Researchers from the Ichan School of Medicine have now transferred four genes into mouse fibroblast cells, which produced cells that resembled hematopoietic stem cells, producing new blood cells.
These findings provide a platform for future development of patient-specific stem/progenitor cells, and more differentiated blood products, for cell-replacement therapy.
Mount Sinai researchers screened a panel of 18 genetic factors for inducing blood-forming activity and identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6 as sufficient to generate blood vessel precursor cells with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1 and Prominin1 within a global endothelial transcription program.
"The cells that we grew in a petri dish are identical in gene expression to those found in the mouse embryo and could eventually generate colonies of mature blood cells," said the first author of the study, Carlos Filipe Pereira, PhD, Postdoctoral Fellow of Developmental and Regenerative Biology at the Icahn School of Medicine.
"The combination of gene factors that we used was not composed entirely of the most obvious or expected proteins. Many investigators have been trying to grow hematopoietic stem cells from embryonic stem cells, but this process has been problematic. Instead, we used mature mouse fibroblasts, picked the right combination of proteins, and it worked," said Ihor R. Lemischka, PhD, Professor of Developmental and Regenerative Biology, Pharmacology and Systems Therapeutics and Director of The Black Family Stem Cell Institute at The Mount Sinai Medical Center.
"This discovery is just the beginning of something new and exciting and can hopefully be used to identify a treatment for blood disorders," said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai and Executive Vice President for Academic Affairs at The Mount Sinai Medical Center.
According to Dr. Pereira, there is a critical shortage of suitable donors for blood stem cell transplants. Donors are currently necessary to meet the needs of patients suffering from blood diseases such as leukemia, aplastic anemia, lymphomas, multiple myeloma and immune deficiency disorders.
"Programming of hematopoietic stem cells represents an exciting alternative," said Pereira.
The study was published online in CELL STEM CELL.