- 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
- Transplanting these engineered self
renewing HSC can potentially cure several blood diseases.
Reprogrammed lab engineered HSC could be
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.
‘Transplant of engineered functional hematopoietic stem cells can potentially yield a lifelong supply of healthy blood cells to cure several diseases.’
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.
What are Hematopoietic
Stem Cells (HSCs)?
Hematopoietic stem cells are precursors of blood cells.
capable of differentiating into all three blood cell types, namely red cells, white cells and
The red cells, white cells and platelets
have a limited lifespan and are destroyed when they become senescent or after
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
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.
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
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
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.
- 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