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STEM CELL
FOR
ARTIFICIAL ORGAN REGENERATION
INTRODUCTION
A stem cell is a cell with the unique ability to develop
into specialised cell types in the body.
There are three main types of stem cell:
• Embryonic stem cells
• Adult stem cells
• Induced pluripotent stem cells
Regeneration means the regrowth of a damaged or
missing organ part from the remaining tissue.
ORGANS THAT CAN BE REGENERATED USING STEM
CELL TECHNOLOGY
Heart
Liver
Brain
Bone
Esophagus
Kidney
Stomach
Lung
4
ECM
+
Stem cell
Assay
3
Lyophilization
2
Decellularization
1
PROCEDURE FOR PREPARING BIOINK FOR 3D BIO
PRINTING
This process is used to
isolate the
extracellular matrix
(ECM) of a tissue(SDS
& NaCl is been used
to remove the DNA
content)
It is basically a water
removal process
typically used to
preserve perishable
materials, to extend
shelf life
• DNA(< 2%)
• GAG
• Collagenase
Adding the
Stem Cell
along with
the ECM
DIGRAMETIC REPRESENTATION
Scaffolds are materials that have
been engineered to cause desirable
cellular interactions to contribute to the
formation of new functional tissues for
medical purposes.
1. Decellularized Tissue 2. Lyophilized Tissue 3. Assay 4. Organ Printing
MANUFACTURING PROCESSES OF
ARTIFICIAL ORGANS (BONES)
The various processes involved in the manufacturing of artificial organs involve the
following:
• Tissue Engineering: This is the use of a combination of cells, engineering and
materials methods, and suitable biochemical and physio-chemical factors to
improve or replace biological functions.
• Bio-printing or 3D printing of tissues: Bio-printing, where living cells are
precisely printed in a certain pattern, has great potential and promise for
fabricating engineered living organs.
• Industrially by using biomaterials which includes metals, ceramics, polymers and
composites.
• In the laboratory by using stem cells under Regenerative Medicine.
• GRAFT: A viable tissue that after removal
from a donor site is implanted with in a
recipient tissue is then restored, repaired and
regenerated.
• GRAFTING: It is a procedure used to
replace/restore missing bone or gum tissue.
• BONE GRAFTS: The materials used for the
replacement or augmentation of the bone.
OSTEOINDUCTION
Stimulation of
osteoprogenitor
cells
Osteoblasts
New Bone
Formation
BIOLOGICAL CONCEPTS IN BONE
GRAFTING
• Contains bone forming cells (osteogenesis)
• Serve as scaffold for bone formation
(osteoconduction)
• Matrix of bone grafting material contains bone
inductive substances (oteoinduction)
OSTEOGENESIS
Osteoblast
s in the
transplante
d bone
having
adequate
blood
supply and
cellular
viability
Forms
new
centre of
ossificati
on within
the graft
TYPES OF GRAFT TISSUE
AUTOGRAPHS
A tissue transferred from one position
to another within the same individual.
ALLOGRAPHS/HOMOGRAPHS
Obtained from genetically dissimilar
individual of same species.
XENOGRAPHS/HETEROGRAPHS
Tissue transferred from one species to
another species
ALLOPLASTS
A synthetic graft or inert foreign body
implanted into tissue.
BONE CELLS ARE
COMPOSED OF
Osteoblasts
Osteoclasts
Osteiods
Inorganic mineral sals
BONE
REGENERATION
Bone regeneration is process which response to any
injury like accidental fracture, development of
continuous remodelling of bone, disease condition
like osteoporosis and after surgery like arthoplasty,
etc. Bone regeneration process involves certain
processes like hematoma formation, callus
formation, callus ossification and bone remodelling
Need of Bone Regeneration
There are over 15 million fracture
cases globally and an estimated 2.2
million bone graft procedures are
performed annually to promote
fracture healing or to fill defects .
Sometimes the common solutions,
such as Autografts & Allografts are
not suitable due to the donor site
morbidity, disease transmissions,
and, for the implants case, failure
may occur after transplantation of
tissue.
