Pleiotrophin Stimulates Expansion of Cord Blood Stem Cell Cultures

Researchers have identified a growth factor that stimulates the expansion of stem cell cultures from cord blood and that may make populations of such cells useful for treatment of patients lacking the cellular machinery --due to chemotherapy or radiation treatment, for example--for production of blood cells.

Investigators at Duke University (Durham, NC, USA) worked with a growth factor called pleiotrophin. This growth factor is known by several other names including Neurite Growth-promoting Factor 1 (NEGF1), Heparin Affin Regulatory Peptide (HARP), or Heparin Binding Growth associated molecule (HB-GAM). It is an 18-kDa molecular weight growth factor that has a high affinity for heparin. During embryonic and early postnatal development, pleiotrophin is expressed in the central and peripheral nervous system and also in several nonneural tissues, notably lung, kidney, gut, and bone.

In the current study, the investigators treated mouse bone marrow hematopoietic stem cells (HSCs) with pleiotrophin. They also treated cultures of human cord blood cells with the growth factor as well as administrating it in a systemic fashion to irradiated mice.

Results published in the March 21, 2010, online edition of the journal Nature Medicine revealed that pleiotrophin stimulated a ten-fold expansion of mouse bone marrow stem cells. Treatment of human cord blood cultures resulted in substantially increased severe combined immunodeficient (SCID)-repopulating cell counts as compared to input and cytokine-treated cultures. Systemic administration of pleiotrophin to irradiated mice caused a pronounced expansion of bone marrow stem and progenitor cells, indicating that pleiotrophin was a regenerative growth factor for HSCs. So far, there has been no evidence that use of pleiotrophin could trigger formation of cancer cells, since the investigators have not seen any evidence of cancer in mice up to six months after treatment with pleiotrophin.

"These results confirmed that pleiotrophin induces stem cell regeneration following injury,” said senior author Dr. John Chute, professor of cell biology at Duke University. "Perhaps more importantly, systemic treatment with pleiotrophin may have the potential to accelerate recovery of the blood and immune system in patients undergoing chemotherapy or radiotherapy. At this point, any progress we can make that helps us better understand which biological pathways are activated in stem cells in response to pleiotrophin will help move the discovery forward.”

Related Links:
Duke University