STEM CELL is a very famous topic these days. Due to lot of research work and debate on this topic, everybody wants to know about stem cells. Stem cells are the cells that can self-renew and also can differentiate into other cells types i.e. nerve cells, muscles cells etc. In body these cells replenish the loss of cells in different tissues and organs. On the basis of time of isolation, there are two major categories of stem cells, Embryonic Stem Cells (ESC) and Adult Stem Cells. ESC can proliferate rapidly and also maintain their pluripotency, so these are promising source in cell transplantation therapies for various diseases and injuries i.e. myocardial infarction, spinal cord injury, type-1 diabetes and few more, but there are two major hurdles in cellular therapy of ESC; i)- Ethical concerns due to use of Human embryos ii)- Tissue rejection after transplantation.
We can overcome these problems if we can generate pluripotent stem cells directly from somatic cells. In 1960, Prof. Gurdon and his colleagues successfully produced tadpoles by taking the nucleus from somatic cell of an adult frog and putting it into oocyte. Prof. Gurdon experiments proved the existence of pluripotency inducing factors. A similar experiment was done in 1997 and a famous clone “Dolly” was made.
In 2006, a big breakthrough in biomedical science came when first time Induced Pluripotent Stem Cells (iPSC) were generated from mice fibroblasts (mature cells) using four Transcription Factors (TF’s) and expressing them in mice fibroblasts using retroviral vectors. These TF’s include Oct4, Sox2, c-Myc and Klf4. The iPSC were very similar to ESC of mice in morphology, proliferation and teratoma formation. They also successfully produced mice chimera using iPSC. Recently iPSC were produced using only 3 TF’s (Oct4, Sox2 and Klf4). After fibroblasts iPSC were generated from mouse hepatocytes, pancreatic cells, epithelial cells, neuronal cells and B-lymphocytes. These results clearly indicate that iPSC can be induced in various somatic cells using few defined TF’s.
It is still unknown, how iPSC can be generated using only 3 TF’s. What we know so far is that these 3 TF’s causes the expression of pluripotency related gene and suppresses the expression of lineage-specific genes.
In 2007, first time human iPSC were generated from human fibroblasts using same four TF’s. In the same year another lab also successfully generated iPSC by using another combination of TF’s (Oct4, Sox2, Nanog and Lin28). There are many differences in mice and human ESC, so it was quite surprising for scientists that same set of TF’s can produce human iPSC.The generated human iPSC were very similar to Human Embryonic Stem Cells (hESC), both in proliferation and morphology as well as they expresses the same ESC markers (SSEA’s, TRA, Oct4, Nanog etc.). The generated iPSC can differentiate into all three germ layers (Ectoderm, Mesoderm and Endoderm), they form teratoma and has germline transmission competency. Additionally iPSC were also differentiated into Neurons and beating cardiomyocytes in vitro. Now many different labs in the world are generating disease specific (Parkinson, type 1 diabetes etc.) iPSC to better study the onset of disease and to develop disease models.
A big future application of iPSC technology is in the field of regenerative medicine. Patient specific iPSC will make it possible to treat the patient with his own cells without the problem of immune rejection. There are still some safety concerns because iPSC can form tumors in body (in vivo), so research work is underway to safely produce iPSC using integration free methods.
In short, iPSC technology will have enormous applications especially in the field of regenerative medicine. The concept of iPSC and its applications is very simple, just took the cells from the patient, grow them in culture dish, express ESC specific TF’s in these cells and reverse the cells from mature state to ESC level. One can differentiate these cells into any mature cell type of the body i.e. Neuronal cells, Beta cells of Islets, muscles cells etc.
iPSC technology is a big hope for millions of patients. There is no iPSC related work in Pakistan so far. This is the right time to start this research work in Pakistan so that millions’ of Pakistani patients could be treated from suffering of different diseases. Government and researchers must show a rapid response in this regard.
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