University of Pittsburgh Researchers Culture Blood-Forming Stem Cells from Human Fat Tissue
Researchers at the University of Pittsburgh School of Medicine have successfully isolated and cultured human hematopoietic stem cells from fat, or adipose, tissue, suggesting that they have found another important source of cells for reconstituting the bone marrow of patients undergoing intensive radiation therapy for blood cancers. They are presenting this ground-breaking research at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) North American Chapter meeting being held June 13 to 16 at the Westin Harbor Castle conference center in Toronto.
Adipose tissue has the ability to rapidly expand or contract in accordance with nutritional constraints. In so doing, it requires rapid adjustment in its blood supply and supporting connective tissue, or stroma. Based on previous reports that the “stromal vascular” fraction of adipose tissue contains stem cells that give rise to pericytes — cells surrounding small blood vessels — the University of Pittsburgh School of Medicine researchers, led by Albert D. Donnenberg, Ph.D., professor and director of the Hematopoietic Stem Cell Laboratory, University of Pittsburgh Cancer Institute, isolated the stromal vascular fraction from human adipose tissue and expanded these cells by growing them in a specialized blood-culturing medium for 21 to 42 days.
Using a cell-sorting method known as flow cytometry, the researchers detected a broad spectrum of blood-forming, or hematopoietic, cells among the cultured cells at varying stages of differentiation. In particular, they observed both early and mature red blood cells. Moreover, they detected CD34+ cells at approximately the same frequency as is present in freshly isolated bone marrow. In bone marrow, CD34+ expression indicates the presence of progenitor cells which give rise to all of the different types of blood cells.
These data indicate that hematopoietic stem cells, or cells that give rise to them, are an integral part of normal adipose tissue, according to Dr. Donnenberg. “We took cells from the stromal vascular fraction of normal adipose tissue and basically gave them bone marrow food to see what would happen. We were able to culture a variety of hematopoietic cells, including blood progenitor cells.”
Dr. Donnenberg said that the use of a patient’s own bone marrow or blood-derived stem cells for bone marrow reconstitution carries some risk that these cells are contaminated with the patient’s own tumor cells. “Since it has been shown in some cases that tumor cells contaminating bone marrow grafts are the source of recurrent malignancies after autologous transplantation, this might be a way of giving patients who need bone marrow reconstitution their own hematopoietic cells derived from a source other than their defective bone marrow,” he explained.
In addition to Dr. Donnenberg, J. Peter Rubin, M.D., department of surgery, University of Pittsburgh School of Medicine, was a key co-investigator along with other department of surgery researchers, Vera Donnenberg, Ph.D., Kacey Marra, Ph.D., and Bret Schipper, M.D.
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