brand-new role in the body! For example, we can now convert skin into blood, brain, liver and so on- the possibilities are endless. Ever since the successful culture of human embryonic stem cells, the scientific community has worked towards repairing of the damaged tissue or create new organs.
The grand journey of regenerative medicine began in 1962 when John B. Gurdon observed that specialization of egg cells in frogs was reversible. In 1981, embryonic stem cells were identified. This led to the creation of Dolly, the sheep in 1997 and isolation of human embryonic stem cells the following year.
The stem cell research received a major boost in 2006 when Shinya Yamanaka reported conversion of mouse fibroblasts into pluripotent stem cells using a combination of four transcription factors( Myc, Oct3 / 4, Sox2 and Klf4). These pluripotent cells were named iPS( induced Pluripotent Stem) cells for which in 2012 Dr Yamanaka and Dr John B. Gurdon jointly won a Nobel Prize in Physiology or Medicine.
How do stem cells decide their fate?
It is now recognized that immortality is not a background‘ constant’ but a‘ selectively operational’ phenomenon of stem cells. Just like the army advertises the requirement of new cadets, the stem cell microenvironment‘ broadcasts’ requirement for new stem cells. The‘ microenvironment’ is a systematic network buzzing with intricately woven circuits of stromal and stem cells. The circuits are highly sophisticated to ensure an effective cell-tocell communication. Just like an engine on a railway track follows a specific route, the secretory molecules march along their specific circuits conveying the message from one cell to another and vice versa.
Depending upon the cellular‘ orders received’, stem cells either generate more stem cells or a blend of‘ stem cells and differentiated cells’ through a process known as‘ stem cell fate decision’. The process is so sophisticated and so finely orchestrated that even a small deviation is sufficient to create havoc, and manifest as a disease.
Thus, the key challenge is to understand how stem cells
The key challenge is to understand how stem cells decide their fate? How do they figure out their future avatar? Despite decades of amazing research, the understanding of stem cell fate determination is far from complete
decide their fate? How do they figure out their future avatar? Despite decades of amazing research, the understanding of stem cell fate determination is far from complete.
It is unclear if the cells differentiate toward a particular fate as a result of intrinsic or extrinsic signals. Some scientists claim that stem cells have‘ deterministic’ elements and that their fate is determined by external factors that activate or repress specific genetic elements and networks.
The stochastic school of thought however supports the intrinsic route and proposes a differential expression of stem cell specific genes as a function of their evolution from a metastable state to a more stable state.
To understand this complex process better, perhaps an analogy may help. Consider a child as a naïve stem cell, trying to carve out its fate. The deterministic elements are the external factors in the form friends, colleagues, teachers and so on. The stochastic element is genetic elements inherited from parents. Whether a child turns out into a lawyer, sportsman, businessman and so on is determined by a combination of external influences and her / his intrinsic response to the external influence. Likewise, the stem cell fate determination is an outcome of dynamics of, not so well understood, extrinsic and intrinsic factors.
The discovery of stem cells has triggered imagination of stem cell therapy for a long time now. Of many developments in stem cell therapy, bone marrow transplantation has been the most exciting and most successful stem cell therapy. Haematopoietic stem cells are the oldest and the best studied stem cells. It has been more than 60 years, since the first experiments that led to the wide spread application of hematopoietic stem cell transplantation took place. Most early transplantations, especially done in atomic era used marrow as the source of stem cells; however the engrafted marrow cells mounted an
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