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Group creates ‘authentic’ HSCs from endothelial cells

Hematopoietic stem cells in the bone marrow

Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).

The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.

In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.

“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.

“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 Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.

Drs Scandura and Rafii and their colleagues described this research in Nature.

The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.

The cells were grown and multiplied in co-culture with an engineered vascular niche.

This produced HSCs that were transplanted into irradiated mice.

The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.

In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.

If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.

“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”

“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.” 

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Hematopoietic stem cells in the bone marrow

Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).

The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.

In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.

“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.

“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 Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.

Drs Scandura and Rafii and their colleagues described this research in Nature.

The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.

The cells were grown and multiplied in co-culture with an engineered vascular niche.

This produced HSCs that were transplanted into irradiated mice.

The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.

In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.

If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.

“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”

“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.” 

Hematopoietic stem cells in the bone marrow

Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).

The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.

In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.

“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.

“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 Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.

Drs Scandura and Rafii and their colleagues described this research in Nature.

The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.

The cells were grown and multiplied in co-culture with an engineered vascular niche.

This produced HSCs that were transplanted into irradiated mice.

The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.

In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.

If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.

“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”

“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.” 

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