3. Human developmentHuman development
How a human develops from a fertilized egg into an embryo,How a human develops from a fertilized egg into an embryo,
and then a fetusand then a fetus. .
Some basicsSome basics::
1-Fertilization1-Fertilization (A male sperm and female egg fuse(A male sperm and female egg fuse
to form a zygote) (fertilised egg)-------( 0-24 hours).to form a zygote) (fertilised egg)-------( 0-24 hours).
The zygote is totipotent: it can produce all the cell typesThe zygote is totipotent: it can produce all the cell types
needed to make a complete human.needed to make a complete human.
4. 2-Cleavage (The zygote divides into two
identical cells). These cells then cleave and the
process repeats to form a ball of around 100
cells( 1-4 days).
-This happens while the zygote passes down the
fallopian tube towards the uterus (womb).
5. .
3-Blastocyst formation (The ball of cells
begins to specialize forming an outer layer of cells
with a cluster of cells inside (inner cell mass) (5-14
days).
-Cells of the inner cell mass are pluripotent: they can form all cell
types of the human body except tissues which support the
embryo, such as the placenta.
-The inner cell mass is the source of one type of stem cell,
embryonic stem cells.
6. 4-Gastrulation (The cells in the inner cell
mass move to form three layers, each of
which will become different areas of the
embryo).(Week3)
-The 3 layers are the ectoderm, mesoderm and
endoderm.
-The first sign of the nervous system appearing (the
primitive streak) occurs at gastrulation
7. ..5-Organogenesis (The formation of body
organs). The embryo is called a fetus at 8 weeks
when the structures which will give rise to all
major organs are present.( Week 3-8)
- The ectoderm forms the skin, brain and nervous system; the
mesoderm forms muscle and the skeletal and circulatory systems
and the endoderm forms the gut lining and many of the
internal organs.
9. Definition of stem cell
An unspecialized cell that has the ability toAn unspecialized cell that has the ability to
continuously divide and differentiate intocontinuously divide and differentiate into
various kind(s) of cells/tissuesvarious kind(s) of cells/tissues. .
Stem cells have two important characteristicsStem cells have two important characteristics. .
11--They are unspecialized cells capable ofThey are unspecialized cells capable of
renewing themselves through cell division,renewing themselves through cell division,
sometimes after long periods of inactivitysometimes after long periods of inactivity. .
10. 22--Under certain physiologic or experimentalUnder certain physiologic or experimental
conditions, they can be induced to become tissue- orconditions, they can be induced to become tissue- or
organ-specific cells with special functionsorgan-specific cells with special functions
(differentiation(differentiation(. (.
--In some organs, such as the gut and bone marrow,In some organs, such as the gut and bone marrow,
stem cells regularly divide to repair and replace wornstem cells regularly divide to repair and replace worn
out or damaged tissuesout or damaged tissues. .
--In other organs such as the pancreas and the heart,In other organs such as the pancreas and the heart,
stem cells only divide under special conditionsstem cells only divide under special conditions. .
11. Why do scientists carry out research
on stem cells?
-In most cases our bodies use tissue stem cells to replace damaged or worn
cells. However, where the damage is extensive, this repair
mechanism can fail.
-Also, many tissues in our body, for example brain tissue,
cannot repair themselves efficiently.
-Also many degenerative diseases are not yet treatable by
modern medicine.
-Transplantation of organs such as the heart can be an option,
but it relies on a plentiful source of transplant organs, and
many are in short supply.
-So stem cell research has gained a lot of attention because it
has the potential to fill this gap in human medical therapies.
12. Possible uses of stem cells
1-To provide lab-grown human or animal tissue for identifying
new treatments for disease.
2-To produce new human tissue and organs to replace those
lost in injury or disease.
3-To repair tissue by stimulating stem cells already in the body.
4-To use stem cells from patients with inherited genetic
diseases to study how the disease develops.
