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Regenerative medicine.pptx

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Regenerative medicine.pptx

  1. 1. Regenerative medicine: Current therapies and future directions… •Presented By: •Param Jyoti Rana •Roll no-18MBC017 •PG 3rdSemester •Department of Biochemistry •Ravenshaw University
  2. 2. Contents: • Introduction. • What are stem cells??? • Different types of stem cell. • * Embryonic stem cells • * Adult stem cells • What is “REGENERATIVE MEDICINE”?? • Why opt for “Regeneration”?? • The “unavoidable” faces!! • Pioneers and the idea behind “RM” • Induced pluripotent stem cells. • * Responsible Genes !! Turning Somatic Cells into Pluripotent Stem Cells • Tissue Engineering. Stem cell in 3D Bioprinting… • THERAPIES IN THE MARKET. • Pros… & Cons… • Conclusion: • References
  3. 3. Introduction: • Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. • The emerging field of treatment called “regenerative medicine” or “cell therapy” refers to treatments that are founded on the concept of producing new cells to replace malfunctioning or damaged cells. • Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. • Regenerative medicine has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to normalize congenital defects. • Our focus is the development of effective methods to generate replacement cells from stem cells. • This is especially true of diseases associated with aging such as Alzheimer’s disease, Parkinson’s disease, type II diabetes, heart failure, osteoarthritis, and aging of the immune system, known as immunosencence.
  4. 4. What are stem cells??? • A stem cell is a cell with the unique ability to develop into specialised cell types in the body. In the future they may be used to replace cells and tissues that have been damaged or lost due to disease. • Our body is made up of many different types of cell. Most cells are specialised to perform particular functions, such as red blood cells that carry oxygen around our bodies in the blood, but they are unable to divide. • Stem cells provide have two unique properties that enable them to do this: 1.They can divide over and over again to produce new cells. 2. As they divide, they can change into the other types of cell that make up the body.
  5. 5. Different types of stem cell: • There are two main types of stem cell: • Embryonic stem cells. • Adult stem cells.
  6. 6. Embryonic stem cells: • Embryonic stem cells supply new cells for an embryo as it grows and develops into a baby. • These stem cells are said to be pluripotent, which means they can change into any cell in the body. Figure 1.2.Characteristics of Embryonic Stem Cells. (© 2006 Terese Winslow)
  7. 7. Adult stem cells: • Adult stem cells supply new cells as an organism grows and to replace cells that get damaged. • Adult stem cells are said to be multipotent, which means they can only change into some cells in the body, not any cell, for example: – Blood (or 'haematopoietic') stem cells can only replace the various types of cells in the blood. – Skin (or 'epithelial') stem cells provide the different types of cells that make up our skin and hair. Winslow, Terese, and Lydia Kibiuk
  8. 8. What is “REGENERATIVE MEDICINE”?? • Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore or establish normal function". First cells are isolated. Then the isolated cells are manipulated expanded and or organs are generated from reprogrammed cells. The modified cells are transplanted into patients.
  9. 9. Why opt for “Regeneration”?? • YESTERDAY: • Successful transplantation of bone, soft tissue, and corneas occurred early in the 20th century. • Real progress in organ transplantation began in 1954 with the first successful kidney transplant. • During the 1960s, successful transplantation of pancreas/kidney, liver, isolated pancreas and heart occurred. • Transplant surgery success continued into the 1980s with successful heart-lung, single lung, double lung, living-donor liver, and living-donor lung transplants. TODAY Approximately 500,000 Americans benefit from a transplant each year. As of August 2010, there were approximately 108,000 people on the waiting list for donor organs. Many of these individuals will die before a suitable organ can be found. Tissue-engineered skin has been used for skin replacement, temporary wound cover for burns, and treatment for diabetic leg and foot ulcers. Tissue-engineered bladder, derived from a patient’s own cells, can be grown outside the body and successfully transplanted. Tissue-engineered vascular grafts for heart bypass surgery and cardiovascular disease treatment are at the pre-clinical trial stage. TOMORROW By providing healthy, functional tissues and organs, regenerative medicine will improve the quality of life for individuals. Imagine a world where there is no donor organ shortage, where victims of spinal cord injuries can walk, and where weakened hearts are replaced. This is the long-term promise of regenerative medicine, a rapidly developing field with the potential to transform the treatment of human disease through the development of innovative new therapies that offer a faster, more complete recovery with significantly fewer side effects or risk of complications. Insulin-producing pancreatic islets could be regenerated in the body or grown in the laboratory and implanted, creating the potential for a cure for diabetes. Tissue-engineered heart muscle may be available to repair human hearts damaged by attack or disease. Materials Science meets Regenerative Medicine as “smart” biomaterials are being made that actively participate in, and orchestrate, the formation of functional tissue.
