A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice.
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.
Lee
Ryang Hwa
RH
Center for Gene Therapy, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA.
Hsu
Shu Ching
SC
Munoz
James
J
Jung
Jin Sup
JS
Lee
Na Rea
NR
Pochampally
Radhika
R
Prockop
Darwin J
DJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D000073883:CX3C Chemokine Receptor 1; D049109:Cell Proliferation; D017690:Cell Transplantation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D006085:Graft Survival / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D015728:Receptors, HIV / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation
D000073883:CX3C Chemokine Receptor 1; D019718:Receptors, CXCR4; D018121:Receptors, Cytokine; D015728:Receptors, HIV