5-To investigate human development to better understand
diseases like cancer.
13. Stem cells in toxicologyStem cells in toxicology
--They can provide sufficient quantities of tissue specificThey can provide sufficient quantities of tissue specific
human cells for screening or toxicity testing to thehuman cells for screening or toxicity testing to the
drugs and chemicals (models for cardiotoxicity,drugs and chemicals (models for cardiotoxicity,
hepatotoxicity, genotoxicityhepatotoxicity, genotoxicity(. (.
--They can provide human cell-based in vitro systems forThey can provide human cell-based in vitro systems for
safety evaluations to avoid failure in preclinicalsafety evaluations to avoid failure in preclinical
development of new therapeutic drugs, and to shift thedevelopment of new therapeutic drugs, and to shift the
focus of toxicology away from classical animalfocus of toxicology away from classical animal
experimentsexperiments. .
14. History of Human Stem CellsHistory of Human Stem Cells
--Stem cells have an interesting history that has beenStem cells have an interesting history that has been
somewhat tainted with debate and controversysomewhat tainted with debate and controversy..
--In the midIn the mid 1800,1800, it was discovered that cells wereit was discovered that cells were
basically the building blocks of life and that some cellsbasically the building blocks of life and that some cells
had the ability to produce other cellshad the ability to produce other cells..
--InIn 19681968,, the first bone marrow transplant was successfully usedthe first bone marrow transplant was successfully used
in treatment of severe combined immunodeficiencyin treatment of severe combined immunodeficiency..
--Since theSince the 19701970, bone marrow transplants have been used for, bone marrow transplants have been used for
treatment of immunodeficiencies and leukemiastreatment of immunodeficiencies and leukemias..
15. --InIn 19981998, James Thomson (University of, James Thomson (University of
Wisconsin-Madison) isolated cells from theWisconsin-Madison) isolated cells from the
inner cell mass of the early embryo, andinner cell mass of the early embryo, and
developed the first human embryonic stemdeveloped the first human embryonic stem
cell linescell lines..
--InIn 19981998, John Gearhart (Johns Hopkins, John Gearhart (Johns Hopkins
University) derived human embryonic germ cellsUniversity) derived human embryonic germ cells
from cells in fetal gonadal tissue (primordialfrom cells in fetal gonadal tissue (primordial
germ cellsgerm cells(.(.
16. .
--InIn 20062006,, researchers made another breakthroughresearchers made another breakthrough
by identifying conditions that would allow someby identifying conditions that would allow some
specialized adult cells to be "reprogrammed"specialized adult cells to be "reprogrammed"
genetically to assume a stem cell-like stategenetically to assume a stem cell-like state..
))Induced pluripotent stem cellsInduced pluripotent stem cells(.(.
--InIn OctoberOctober 20102010: Journal of Experimental Medicine: Journal of Experimental Medicine
that research showsthat research shows tissues made from a person'stissues made from a person's
stem cells could therefore be rejected, becausestem cells could therefore be rejected, because
mitochondrial genomes tend to accumulatemitochondrial genomes tend to accumulate
mutationsmutations..
17. --JanuaryJanuary 20122012: The human clinical trial of treating type: The human clinical trial of treating type
1 diabetes using cord blood-derived stem cells1 diabetes using cord blood-derived stem cells
achieved an improvement of C-peptide levels,achieved an improvement of C-peptide levels,
reduced the median glycated hemoglobin A1Creduced the median glycated hemoglobin A1C
(HbA1c) values, and decreased the median daily dose(HbA1c) values, and decreased the median daily dose
of insulin in both human patient groups with andof insulin in both human patient groups with and
without residual beta cell functionwithout residual beta cell function..
Therapy appears "so simple and so safeTherapy appears "so simple and so safe""
18. Classification of stem cellsClassification of stem cells
11--Stem cells can be classified based on their ability toStem cells can be classified based on their ability to
differentiate intodifferentiate into::
A-Totipotent stem cellsA-Totipotent stem cells
Each cell can form a complete organism (e.g., identical twinsEach cell can form a complete organism (e.g., identical twins(.(.
