Within our bones lies a spongy, ribbon-like material called bone marrow. Bone marrow is home to several different populations of stem cells, but the star of the stem cell show in the bone marrow are the hematopoietic stem cells or blood-making stem cells. When a patient receives a bone marrow transplant these are the stem cells that are transferred, take up residence in the new bone marrow, and begin making new red and white blood cells for the patient. Because bone marrow is such a precious commodity from a clinical standpoint, finding a way to make more of it is essential.
A new report from scientists at Mt Sinai Hospital in New York suggest that the transfer of specific genes into skin fibroblasts can reprogram mature, adult cells into hematopoietic stem cells that look and function exactly like the ones normally found within our bone marrow.
A research team at the Icahn School of Medicine at Mount Sinai led by Kateri Moore screen a panel of 18 different genes for their ability to induce blood-forming activity when transfected into fibroblasts. Kateri and others discovered that a combination four different genes (GATA2, GFI1B, cFOS, and ETV6) is sufficient to generate blood vessel precursors with the subsequent appearance of hematopoietic stem cells. These cells expressed several known hematopoietic stem cell surface proteins (CD34, Sca1 and Prominin1/CD133).
“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 Carlos Filipe Pereira, first author of this paper and a postdoctoral research fellow in Moore’s laboratory.
The combination of gene factors that we used was not composed of the most obvious or expected proteins,” said Ihor Lemischka, a colleague of Dr. Moore at Mt. Sinai Hospital. “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, pick the right combination of proteins, and it worked.”
According to Pereira, there is a rather critical shortage of suitable donors for blood stem cells transplants. Bone marrow 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.
“Dr. Lemischka and I have been working together for over 20 years in the fields of hematopoiesis and stem cell biology,” said Kateri Moore. “It is truly exciting to be able to grow these blood forming cells in a culture dish and learn so much from them. We have already started applying this new approach to human cells and anticipate similar success.”