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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2153-2161.
Prepublished online as a Blood First Edition Paper on November 8, 2005; DOI 10.1182/blood-2005-07-2701.


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STEM CELLS IN HEMATOLOGY

A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice

Ryang Hwa Lee, Shu Ching Hsu, James Munoz, Jin Sup Jung, Na Rea Lee, Radhika Pochampally, and Darwin J. Prockop

From the Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA; and the Department of Physiology, College of Medicine, Pusan National University, Pusan, Republic of Korea.

Controversies have arisen as to whether adult stem cells or progenitor cells from bone marrow can engraft into nonhematopoietic tissues in vivo. To resolve some of the controversies, we developed a highly sensitive polymerase chain reaction-based single nucleotide polymorphism (PCR-SNP) assay for competitive engraftment of mixtures of stem/progenitor cells. We used the assay to follow engraftment in immunodeficient mice of subpopulations of the stem/progenitor cells from human bone marrow referred to as either mesenchymal stem cells or marrow stromal cells (MSCs). The engraftment into adult mice without induced tissue injury was low and variable, but there was preferential engraftment of a subpopulation of rapidly self-renewing MSCs (RS-MSCs) compared with a subpopulation of slowly renewing MSCs (SR-MSCs). After intravenous infusion, there was a tendency for the cells to engraft into the hippocampal region that was previously designated a "vascular niche." Migration assays suggested that preferential engraftment of RS-MSCs was in part explained by their expression of CXCR4 and CX3R1, the receptors for SDF-1 and fractalkine.


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