They exist only in early embryos(1-3)daysThey exist only in early embryos(1-3)days..
B- Pluripotent stem cellsB- Pluripotent stem cells
They can generate all of the different cell types found
in the body.
They exist in the undifferentiated inner cell mass of theThey exist in the undifferentiated inner cell mass of the
blastocyst(5-14)daysblastocyst(5-14)days..
C- Multipotent stem cellsC- Multipotent stem cells capable of producing many
cell types but not all cell types in the body.
They are derived from fetal tissue, cord blood and adult stemThey are derived from fetal tissue, cord blood and adult stem
cellscells..
19. .
2-Scientists classified stem cells based on its
source into three main types : (Embryonic
stem cells, tissue stem cells and induced
pluripotent stem cells(.
1-Embryonic stem cells (pluripotent(.
This type is obtained from early-stage embryos,
specifically from the inner cell mass of the blastocyst.
20. -Use of embryonic stem cells in research and therapy
development:
…Advantage
Have a strong ability to self-renew (Telomerase )
in the laboratory, resulting in a constant supply of
ES cells.
…Disadvantages
1-Genetically different to cells of potential
patients, so immune rejection could occur.
2-Ethical issues over embryo destruction.
21. 2-Tissue stem cells ( adult stem cells( :
-They are obtained
.Directly from the organ or tissue in which they
are found Such as bone marrow, blood, cornea, retina,
intestine, muscle, nervous system, brain, and skin.
-.Developing organs in the fetus, umbilical cord
and placenta.
-They are termed multipotent . For example, a brain
stem cell can become any cell type of the brain, but
not a muscle cell.
22. -Their role in the body is to replace cells which die
throughout life due to wear and tear or injury and
disease. (stem cells in bone marrow replace blood
cells(.
-They are ideal to use to investigate questions around
cell differentiation that are specific to a certain
tissue.
-Although tissue stem cell ability to differentiate isability to differentiate is
more limited than pluripotent stem cells, they alreadymore limited than pluripotent stem cells, they already
have a track record of success in cell-basedhave a track record of success in cell-based
therapiestherapies..
23. -Currently there are some effective treatments that use
tissue stem cells from donors but these treatments
carry a risk that donated cells will be rejected.
-Use of tissue stem cells in research and therapy
development:
…Advantages
1-If taken from the patient’s own body for use
in therapies, cells would be genetically identical to
that of the patient, avoiding the problem of
immune rejection.
2-There are less ethical considerations
compared with using embryonic stem cells.
24. …Disadvantages
1-They usually produce only a limited number of different
cell types.
2-Conditions supporting self-renewal in the laboratory
have only been identified for a few tissue stem cell types, for
instance skin and cornea.
3-Are found in very small numbers and are difficult to
isolate.
4-Their numbers decrease with age.
25. 33--Induced pluripotent stem cells (IPSInduced pluripotent stem cells (IPS.(.(
--Somatic cells can be reprogrammed geneticallySomatic cells can be reprogrammed genetically
to form pluripotent stem cellsto form pluripotent stem cells..
--These IPS cell lines will have DNA matching thatThese IPS cell lines will have DNA matching that
of the somatic cell donors and will be useful asof the somatic cell donors and will be useful as
disease models and potentially for allogenicdisease models and potentially for allogenic
transplantationtransplantation..
--This strategy will help researchers learn how toThis strategy will help researchers learn how to
reprogram cells to repair damaged tissues in thereprogram cells to repair damaged tissues in the
human bodyhuman body..