  10. 10. The “unavoidable” faces!! 1st to isolate embryonic stem cell in lab James Thomson 1st to reprogramme cells to form iPSCs Shinya Yamanaka ( Nobel Prize-winning stem cell researcher)
  11. 11. Pioneers and the idea behind “RM” • At the Wake Forest Institute for Regenerative Medicine, in North Carolina, Dr. Anthony Atala and his colleagues have successfully extracted muscle and bladder cells & cultured them in molds. • Within weeks, the cells in the molds began functioning as regular bladders which were then implanted back into the patients' bodies. • (-"Regenerative Medicine. NIH Fact sheet 092106.doc“) Dr. Anthony Atala
  12. 12. Pioneers and the idea behind “RM”(Contd…) • Dr.Stephen Badylak at the University of Pittsburgh, developed a process for scraping cells from the lining of a pig's bladder, decellularizing the tissue and then drying it to become a sheet or a powder. This cellular matrix powder was used to regrow the finger of Lee Spievak, who had severed half an inch of his finger after getting it caught in a propeller of a model plane. • (-Clout, Laura (2008-04-30). "'Pixie dust' helps man grow new finger". Telegraph.co.uk. Retrieved 2010-03-19.) • In June 2008, at the Hospital Clínic de Barcelona, Professor Paolo Macchiarini and his team, of the University of Barcelona, performed the first tissue engineered trachea (wind pipe) transplantation. • (-"Tissue-Engineered Trachea Transplant Is Adult Stem Cell Breakthrough".Scientificblogging.com. 2008-11-19. Retrieved 2010-03-19.) Professor Paolo Macchiarini Dr.Stephen Badylak
  13. 13. Pioneers and the idea behind “RM”(Contd…) • In 2013, Researchers have successfully reprogrammed adult cells in a living animal for the first time, creating stem cells that have the ability to grow into any tissue found in the body. Until now these stem cells, known as induced pluripotent stem(IPS) cells, have only ever been created in Petri dishes in the laboratory after being removed from the animal. • However, researchers at the Spanish National Cancer Research Centre in Madrid, Spain, were able to create these cells in the bodies of living mice.
  14. 14. Induced pluripotent stem cells: • Induced pluripotent stem cells, or ‘iPS cells’, are stem cells that scientists make in the laboratory. • ‘Induced’ means that they are made in the lab by taking normal adult cells, like skin or blood cells, and reprogramming them to become stem cells. • Just like embryonic stem cells, they are pluripotent so they can develop into any cell type. • The iPSC technology was pioneered by Shinya Yamanaka’s lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes could convert adult cells to pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent.
  15. 15. In the initial 2006 study, it was reported that only four transcription factors (Oct4, Sox2, Klf4, and c- Myc) were required to reprogram mouse fibroblasts (cells found in the skin and other connective tissue) to an embryonic stem cell–like state by forcing them to express genes important for maintaining the defining properties of ESCs.
  16. 16. Responsible Genes !! • Oct-3/4: it is one of the family of octamer ("Oct“) transcription factors, and plays a crucial role in maintaining pluripotency. • The absence of Oct-3/4 in Oct-3/4+ cells, such as blastomeres and embryonic stem cells, leads to spontaneous trophoblast differentiation. • Myc family: The Myc family of genes are proto-oncogenes implicated in cancer. • Sox family: The Sox family of genes is associated with maintaining pluripotency similar to Oct-3/4, although it is associated with multipotent and unipotent stem cells in contrast with Oct-3/4, which is exclusively expressed in pluripotent stem cells. • KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming.
  17. 17. Turning Somatic Cells into Pluripotent Stem Cells • In 2006, Kazutoshi Takahashi and Shinya Yamanaka established for the first time murine ES-like cell lines from mouse embryonic fibroblasts (MEFs) and skin fibroblasts by simply expressing four transcription factor genes encoding Oct4, Sox2, Klf4, and c-Myc (Figure 1) (Takahashi & Yamanaka 2006). • They called these somatic cell-derived cell lines induced pluripotent stem (iPS) cells. These iPS cell lines exhibit similar morphology and growth properties as ES cells and express ES cell-specific genes. Transplantation of iPS cells into immunodeficient mice resulted in the formation of germ-cell-tumor (teratoma)- containing tissues from all three germ layers, confirming the pluripotent potential of iPS cells. • However, there were two problems: the low efficiency of establishing iPS cell lines and some variations in gene expression profiling between iPS cells and ES cells. The latter issue raised the concern that cell reprogramming may be insufficient to restore full pluripotency in somatic cells as exhibited by ES cells.
