in
tissue engineering and therapeutic interventions. However, the translation of these insights
into clinical applications faces challenges that necessitate further investigation and
technological refinement.
The ongoing pursuit of understanding and harnessing embryonic regenerative
processes reflects a dynamic intersection of biology and medicine. Future directions in
research must address these challenges, emphasizing the need for innovative solutions to
fully leverage the potential of embryonic regeneration for practical medical advancements.
As we navigate these complexities, the study of embryonic development remains a beacon of
inspiration, offering a blueprint for regenerative strategies that could redefine the landscape
of healthcare and medical interventions in the years to come.
103

REFERENCES:
• Pedroza, M., Gassaloglu, S. I., Dias, N., Zhong, L., Hou, T., Kretzmer, H., Smith, Z. D., & Sözen, B. (2023).
Self-patterning of human stem cells into post-implantation lineages. Nature.
https://doi.org/10.1038/s41586-023-06354-4
• Kim, Y., Kim, I., & Shin, K. (2023). A new era of stem cell and developmental biology: from blastoids to
synthetic embryos and beyond. Experimental & Molecular Medicine, 55(10), 2127–2137.
https://doi.org/10.1038/s12276-023-01097-8
• Chen, K. Q., Anderson, A., Kawakami, H., Kim, J., Barrett, J., & Kawakami, Y. (2022). Normal embryonic
development and neonatal digit regeneration in mice overexpressing a stem cell factor, Sall4. PLOS ONE,
17(4), e0267273.
https://doi.org/10.1371/journal.pone.0267273
104

MR. JOHN DAVE B. ORPILLA, LPT
105

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