26. Current sources of stem cellsCurrent sources of stem cells
11--Early embryos created byEarly embryos created by in vitro fertilizationin vitro fertilization eithereither
.Those which are not needed for infertility.Those which are not needed for infertility
treatment (Spare embryostreatment (Spare embryos((
..Created specifically for researchCreated specifically for research from donated eggs
and sperm, using IVF methods or by activating donated
human eggs without the use of sperm
(parthenogenesis(..
22--Early embryos created by somatic (body) cell nuclearEarly embryos created by somatic (body) cell nuclear
transfer (transfer (SCNTSCNT), a procedure that bypasses the normal), a procedure that bypasses the normal
fertilization process by taking the genetic material fromfertilization process by taking the genetic material from
a cell in an adult’s body and fusing it with an empty egga cell in an adult’s body and fusing it with an empty egg
cellcell..
27. This is a form of therapeutic cloning, which would allow cellsThis is a form of therapeutic cloning, which would allow cells
to be customized for each individual and thereby minimizeto be customized for each individual and thereby minimize
the chances of tissue rejectionthe chances of tissue rejection..
33--Germ cells or organs of an aborted fetusGerm cells or organs of an aborted fetus..
44--Blood cells of the umbilical cord at the time of birthBlood cells of the umbilical cord at the time of birth..
55--Some adult tissues (such as bone marrowSome adult tissues (such as bone marrow(.(.
66--Mature adult tissue cells reprogrammed to behave like stemMature adult tissue cells reprogrammed to behave like stem
cellscells..
N.BN.B
In the UK, permission to create embryos for research
is granted only for very specific reasons, for instance in
cases where scientists are trying to use ES cells to study
a particular inherited disease.
29. How embryonic stem cells areHow embryonic stem cells are
grown in the laboratorygrown in the laboratory??
-The generation of human ES cells has been
controversial due to ethical issues concerning the
status of the embryo.
-Human embryonic stem cells are generated byHuman embryonic stem cells are generated by
transferring cells from a pre-implantation-stagetransferring cells from a pre-implantation-stage
embryo into a plastic laboratory culture dish thatembryo into a plastic laboratory culture dish that
contains a nutrient broth known as culture mediumcontains a nutrient broth known as culture medium..
--The cells divide and spread over the surface of the dishThe cells divide and spread over the surface of the dish..
30. --In the original protocol, the inner surface of theIn the original protocol, the inner surface of the
culture dish was coated with mouse embryonic skinculture dish was coated with mouse embryonic skin
cells specially treated so they will not dividecells specially treated so they will not divide..
--This coating layer (feeder layer) provide the cells aThis coating layer (feeder layer) provide the cells a
sticky surface to which they can attach and releasesticky surface to which they can attach and release
nutrients into the culture mediumnutrients into the culture medium..
-Researchers have now devised ways to growResearchers have now devised ways to grow
embryonic stem cells without mouse feeder cellsembryonic stem cells without mouse feeder cells..
31. This is a significant scientific advance because of the riskThis is a significant scientific advance because of the risk
that viruses or other macromolecules in the mousethat viruses or other macromolecules in the mouse
cells may be transmitted to the human cellscells may be transmitted to the human cells..
-If these cells keep self-renewing for many months when
grown in these conditions, and can still differentiate
when tested, they are called a stem cell line.
-Such cell lines can produce almost unlimited numbers
of pluripotent ES cells for research.
33. Stem Cell differentiationStem Cell differentiation
--Unspecialized stem cells give rise to specialized cellsUnspecialized stem cells give rise to specialized cells..
--There are two types of signals inside and outside cells thatThere are two types of signals inside and outside cells that
trigger each step of the differentiation processtrigger each step of the differentiation process..
11--The internal signalsThe internal signals are controlled by a cell's genes, which areare controlled by a cell's genes, which are
interspersed across long strands of DNA and carry codedinterspersed across long strands of DNA and carry coded
instructions for all cellular structures and functionsinstructions for all cellular structures and functions..
