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Self-Renewing Hematopoietic Stem Cells: Major Game-changer In Blood Disorder Therapy
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Self-Renewing Hematopoietic Stem Cells: Major Game-changer In Blood Disorder Therapy

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Highlights:
  • For several inherited and acquired blood diseases, the only cure is bone marrow transplant from a genetically matched donor, which in many cases is not easy.
  • Current study has discovered a method of producing reprogrammed hematopoietic stem cells (HSC) in the lab.
  • Transplanting these engineered self renewing HSC can potentially cure several blood diseases.

Reprogrammed lab engineered HSC could be a game-changer in the treatment of several blood disorders such as leukemia, aplastic anemia and sickle cell anemia, according to ground breaking research conducted by scientists at Weill Cornell Medicine. This is a first-time achievement and if clinically feasible, could mark a paradigm shift in treatment approach to several blood diseases.

"This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases," added co-senior author Dr. Joseph Scandura, an associate professor of medicine and scientific director of the Silver Myeloproliferative Neoplasms Center at Weill Cornell Medicine.

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Generating Self-Renewing HSC: How the Weill Cornell Team Accomplished This Feat
  • The research team obtained vascular endothelial cells from mice and reprogrammed them to produce proteins that made them function like blood stem cells.
  • The cells thus produced were cultured in specially engineered vascular niche created for this purpose, where they grew and multiplied.
  • The lab grown HSCs were then transplanted as single cells with their daughter cells into mice whose marrow had been destroyed by irradiation. This was done to see whether the transplanted HSCs could self-renew and produce healthy blood cells.
  • To the delight of the team, these HSCs were able to grow and multiply in the transplanted environment and in fact regenerated the entire blood system of the mice, for their entire lifespan. This process is referred to as 'engraftment'.
  • These mice went on to live full normal lives without developing any leukemias or similar cancers.
"We developed a fully-functioning and long-lasting blood system," said lead author Dr. Raphael Lis, an instructor in medicine and reproductive medicine at Weill Cornell Medicine. In addition, the HSC-engrafted mice developed all of the working components of the immune systems. "This is clinically important because the reprogrammed cells could be transplanted to allow patients to fight infections after marrow transplants," Dr. Lis said.

Interestingly, the same team had earlier published their research where they demonstrated that it was possible to generate functional HSCs from adult vascular endothelial cells. Unfortunately, they were unable to prove that they had indeed produced authentic functional HSCs by demonstrating its self-renewing and functional capacity. The current study was hence done to address this issue.
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What are Hematopoietic Stem Cells (HSCs)? 

Hematopoietic stem cells are precursors of blood cells. They are capable of differentiating into all three blood cell types, namely red cells, white cells and platelets.

The red cells, white cells and platelets have a limited lifespan and are destroyed when they become senescent or after their functions are over. They have to be constantly replenished and this is where the HSCs step in and maintain adequate blood cell counts for the normal health and well-being of the individual.

In addition to the production of mature blood cells, the HSCs have a unique property. They can self-renew and form more of their kind such that a few thousand functional HSCs can ensure an adequate supply of all the blood cells that one needs.

Crucial Factor In Successful Generation of HSCs 

As stated earlier, the current research team demonstrated that adult vascular endothelial cells could be programmed to become hematopoietic stem cells.

The team also found that specialized types of endothelial cells provide a suitable nurturing environment for the HSCs, termed the 'vascular niche' and these cells are referred to as vascular niche cells. The regeneration and self-renewal proceeds without a hitch in that nurturing environment.

The crucial factor was obviously providing the right nurturing environment.

"We think the difference is the vascular niche," said contributing author Dr. Jason Butler, an assistant professor of regenerative medicine at Weill Cornell Medicine. "Growing stem cells in the vascular niche puts them back into context, where they come from and multiply. We think this is why we were able to get stem cells capable of self-renewing."

What Is The Scope of Generating Engineered HSC's? 

There are innumerable applications of functional HSCs. These include the following to name a few:
  • Use in persons needing a bone marrow transplant where a suitable donor cannot be identified.
  • Cure of cancers such as leukemias and myeloproliferative disorders.
  • Cure of genetic diseases such as sickle cell anemia.
  • Last but not the least, the concept of a 'nurturing environment or niche' can open up opportunities for future research into gaining insight into the secrets of stem cell's regenerative capacity, longevity and to generate stem cells for use in the clinical setting.
Reference :
  1. Raphael Lis, Charles C. Karrasch, Michael G. Poulos, Balvir Kunar, David Redmond, Jose G. Barcia Duran, Chaitanya R. Badwe, William Schachterle, Michael Ginsberg, Jenny Xiang, Arash Rafii Tabrizi, Koji Shido, Zev Rosenwaks, Olivier Elemento, Nancy A. Speck, Jason M. Butler, Joseph M. Scandura, Shahin Rafii. Conversion of adult endothelium to immunocompetent haematopoietic stem cells. Nature, 2017; DOI: 10.1038/nature22326
Source: Medindia

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