Scaffolds
Polymeric
Natural
Bone
Morphogeni
c Proteins
Mesenc
hymal
cells and
Growth
Factors
APPROCHES TO BONE
REGENERATION
MESENCHYMAL STEM CELLS
Multipotent stromal cells that made up of different cell like: osteoblasts (bone cells),
chondrocytes (cartilage cells) and adipocytes (fat cells). Stromal cells are connective
tissue cells that form the supportive structure to bone .
Techniques used in Heart regeneration
Human Heart Regeneration
• Of the 4,000 Americans waiting for heart transplants, only 2,500 will receive new hearts in
the next year.
• The biggest risk is the their bodies will reject the new heart and launch a massive immune
reaction against the foreign cell,
• To combat the problems of organ shortage and decrease the chance that a patient's body will
reject it, researchers have been working to create synthetic organs from patients' own cells.
• A team of scientists from Massachusetts General Hospital and Harvard Medical School has
gotten one step closer, using adult skin cells to regenerate functional human heart tissue
• The scientists created a technique (Decellularization) in which they use a detergent
solution to strip a donor organ of cells that might set off an immune response in the
recipient.
• They stripped away many of the cells on 73 donor hearts that were deemed unfit for
transplantation.
• Then the researchers took adult skin cells and used a new technique with messenger RNA
to turn them into pluripotent stem cells (iPSC)
• After making sure the remaining matrix would provide a strong foundation for new cells,
the researchers put the induced cells into them.
• For two weeks they infused the hearts with a nutrient solution and allowed them to grow
under similar forces to those a heart would be subject to inside the human body.
Human Heart Regeneration
• After those two weeks, the hearts contained well-structured tissue that looked similar to
immature hearts
• In order to make that heart tissue to start beating , the researchers gave the hearts a shock of
electricity (defibrillation), which turned out to be successful .
• This is the closest researchers have come to their end goal in growing an entire working heart.
Problems
• To improve their yield of pluripotent stem cells (a whole heart would take tens of billions, one
researcher said in a press release)
• Find a way to help the cells mature more quickly, and perfecting the body-like conditions in
which the heart develops
Human Heart Regeneration
STEM CELLS IN KIDNEY REGENERATION
• Stem cells have the ability to repair injured organs and ameliorate damaged function.
The strategy for kidney tissue repair is the recruitment of stem cells and soluble
reparative factors to the kidney to elicit tissue repair and the induction of
dedifferentiation of resident renal cells.
• Kidney regeneration is a challenging but promising strategy aimed at reducing the
progression to end-stage renal disease (ESRD) and improving the quality of life of
patients with ESRD. Adult stem cells are multipotent stem cells that reside in various
tissues, such as bone marrow and adipose tissue.
Reasons that lead to kidney failure
• A blood clot in or around your kidneys.
• Infection.
• An overload of toxins from heavy metals.
• Drugs and alcohol.
• Vasculitis, an inflammation of blood vessels.
• Lupus, an autoimmune disease that can cause inflammation of
many body organs.
10 Signs You May Have Kidney Disease
• You're more tired, have less energy or are having trouble
concentrating. ...
• You're having trouble sleeping. ...
• You have dry and itchy skin. ...
• You feel the need to urinate more often. ...
• You see blood in your urine. ...
• Your urine is foamy. ...
• You're experiencing persistent puffiness around your eyes. ...
• Your ankles and feet are swollen.
Liver Transplant
• Over 8,000 liver transplants
are performed annually in the
U.S.
• Chronic liver diseases affect
more than 500 million people
worldwide and causes 2% of
all deaths.
• Cirrhosis anticipated to be the
12th leading cause of death in
2020.
• No noticeable increase in
liver donors.
Most patients in need
of a liver transplant
suffer from chronic
conditions
Hepatitis (swelling of
the liver) and Cirrhosis
(permanent scarring
of the liver)
can lead to Acute
Liver Failure
other causes of liver
failure
Ingestion of too many
toxins (alcohol)
Communicable
diseases
Some chemotherapy
medications
Current Treatment
• The first human liver transplant was performed by Thomas Starzyl in 1963
• Transplantation is now the preferred treatment for a failing/failed liver
• It is also possible to transplant just a piece of liver as an allograft
• Most transplants are done for patients with chronic liver diseases leading to cirrhosis
Current Technology
A variety of methods have been developed to improve or replace, at least temporarily, these have
included:
i. Bioartificial liver devices
ii. Cell therapy
BIO-ARTIFICIAL LIVER DEVICES
• Extracorporeal supportive device for an individual suffering from liver failure
• Contains both biological and manufactured components
• These devices bridge until the patient recover or receive a transplant
• BALs are essentially bioreactors, with embedded hepatocytes (liver cells) that perform the
functions of a normal liver.
