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.”
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.