For HSC, Location Matters

Harvesting hematopoietic stem cells (HSC) from the ends of bone—the trabecular area—yields a wealth of cells with superior regenerative and self-renewing abilities, according to research published in August (Cell Stem Cell 2013;13:175–89).

“It's similar to a bottle of milk—if you want the cream, you skim it off the top,” says study lead author Mickie Bhatia, PhD, professor and scientific director of the McMaster Stem Cell and Cancer Research Institute in Hamilton, Ontario, Canada.

Bhatia's team harvested cells from distinct areas of bone from humans and immunodeficient mice engrafted with human HSCs. Compared with the long bone area, trabecular bone contained higher numbers of HSCs, but the HSCs from both the human and the mouse samples had different molecular and functional characteristics. Among the functional differences between cells from the two locations, transplants done in mice showed that stem cells from trabecular bone had a greater ability to engraft in the marrow of the recipient. One likely reason: Bone-forming osteoblasts in the trabecular area exhibit higher expression of Notch, a protein thought to be important for stem cell renewal. (Osteoblasts play a key role in regulating HSCs in bone marrow.)

“This paper shows that the best stem cells like to live near trabecular bone surfaces, close to the bone cortex, instead of in endosteal regions in the long bones or deep within the bone marrow space, near blood vessels,” says Edmund Waller, MD, PhD, associate director of the Bone Marrow and Stem Cell Transplantation Center at Emory University's Winship Cancer Institute in Atlanta, GA, who was not involved in the research. “If you think of stem cells as the seeds and the bone as the soil, the trabecular bone provides the most fertile soil,” he says.

Pending further validation, Bhatia's findings might affect how surgeons harvest HSCs for transplants, says Waller. “If you put a needle into someone's hip to draw out stem cells, you may want to collect cells just after you go through the bone's hard cortical surface, rather than extracting them from deep within the bone,” he says.

When considered with a 2012 New England Journal of Medicine paper, these findings might further encourage transplants of HSCs from bone rather than from peripheral blood, which is currently the most common source for U.S. procedures. Last year, a multicenter, randomized trial comparing HSCs from peripheral blood with those from bone marrow from unrelated donors to treat leukemia and related diseases found similar survival rates after 2 years (N Engl J Med 2012;367:1487–96). Although peripheral-blood HSCs had a lower risk of graft failure, they conferred a significantly higher risk of chronic graft-versus-host disease, which can be extremely debilitating, notes Waller, possibly causing the recent slight shift in preference among some doctors for HSCs taken from bone marrow.

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