• They process oxygenated blood plasma, which is separated from the other blood constituents.
• With this method there comes it disadvantage
• Lack of knowledge regarding metabolic functions
• Virus infection
• Seeding liver cells onto an extracellular matrix
(scaffold) made of porous biodegradable materials.
• This seeded shell is placed in either a static or
dynamic bioreactor in which the cells might grow,
proliferate and hopefully differentiate.
• Most ex vivo livers are currently used for researching
the functions of liver cells themselves
Cell Therapy
Limitations
• Not everything is known yet about how the liver works.
• How cells differentiate and organize themselves.
• What factors might help stimulate “natural” liver growth.
• Liver has high cell density.
• Liver contains specific cell sub-populations that are hard to artificially reproduce.
• Also difficult to artificially reproduce tiny capillaries, ducts, and pores
Future
• More highly developed scaffolds that incorporate the micro structures within the
liver.
• Complete production of functional human livers.
• Increased availability and affordability.
CONCLUSION
• Stem cells can be derived from adult, cord blood and embryonic stem cells.
• Stem cell transplantation can both support highly intensive chemotherapy
and promote highly effective immunotherapy.
• Recent advances in stem cell transplantation allow therapy more tailored to
disease and patient.
• Improved supportive care measures expand transplant to more patients.
• Human embryonic stem cell research is ethically and politically
controversial because it involves the destruction of human embryos.
• As a matter of religious faith and moral conviction many people believe
that “human life begins at conception” and that an embryo is there for a
person.
CONCLUSION
• According to this view, an embryo has interests and rights that must be
respected. From this perspective, taking a blastocyst and removing the inner
cell mass to derive an embryonic stem cell line is tantamount to murder.
• Stem cell is a very promising field which can be a successful to
conventional techniques like organ transplantation which requires donors.
But it is also still not successful because of the ethical issues involved and
the need of experiments carried upon human models
REFERENCES
• Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink
Falguni Pati1,*, Jinah Jang2,3,*, Dong-Heon Ha1, Sung Won Kim4,5, Jong-Won Rhie6, Jin-Hyung
Shim7,Deok-Ho Kim3,8,9&Dong-Woo Cho1
• An overview of tissue and whole organ decellularization processes
Peter M. Crapo, Thomas W. Gilbert, Stephen F. Badylak*McGowan Institute for Regenerative
Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA

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Stem cells for artificial organ regeneration

  • 2. INTRODUCTION A stem cell is a cell with the unique ability to develop into specialised cell types in the body. There are three main types of stem cell: • Embryonic stem cells • Adult stem cells • Induced pluripotent stem cells Regeneration means the regrowth of a damaged or missing organ part from the remaining tissue.
  • 3. ORGANS THAT CAN BE REGENERATED USING STEM CELL TECHNOLOGY Heart Liver Brain Bone Esophagus Kidney Stomach Lung
  • 4. 4 ECM + Stem cell Assay 3 Lyophilization 2 Decellularization 1 PROCEDURE FOR PREPARING BIOINK FOR 3D BIO PRINTING This process is used to isolate the extracellular matrix (ECM) of a tissue(SDS & NaCl is been used to remove the DNA content) It is basically a water removal process typically used to preserve perishable materials, to extend shelf life • DNA(< 2%) • GAG • Collagenase Adding the Stem Cell along with the ECM
  • 5. DIGRAMETIC REPRESENTATION Scaffolds are materials that have been engineered to cause desirable cellular interactions to contribute to the formation of new functional tissues for medical purposes. 1. Decellularized Tissue 2. Lyophilized Tissue 3. Assay 4. Organ Printing
  • 7. The various processes involved in the manufacturing of artificial organs involve the following: • Tissue Engineering: This is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions. • Bio-printing or 3D printing of tissues: Bio-printing, where living cells are precisely printed in a certain pattern, has great potential and promise for fabricating engineered living organs. • Industrially by using biomaterials which includes metals, ceramics, polymers and composites. • In the laboratory by using stem cells under Regenerative Medicine.