22--The external signalsThe external signals::
Chemicals secreted by other cells, physical contact withChemicals secreted by other cells, physical contact with
neighboring cells, and certain molecules in theneighboring cells, and certain molecules in the
microenvironmentmicroenvironment..
The interaction of signals during differentiation causes the cell'sThe interaction of signals during differentiation causes the cell's
DNA to acquire epigenetic marks that restrict DNADNA to acquire epigenetic marks that restrict DNA
expression in the cell and can be passed on through cellexpression in the cell and can be passed on through cell
divisiondivision..
34. How are embryonic stem cellsHow are embryonic stem cells
stimulated to differentiatestimulated to differentiate??
--As long as the embryonic stem cells in culture areAs long as the embryonic stem cells in culture are
grown under appropriate conditions, they cangrown under appropriate conditions, they can
remain undifferentiated (unspecializedremain undifferentiated (unspecialized(.(.
--But if cells are allowed to clump together to formBut if cells are allowed to clump together to form
embryoid bodies, they begin to differentiateembryoid bodies, they begin to differentiate
spontaneously. It is a good indication of healthyspontaneously. It is a good indication of healthy
culture but, it is not an efficient way to produceculture but, it is not an efficient way to produce
cultures of specific cell typescultures of specific cell types..
35. .. ---So, to generate cultures of specific types ofSo, to generate cultures of specific types of
differentiated cells scientists try to control thedifferentiated cells scientists try to control the
differentiation of embryonic stem cellsdifferentiation of embryonic stem cells..
-11--change the chemical composition of thechange the chemical composition of the
culture mediumculture medium..
-22--Alter the surface of the culture dishAlter the surface of the culture dish..
33--Modify the cells by inserting specific genesModify the cells by inserting specific genes..
36. --If scientists can reliably direct the differentiation ofIf scientists can reliably direct the differentiation of
embryonic stem cells ,they may be able to use theembryonic stem cells ,they may be able to use the
resulting differentiated cells to treat certain diseases inresulting differentiated cells to treat certain diseases in
the futurethe future..
--ResearchResearch is underway to develop various sources foris underway to develop various sources for
stem cells, and to apply stem cell treatments bystem cells, and to apply stem cell treatments by
transplanting cells generated from human embryonictransplanting cells generated from human embryonic
stem cells for many diseases and conditions such asstem cells for many diseases and conditions such as;;
38. How are adult stem cells beingHow are adult stem cells being
used todayused today??
Stem cell procedures currently provide life-savingStem cell procedures currently provide life-saving
treatments for patients with leukemia, lymphoma, othertreatments for patients with leukemia, lymphoma, other
blood disorders, and some solid tumorsblood disorders, and some solid tumors..
The three main technologies in use today areThe three main technologies in use today are::
11--Adult stem cell transplant: bone marrow stem cellsAdult stem cell transplant: bone marrow stem cells
--Stem cell technology has been used for more than 20Stem cell technology has been used for more than 20
years in bone marrow transplants, where the patient'syears in bone marrow transplants, where the patient's
bone marrow stem cells are replaced with those from abone marrow stem cells are replaced with those from a
healthy, matching donorhealthy, matching donor..
--If the transplant is successful, the stem cells will migrateIf the transplant is successful, the stem cells will migrate
into the patient's bone marrow and begin producinginto the patient's bone marrow and begin producing
new, healthy leukocytes to replace the abnormal cellsnew, healthy leukocytes to replace the abnormal cells..
39. --The methodThe method..
--When stem cells are needed from a bone marrowWhen stem cells are needed from a bone marrow
donor, the aspiration procedure uses a specialdonor, the aspiration procedure uses a special
needle inserted into the bone (typically theneedle inserted into the bone (typically the
femur or iliac crest) to collect the cellsfemur or iliac crest) to collect the cells..
--Although the procedure is uncomfortable it canAlthough the procedure is uncomfortable it can
be tolerated by both children and adultsbe tolerated by both children and adults..
