iPSCs: Secret to Regeneration

With the advent of the Yamanaka factors, it became possible to regenerate the damaged cells or tissue in adults which was impossible previously. This research area is fascinating for the numerous possibilities of regeneration it holds. Let’s have a broad view on this technology having vast scope in the future.

• What are iPSCs?

  “iPSCs” stand for induced pluripotent stem cells. First of all, stem cells are the cells in our body having the ability to repair, renew and regeneration. They are classified based on their potency as totipotent, pluripotent, multipotent and unipotent. Totipotent stem cell can form whole organism from a single cell, from embryonic and extra-embryonic (placental) tissues of developing embryo. Best example of a totipotent cell is a zygote. Pluripotent stem cell can give rise to all cells and different tissues of the body from the three germ layers (endoderm, mesoderm and ectoderm), but not the extra-embryonic tissues. Zygote after certain stages of cleavage (blastocyst stage) consists of the cells termed as embryonic stem cells derived from inner cell mass (ICM) that are pluripotent. Multipotent stem cell have restricted differentiation potential to certain types of cells of a specific lineage. Hematopoietic stem cell that forms all the types of blood cells like RBCs, WBCs, Platelets, etc. are multipotent in origin. Unipotent stem cell produces a single type of cell like gametes — sperm in male and ovum in female.

  Coming back to iPSCs, these are pluripotent stem cells from the term itself but the pluripotency is induced that we will be discussing in the further sections. So, iPSCs are the cells like embryonic stem cells.

  

  
  

• Technology behind iPSCs

  Due to lethal and ethical issues of embryonic stem cells, their use is banned in some countries. It’s like killing an embryo for the sake of benefit. Because, when we isolate some cells from embryonic stem cells, there is risk of damaging the developing embryo. Also, these cells are oncogenic (cancer causing) or tumorigenic (producing tumors) as they are not from the same body and due to uncontrolled proliferation.

  To surpass these hurdles, the research was carried out to convert any adult human cell to embryonic-like stem cells and iPSCs are the result of this. By using transcription factors called as Yamanaka factors (named behind the discoverer), this conversion is possible to achieve a meaningful regeneration. Transcription factors are the proteins that bind to DNA and initiate the gene expression. Yamanaka factors are OSKM — Oct4, Sox2, Klf4, c-Myc. Reprogramming of mature, specialized adult cells like fibroblasts (skin cells) to induced pluripotent stem cells (iPSCs) that has the capacity to repair damage in cells or tissues leading to their renewal and regeneration. But yes, proper regulation of their differentiation into their respective lineage becomes necessary at the same time. Otherwise, it can lead to oncogenesis or tumor formation too.

  To specify about the transcription factors, Oct4 and Sox2 are the main pluripotency genes, Klf4 promote cell proliferation and prevent cell death, whereas, c-Myc is responsible for loosening chromatin to access the DNA within it specifically.

  

• Applications & Future

  Applications of iPSCs are largely limited to stem cell therapy combined with gene therapy. This area of research has vast scope to treat variety of cancers, reverse neurological diseases and cure rare genetic disorders that was impossible before. Modelling of diseases in-vitro with the help of iPSCs and design appropriate strategies to correct it is one major area. To add on, testing the drugs available on them to recognize the target receptors. Also, the concept of organoids i.e. formation of organ-like arrangement of cells and tissues in-vitro using iPSCs and their accurate differentiation for assessment of repair, renewal and regeneration to achieve long term clinical benefit is also done. The most interesting is combining iPSCs with crispr-cas9 (read previous blog to know more about it) to correct genetic mutations in cells and their differentiation into the specific lineage for achieving normal cell regeneration. Extensive research in this area will unfold many scientific facts that can provide fruitful applications in future.

These were just seen on papers few years back but at the present time, there are lot of clinical studies coming out from various countries where actual benefits are seen combining theories and on-ground practice giving rise to a field known as translational research where research not just limits to lab bench but also to bedside in the clinics or hospitals (bench to bedside).

To conclude, the science of iPSCs opened doors for the cell and tissue regeneration that were closed. Not only cells and tissues, even regeneration of organs is possible because of iPSCs. This is how the science is fascinating us more and more day by day to find out the solutions to the unanswered questions and resolve the mysteries in biology.