  • 8. • GRAFT: A viable tissue that after removal from a donor site is implanted with in a recipient tissue is then restored, repaired and regenerated. • GRAFTING: It is a procedure used to replace/restore missing bone or gum tissue. • BONE GRAFTS: The materials used for the replacement or augmentation of the bone. OSTEOINDUCTION Stimulation of osteoprogenitor cells Osteoblasts New Bone Formation BIOLOGICAL CONCEPTS IN BONE GRAFTING • Contains bone forming cells (osteogenesis) • Serve as scaffold for bone formation (osteoconduction) • Matrix of bone grafting material contains bone inductive substances (oteoinduction)
  • 9. OSTEOGENESIS Osteoblast s in the transplante d bone having adequate blood supply and cellular viability Forms new centre of ossificati on within the graft TYPES OF GRAFT TISSUE AUTOGRAPHS A tissue transferred from one position to another within the same individual. ALLOGRAPHS/HOMOGRAPHS Obtained from genetically dissimilar individual of same species. XENOGRAPHS/HETEROGRAPHS Tissue transferred from one species to another species ALLOPLASTS A synthetic graft or inert foreign body implanted into tissue.
  • 10. BONE CELLS ARE COMPOSED OF Osteoblasts Osteoclasts Osteiods Inorganic mineral sals BONE REGENERATION Bone regeneration is process which response to any injury like accidental fracture, development of continuous remodelling of bone, disease condition like osteoporosis and after surgery like arthoplasty, etc. Bone regeneration process involves certain processes like hematoma formation, callus formation, callus ossification and bone remodelling
  • 11. Need of Bone Regeneration There are over 15 million fracture cases globally and an estimated 2.2 million bone graft procedures are performed annually to promote fracture healing or to fill defects . Sometimes the common solutions, such as Autografts & Allografts are not suitable due to the donor site morbidity, disease transmissions, and, for the implants case, failure may occur after transplantation of tissue. Scaffolds Polymeric Natural Bone Morphogeni c Proteins Mesenc hymal cells and Growth Factors APPROCHES TO BONE REGENERATION
  • 12. MESENCHYMAL STEM CELLS Multipotent stromal cells that made up of different cell like: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells). Stromal cells are connective tissue cells that form the supportive structure to bone .
  • 13.
  • 14. Techniques used in Heart regeneration
  • 15. Human Heart Regeneration • Of the 4,000 Americans waiting for heart transplants, only 2,500 will receive new hearts in the next year. • The biggest risk is the their bodies will reject the new heart and launch a massive immune reaction against the foreign cell, • To combat the problems of organ shortage and decrease the chance that a patient's body will reject it, researchers have been working to create synthetic organs from patients' own cells. • A team of scientists from Massachusetts General Hospital and Harvard Medical School has gotten one step closer, using adult skin cells to regenerate functional human heart tissue
  • 16. • The scientists created a technique (Decellularization) in which they use a detergent solution to strip a donor organ of cells that might set off an immune response in the recipient. • They stripped away many of the cells on 73 donor hearts that were deemed unfit for transplantation. • Then the researchers took adult skin cells and used a new technique with messenger RNA to turn them into pluripotent stem cells (iPSC) • After making sure the remaining matrix would provide a strong foundation for new cells, the researchers put the induced cells into them. • For two weeks they infused the hearts with a nutrient solution and allowed them to grow under similar forces to those a heart would be subject to inside the human body.
  • 17. Human Heart Regeneration • After those two weeks, the hearts contained well-structured tissue that looked similar to immature hearts • In order to make that heart tissue to start beating , the researchers gave the hearts a shock of electricity (defibrillation), which turned out to be successful . • This is the closest researchers have come to their end goal in growing an entire working heart. Problems • To improve their yield of pluripotent stem cells (a whole heart would take tens of billions, one researcher said in a press release) • Find a way to help the cells mature more quickly, and perfecting the body-like conditions in which the heart develops
  • 19. STEM CELLS IN KIDNEY REGENERATION
  • 20. • Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. • Kidney regeneration is a challenging but promising strategy aimed at reducing the progression to end-stage renal disease (ESRD) and improving the quality of life of patients with ESRD. Adult stem cells are multipotent stem cells that reside in various tissues, such as bone marrow and adipose tissue.
