New Method Of Hematopoietic Stem Cell Population Expansion Found

A new laboratory method allows the expansion of adult hematopoietic stem cells (HSCs) using the SALL4 gene. The method produced a 10,000-fold increase in HSCs derived from normal human bone marrow.

“Investigators have been trying to expand human HSCs for 30 years, but so far there have been only small incremental advances without clinically meaningful results,” says Dr.Yupo Ma, M.D., Ph.D. of the Stony Brook University School of Medicine . “We believe our findings are so different from others that this method could open the door to a process that expands HSCs and be used clinically.”

HSCs are rare cells capable of differentiating into all blood cell lineages. These cells are used in clinical procedures to treat various blood diseases, including leukemia and lymphoma, and are central to bone marrow transplantation. Only one in three patients in need of bone marrow transplantation are matched with a suitable donor, and thus many patients die before finding a match. The Stony Brook research team’s discovery of using SALL4, which produces a protein that stimulates HSCs to grow, may be a critical first step to finding a treatment based on the expansion of HSCs that could become one alternative to finding a matched donor.

The research team devised a way to transfer a stem cell gene (SALL4) into human bone marrow HSCs (CD34+ and CD38-) using a viral delivery system. Once the cells started producing the SALL4 protein, they were exposed to chemical agents known as cytokines, in order to mimic the environment of normal bone marrow.

No adverse effects were detected in animal models monitored for more than 12 months. Dr. Ma’s team was also able to eliminate the need for viral delivery of SALL4 by generating a novel recombinant (TAT-SALL4) protein, making it possible to translate their work into the clinical setting.

The team demonstrated that cells in the expanded population could replace and expand into bone marrow stem cells. The team then successfully transplanted cells from primary recipients and transplant them into a secondary recipient, and from the secondary recipient into a tertiary recipient.

Adapted from the Stony Brook School of Medicine announcement.