Building blocks of life

INTRODUCTION

Therapeutics, a field that focuses on resisting the challenges that our body faces, has been growing since its discovery and has managed to come to a point where mankind is not only able to defend but cope up with the upcoming diseases.


Cell based therapy is one such technique that aims to eradicate the challenges by incorporation of cells into our body.


THE BIRTH OF STEM CELLS

Stem cells include cells with immense capacity for self renewal and differentiation.

FIGURE 01- Types of stem cells

Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 1-22.


This phenomenal discovery came to life in the nineteenth century by the hands of Charles-Édouard Brown-Séquard. Born in 1817, this Mauritian scientist's claim of insertion of fluid caused scientists all around the world to study the organ secretions eventually leading to the invention of organotherapy.


Paul Niehans known as the father of cell therapy was interested in the cells ability to adapt. His curiosity of how cells functioned led him to inject cell extracts into a woman's body that led her to recover from a life threatening situation giving birth to cell therapy.


The idea of cell therapy had been implanted into the minds of young scientists but what remained was the development of the idea and defining of its limitations. This was done in the 1960's by two scientists from Canada Ernest McCulloch and James Till. They used X-rays as a means of inducing mutations into the mice.


They further worked on the irradiated mice to discover the Colony forming units which were the cells that resided in the spleen of the mice and termed it as CFU-S. After 30 years the discovery of Hematopoietic stem cells and their successful discovery took place. This was a desirable addition to what one day could be used to save lives.


In 2006, came the mind blowing discovery by Kazutoshi Takahashi and Shinya Yamanaka where they reprogrammed mice fibroblast cells which are multipotent stem cells in order to create pluripotent cells.These cells were later on termed as iPSC. This gave us an alternative to embryonic cells which had a lot of ethical issues being raised against.


FIGURE 02- Derivation of cells

Source: Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 1-22.


Shinya Yamanaka also succeeded in identifying the genes that played the role of the determining factor of the cells ability to replicate. This experiment was later on induced in humans as well. Here started the limitless applications of cells in clinical therapy.


APPLICATIONS

Cell based therapy can be defined as using cells as a means to strengthen and widen the horizon of the boundaries set by our immune system.


Cell based therapies include various means to incorporate cells into the living system. This could also be done by transforming one's own cells. Here we limit ourselves to the use of stem cells in cell therapy.


Cells are capable of replicating countlessly but as they are assigned functions in our body their genes that are required by our body are activated while the ones not required are shut down. These genes might include the ones that allow them to replicate endlessly. As we saw in the Yamanaka experiment, teratoma formation by inducing pluripotency into our cells can lead to the formation of our desired cells in future.


FIGURE 03- Therapeutic approaches

Source: Cellular Therapies Program - Dana-Farber Cancer Institute | Boston, MA


This technique can further be applied in therapeutics some of which include:

  1. Anti-cancer therapy :

Amongst the countless hopes this therapy carries, amongst the most famous applications include the use of these cells in cancer associated therapeutics.


FIGURE 04 - Anti-cancer Therapy

Source: Watt, F. M., & Driskell, R. R. (2010). The therapeutic potential of stem cells. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1537), 155-163.


2. Neurodegenerative disorders :


Stem cells called Mesenchymal stem cells have been known for their capacity to differentiate into nervous cells and also have a role in controlling the behaviour of our immune system. This capacity enables us to hypothesize the possibility of incorporating these cells in order to cure diseases like Parkinson’s, Alzheimer’s etc.


3.Hematopoietic stem cell transfer or bone marrow transplant :


This is an age-old technique still being used which sheds light on the theory that stem cells can actually be used in therapeutics giving hope for further methodologies for being developed.

FIGURE 05- HSCT Transplant methodologies

Source: Chabannon, C., Kuball, J., Bondanza, A., Dazzi, F., Pedrazzoli, P., Toubert, A., ... & Bonini, C. (2018). Hematopoietic stem cell transplantation in its 60s: A platform for cellular therapies. Science translational medicine, 10(436).


4. Development of grafts :


There are several companies dedicated to deriving epidermal grafts in labs for use in the case of an implant. This although costly will give us an opportunity to ease the clinical procedures in future.


Apart from that countless other applications have either been achieved or are being derived in the lab so as to use the knowledge we hold regarding the stem cells to its full potential.




FIGURE 06- Culturing stem cells (1)

Source: Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 1-22.




FIGURE 07- Culturing stem cells (2)

Source: Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 1-22.


LIMITATIONS

Despite the fact that cell therapies hold promise to cure a lot of diseases there are still ethical issues which are raised against their use in therapeutics.

Apart from that, the immune system plays an important role in determining whether or not our body can successfully accept the implants. There are still clinical trials pending for several applications either because of budgetary restrictions or due to the lack of equipment.


However, the promise that the cells have shown us with the developing world by proving itself to be effective in several cases gives us hope that one day it will be the cure to all the challenges that we face now.


- Akanksha Damani

Department of Biochemistry and biotechnology

St. Xaviers College Ahmedabad


REFERENCES
  1. Choumerianou, D. M., Dimitriou, H., & Kalmanti, M. (2008). Stem cells: promises versus limitations. Tissue engineering. Part B, Reviews, 14(1), 53–60.

  2. Watt, F. M., & Driskell, R. R. (2010). The therapeutic potential of stem cells. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1537), 155-163.

  3. Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 1-22.

  4. Brown-Séquard's experiments with organ extract set the stage for hormone therapy

  5. Cellular Therapies Program - Dana-Farber Cancer Institute | Boston, MA

  6. Alternative Stem Cell Sources

  7. Lees, J. S., Sena, E. S., Egan, K. J., Antonic, A., Koblar, S. A., Howells, D. W., & Macleod, M. R. (2012). Stem Cell-Based Therapy for Experimental Stroke: A Systematic Review and Meta-Analysis. International Journal of Stroke, 7(7), 582–588. Stem Cell-Based Therapy for Experimental Stroke: A Systematic Review and Meta-Analysis - Jennifer S. Lees, Emily S. Sena, Kieren J. Egan, Ana Antonic, Simon A. Koblar, David W. Howells, Malcolm R. Macleod, 2012

  8. The father of cell therapy

  9. Sharkis, S. J. (2005). Canadian stem cell scientists take the prize. Cell, 122(6), 817-819.

  10. Becker, A. J., McCulloch, E. A., & Till, J. E. (1963). Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells.

  11. Shinya Yamanaka - Facts - NobelPrize.org


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