Regenerative medicine ; Its future in Modern Medical Science.

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 as a vehicle to treat disease and injury.

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.

It is believed that replacing damaged or malfunctioning cells with fully functional ones may be a useful therapeutic strategy in treating many of these diseases and conditions.

Introduction..

What are stem cells???

Stem cells are the cells which are able to self renew and differentiate into mature cells (potency).

Stem cells are cells that have the ability to branch out and change, or differentiate, into two or more different cell types, ability to develop into functional, differentiated cells.

In general, there are two broad categories of stem cells: adult stem cells and embryonic stem cells.

STEM CELL Types

Adult stem cells are derived from various tissues in the human body.

Because they can branch out into many different cell types, they are referred to as “multipotent.”

Embryonic stem cells, referred to as ES cells, which are derived from pre-implantation embryos, are unique because they are “pluripotent.”

It means that they can develop into all cells and tissues in the body, and they self-renew indefinitely in their undifferentiated state.

The “unavoidable” faces!!

1st to isolate embryonic stem

cell in lab.James Thomson

Shinya Yamanaka

1st to reprogramme cells to form

iPSCs

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.

Why opt for “Regeneration”??

The shortage of organs available for donation

Organ transplant rejection; These unlimited supplies of autologous cells like iPSCs could be used to generate transplants without the risk of immune rejection.

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“)

From 1995 to 1998 Michael D. West, PhD, Geron Corporation and its academic collaborators James Thomson at the University of Wisconsin-Madison and John Gearhart of Johns Hopkins University that led to the first isolation of human embryonic stem cells.

Dr. Anthony Atala

Pioneers and the idea behind “RM”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.)

Paolo Macchiarini

Pioneers and the idea behind “RM”

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.STEM CELLS

Induced pluripotent stem cells (also known as iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells.

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."

Induced pluripotent stem cells

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.

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

Oct-3/4

Myc

Sox

Potency of IPS Cells

The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) of the pre-implantation stage embryo, there has been much controversy surrounding their use.

Further, because embryonic stem cells can only be derived from embryos, it has so far not been feasible to create patient-matched embryonic stem cell lines.

Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line.

IPSC’s

Pros & Cons..

OR

Cell Therapy

Cells are then transplanted

into the patients.

Cells are isolated from donors or

other organisms

Isolated cells are cultured, further manipulated and

expanded.

It’s a in vivo treatment

Tissue Engineering

The “Future Prospects”

The futuristic application of regenerative medicine is

depicted diagrammatically(Andrews, Wyatt (2008-

02-07). "A "Holy Grail" Of Healing". Cbsnews.com. Retrieved 2010-03-19.)

Conclusion.. This field holds the promise of regenerating damaged tissues and

organs in the body by replacing damaged tissue or organ.

iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific basis of disease.

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.

Efforts to generate iPSCs accomplished the goal using retroviral vectors but now plasmids & adinoviruses are used reducing mutagenesis risks.

(Charles A. Goldthwaite, Jr., Ph.D. 2010)

1. French AJ, Adams CA, Anderson LS, Kitchen JR, Hughes MR, Wood SH. Development of human cloned blastocysts following somatic cell nuclear transfer (SCNT) with adult fibroblasts. Stem Cells. 2008;26:485-483.

2. Byrne JA, Pedersen DA, Clepper LL, et al. Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature. 2007;450:497-502.

3. Hurlbut WB. Ethics and embryonic stem cell research: altered nuclear transfer as a way forward. BioDrugs. 2007;21:79-83.

4. Meissner A, Jaenisch R. Generation of nuclear transfer-derived pluripotent ES cells from cloned Cdx2-deficient blastocysts. Nature. 2006;439:212-215

Bibliography..

I, want to express my sincere gratitude towards our honorable principal sir, Dr. AMIT CHAKRABARTY,our honorable vice principle Mrs. SUDIPA CHAKRABARTY & our other respected faculty members for helping me make the presentation enabling its successful completion. Last but hardly the least I would also like to thank my friends for their help & coordination without whose support accomplishing such a thing would not have been possible.

Acknowledgement.