--For stem cell transplants, aspiration will likely beFor stem cell transplants, aspiration will likely be
done in several locations to ensure plenty ofdone in several locations to ensure plenty of
stem cells are available for the transplantstem cells are available for the transplant..
40. 22--Adult stem cell transplant: peripheral blood stemAdult stem cell transplant: peripheral blood stem
cells (PBSCscells (PBSCs((
--Easier to collectEasier to collect..
--ObstaclesObstacles..
11--Most blood stem cells reside in the bone marrowMost blood stem cells reside in the bone marrow
,and a small number are present in the bloodstream,and a small number are present in the bloodstream..
22--PBSCs are sparse in the bloodstream, so collectingPBSCs are sparse in the bloodstream, so collecting
enough to perform a transplant can pose a challenge.enough to perform a transplant can pose a challenge.
3-Time consuming3-Time consuming
One aphaeresis donation may take up to eight hoursOne aphaeresis donation may take up to eight hours..
Sometimes two donations are done on separate days,Sometimes two donations are done on separate days,
with each collection taking four to six hourswith each collection taking four to six hours..
41. --So the donor receives the drug Filgrastim (neopogen)So the donor receives the drug Filgrastim (neopogen)
to move more stem cells from the bone marrowto move more stem cells from the bone marrow
into the bloodstreaminto the bloodstream..
--Filgrastim is administered daily by injection for fiveFilgrastim is administered daily by injection for five
days prior to collectiondays prior to collection..
--The methodThe method
Where the blood is drawn from the donor (similar toWhere the blood is drawn from the donor (similar to
a blood donation), and passed through a machinea blood donation), and passed through a machine
that extracts the stem cells and returns otherthat extracts the stem cells and returns other
portions of the blood to the donorportions of the blood to the donor..
42. 33--Umbilical cord blood stem cell transplantUmbilical cord blood stem cell transplant::
--Umbilical cords traditionally have been discarded asUmbilical cords traditionally have been discarded as
a by-product of the birth processa by-product of the birth process..
--In recent years, the stem-cell-rich blood found in theIn recent years, the stem-cell-rich blood found in the
umbilical cord has proven useful in treating theumbilical cord has proven useful in treating the
same types of health problems as those treatedsame types of health problems as those treated
using bone marrow stem cells and PBSCsusing bone marrow stem cells and PBSCs..
--Of all stem cell types, autologous harvesting involvesOf all stem cell types, autologous harvesting involves
the least riskthe least risk..
43. Disadvantages of Stem cell treatmentsDisadvantages of Stem cell treatments
11--May require immune-suppression because of aMay require immune-suppression because of a
requirement for radiation before the transplant torequirement for radiation before the transplant to
remove the patient's previous cells, or because theremove the patient's previous cells, or because the
patient's immune system may target the stem cellspatient's immune system may target the stem cells..
22--Pluripotency in the stem cells could also make itPluripotency in the stem cells could also make it
difficult to obtain a specific cell typedifficult to obtain a specific cell type..
--Undifferentiated cells can create tissues other thanUndifferentiated cells can create tissues other than
desired typesdesired types..
44. 33--Some stem cells form tumors after transplantation;Some stem cells form tumors after transplantation;
pluripotency is linked to tumor formation especiallypluripotency is linked to tumor formation especially
in embryonic stem cells, fetal proper stem cells,in embryonic stem cells, fetal proper stem cells,
induced pluripotent stem cellsinduced pluripotent stem cells..
44--Unexpected behavior of the cells.Unexpected behavior of the cells.
5- unknown long-term health effects5- unknown long-term health effects..
The inner cell mass (the part that would form the fetus) of the embryo is isolated and disrupted to form embryonic cell lines. This process destroys the embryo. Under special culture conditions, the cells of the embryonic lines can be coaxed to form certain kinds of differentiated cell types. In theory, these differentiated cells could be used to repair or replace defective cells or tissues.