  18. 18. Turning Somatic Cells into Pluripotent Stem Cells
  19. 19. Regenerative Medicine:Current Therapies
  20. 20. Tissue Engineering: • In order to achieve the goals stated above, a tissue-engineered construct or tissue- engineered medical product can only be prepared if the following three components are available: • 1. A scaffold or a cell carrier to house the cells and serve as their microenvironment. • 2. Appropriate cells to fill the empty scaffold and convert it into the target tissue • 3. Certain bioactive compounds (growth factors) to guide the cells in their attachment • to the scaffold or during their proliferation and differentiation. • Scaffold Forms: • The form of the scaffold is one of the most debated issues in the tissue engineering circles. Some researchers argue that the scaffold should not be anything more than a sponge or foam to allow the cells to modify it as they please, while others design the scaffolds meticulously to guide the cells toward forming the target tissue. The main types of forms are: • • Macroporous, foam or sponge • • Fibrous, random or oriented • • Lamellar or filmlike, with or without patterns or designs
  21. 21. Various 3D macroporous scaffold types. (a) Rapid prototyped (additive manufactured) , (b) wet spun, (c) lyophilized sponge , (d) fibrous, (e) lamellar, (f) channel. Cell seeding in scaffold
  22. 22. The Scaffold Material: • As any biomaterial, the scaffold material can be of synthetic or biological origin with the limitation that it should mainly be polymeric because resorbability is essential for a successful tissue engineering application. • The synthetic polymers used are generally condensation polymers such as polyesters (polylactides (PLA), polyhydroxyalkanoates (PHA), polyaminoacids, polyamides, and polyurethanes. Biological polymers are also quite frequently used in tissue engineering. • Among these are mainly polypeptides (collagen, gelatin, silk fibroin) and polysaccharides (chitosan, cellulose, hyaluronan) .
  23. 23. Growth Factors: • Growth factors are protein molecules that are involved in the regulation of cell division, differentiation, migration, and cell survival. • They are growth stimulators (mitogens) and inhibitors, act as chemotactic agents, and are involved in angiogenesis and apoptosis. • Growth factors are found in membrane- bound form. • The classical growth factor list is presented in Table 18.3.
  24. 24. Overview : The scheme for tissue engineering of meniscus
  25. 25. Stem cell in 3D Bioprinting… • 3D bio printing is the process of creating cell patterns in a confined space using 3D printing technologies. • 3D bio printing is the layer by layer method to deposit materials known as bioinks to create tissue like structure. • Currently, bioprinting can be used to print tissues and organs to help research drug and pills. • WHAT IS BIO INK??? • Bio inks are materials and it support the adhesion, proliferation, and differentiation of mammalian cells. • Bio ink material is made from living cells and it like a liquid form. • Bio ink filaments are often deposited at or below human body temperature and under mild condition to preserve bio ink printability. BIO -PRINTER
  26. 26. Components: Cells Hydrogels Bio- printer Bioprinted tissue or organs. Pre-processing Processing Post-Processing 3 –PHASES:
  27. 27. THERAPIES IN THE MARKET: • Since tissue engineering and regenerative medicine emerged as an industry about two decades ago, a number of therapies have received Food and Drug Administration (FDA) clearance or approval and are commercially available (Table 1). • (Table 1). Regenerative medicine: Current therapies and future directions Angelo S. Maoa,b and David J. Mooneya,b,1
  28. 28. Pros… Cons… The difficulty of obtaining stem cells and the long period of growth required before use. Unproven treatments often come with high rejection rates. Cost can be prohibitive for many patients Additional ethical issues regarding the creation of human tissues in a lab. Medical benefits such as regenerating organ tissue and therapeutic cell cloning May hold the answer to curing various diseases, including Alzheimer's, certain cancers and Parkinson's. Research potential for human cell growth and development to treat a variety of ailments Requires only a small number of cells because of the fast replication rate.
  29. 29. Conclusion: • Every 30 seconds a patient dies from diseases which could be treated with tissue replacement . A tissue engineering and regenerative medicine (TERM) approach could probably offer the definitive solution for children with congenital malformations, young soldiers disfigured in war and old people suffering from chronic invalidating diseases, which are burdening more and more heavily on world's national economies . • This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue or organ. • In particular, the gene c-Myc is known to promote tumor growth which would have negatively affected iPSC usefulness in transplantation therapies but now Glis1 TF is being used.
  30. 30. References: 1.Turning Somatic Cells into Pluripotent Stem Cells By: Jiing-Kuan Yee, Ph.D. (Dept. of Virology, Beckman Research Institute, City of Hope National Medical Center) © 2010 Nature Education Citation: Yee, J. (2010) Turning Somatic Cells into Pluripotent Stem Cells. Nature Education 3(9):25 2. Hasirci, V., & Hasirci, N. (2018). Tissue Engineering and Regenerative Medicine. Fundamentals of Biomaterials, 281– 302. doi:10.1007/978-1-4939-8856-3_18 3.3D bioprinting using stem cells, Pediatric Research volume83, pages223–231 (2018) Chin Siang Ong, Pooja Yesantharao, Chen Yu Huang, GunnarMattson, Joseph Boktor, Takuma Fukunishi, Huaitao Zhang& Narutoshi Hibino

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