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Mature blood cells into blood-forming stem cells

Harvard Stem Cell Institute researchers at Boston Children’s Hospital have reprogrammed mature blood cells from mice into blood-forming hematopoietic stem cells (HSCs) using a cocktail of eight genetic switches called transcription factors.

The reprogrammed cells, which the researchers have dubbed induced HSCs (iHSCs), have the functional hallmarks of HSCs, are able to self-renew like HSCs, and can give rise to all of the cellular components of the blood like HSCs.

The findings mark a significant step toward one of the most sought-after goals of regenerative medicine: the ability to produce HSCs suitable for transplantation using more mature or differentiated cells.

Blood stem cell transplants (also known as bone marrow transplants) have been saving the lives of patients for almost three decades, but have been limited by the difficulty of obtaining good cell matches for transplantation.

The work, reported online in the journal Cell, was led by Harvard Stem Cell Institute Principal Faculty member Derrick J. Rossi, PhD, of Boston Children’s Program in Cellular and Molecular Medicine.

HSCs are the basic starting material for all blood stem cell transplants, regardless of their source (bone marrow, umbilical cord blood, peripheral blood). The success of any individual patient’s transplant correlates with the number of HSCs available for transplant: the more cells, the more likely the transplant will take hold. However, HSCs are quite rare(…)

“Blood cell production invariably goes in one direction: from stem cells, to progenitors, to mature effector cells,” Rossi explained. “We wanted to reverse the process and derive HSCs from differentiated blood cells using transcription factors that we found were specific to HSCs”(…)

Harvard Stem Cell Institute Principal; Faculty member Stuart Orkin, MD, one of the leaders of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and a co-author on the paper, noted that the use of mice as a kind of reactor for reprogramming marks a novel direction in HSC research(…)

More:hsci.harvard.edu/news/scientists-revert-mature-blood-cells-blood-forming-stem-cells