  • 21.
  • 22. Reasons that lead to kidney failure • A blood clot in or around your kidneys. • Infection. • An overload of toxins from heavy metals. • Drugs and alcohol. • Vasculitis, an inflammation of blood vessels. • Lupus, an autoimmune disease that can cause inflammation of many body organs.
  • 23. 10 Signs You May Have Kidney Disease • You're more tired, have less energy or are having trouble concentrating. ... • You're having trouble sleeping. ... • You have dry and itchy skin. ... • You feel the need to urinate more often. ... • You see blood in your urine. ... • Your urine is foamy. ... • You're experiencing persistent puffiness around your eyes. ... • Your ankles and feet are swollen.
  • 25. • Over 8,000 liver transplants are performed annually in the U.S. • Chronic liver diseases affect more than 500 million people worldwide and causes 2% of all deaths. • Cirrhosis anticipated to be the 12th leading cause of death in 2020. • No noticeable increase in liver donors. Most patients in need of a liver transplant suffer from chronic conditions Hepatitis (swelling of the liver) and Cirrhosis (permanent scarring of the liver) can lead to Acute Liver Failure other causes of liver failure Ingestion of too many toxins (alcohol) Communicable diseases Some chemotherapy medications
  • 26. Current Treatment • The first human liver transplant was performed by Thomas Starzyl in 1963 • Transplantation is now the preferred treatment for a failing/failed liver • It is also possible to transplant just a piece of liver as an allograft • Most transplants are done for patients with chronic liver diseases leading to cirrhosis
  • 27. Current Technology A variety of methods have been developed to improve or replace, at least temporarily, these have included: i. Bioartificial liver devices ii. Cell therapy BIO-ARTIFICIAL LIVER DEVICES • Extracorporeal supportive device for an individual suffering from liver failure • Contains both biological and manufactured components • These devices bridge until the patient recover or receive a transplant • BALs are essentially bioreactors, with embedded hepatocytes (liver cells) that perform the functions of a normal liver. • They process oxygenated blood plasma, which is separated from the other blood constituents. • With this method there comes it disadvantage • Lack of knowledge regarding metabolic functions • Virus infection
  • 28. • Seeding liver cells onto an extracellular matrix (scaffold) made of porous biodegradable materials. • This seeded shell is placed in either a static or dynamic bioreactor in which the cells might grow, proliferate and hopefully differentiate. • Most ex vivo livers are currently used for researching the functions of liver cells themselves Cell Therapy
  • 29. Limitations • Not everything is known yet about how the liver works. • How cells differentiate and organize themselves. • What factors might help stimulate “natural” liver growth. • Liver has high cell density. • Liver contains specific cell sub-populations that are hard to artificially reproduce. • Also difficult to artificially reproduce tiny capillaries, ducts, and pores
  • 30. Future • More highly developed scaffolds that incorporate the micro structures within the liver. • Complete production of functional human livers. • Increased availability and affordability.
  • 31. CONCLUSION • Stem cells can be derived from adult, cord blood and embryonic stem cells. • Stem cell transplantation can both support highly intensive chemotherapy and promote highly effective immunotherapy. • Recent advances in stem cell transplantation allow therapy more tailored to disease and patient. • Improved supportive care measures expand transplant to more patients. • Human embryonic stem cell research is ethically and politically controversial because it involves the destruction of human embryos. • As a matter of religious faith and moral conviction many people believe that “human life begins at conception” and that an embryo is there for a person.
  • 32. CONCLUSION • According to this view, an embryo has interests and rights that must be respected. From this perspective, taking a blastocyst and removing the inner cell mass to derive an embryonic stem cell line is tantamount to murder. • Stem cell is a very promising field which can be a successful to conventional techniques like organ transplantation which requires donors. But it is also still not successful because of the ethical issues involved and the need of experiments carried upon human models
  • 33. REFERENCES • Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink Falguni Pati1,*, Jinah Jang2,3,*, Dong-Heon Ha1, Sung Won Kim4,5, Jong-Won Rhie6, Jin-Hyung Shim7,Deok-Ho Kim3,8,9&Dong-Woo Cho1 • An overview of tissue and whole organ decellularization processes Peter M. Crapo, Thomas W. Gilbert, Stephen F. Badylak*McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA