Journal
STEM CELL REVIEWS AND REPORTS
Volume 12, Issue 1, Pages 121-128Publisher
SPRINGER
DOI: 10.1007/s12015-015-9625-5
Keywords
Stem cell homing; Adult stem cells; CXCR4; VLA-4; SDF-1; S1P; C1P; Extracellular nucleotides; Lipid rafts; Priming; Chemotaxis
Funding
- NIH [2R01 DK074720, R01HL112788]
- Stella and Henry Endowment
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Successful clinical outcomes from transplantation of hematopoietic stem cells (HSCs) depend upon efficient HSC homing to bone marrow (BM), subsequent engraftment, and, finally, BM repopulation. Homing of intravenously administered HSCs from peripheral blood (PB) through the circulation to the BM stem cell niches, which is the first critical step that precedes their engraftment, is enforced by chemotactic factors released in the BM microenvironment that chemoattract HSCs. These chemotactic factors include alpha-chemokine stromal-derived factor 1 (SDF-1), the bioactive phosphosphingolipids sphingosine-1-phosphate (S1P) and ceramid-1-phosphate (C1P), and the extracellular nucleotides ATP and UTP. Stem cells may also respond to a Ca2+ or H+ gradient by employing calcium-or proton-sensing receptors, respectively. In this review, we will present emerging strategies based on ex vivo manipulation of graft HSCs that are aimed at enhancing the responsiveness of HSCs to BM-secreted chemoattractants and/or promoting HSC adhesion and seeding efficiency in the BM microenvironment.
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