title: Emerging Strategies to Enhance Homing and Engraftment of Hematopoietic Stem Cells.
abstract: 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 α-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 Ca(2+) 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.
authors.affiliation: Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA. mzrata01@louisville.edu.|Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland. mzrata01@louisville.edu.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.affiliation: Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.|Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Malwina
authors.initials: M
authors.lastname: Suszynska
mesh_terms: D000255:Adenosine Triphosphate / Q000819:agonists / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D002518:Ceramides / Q000819:agonists / Q000276:immunology / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000819:agonists / Q000276:immunology / Q000494:pharmacology; D002630:Chemotactic Factors / Q000819:agonists / Q000276:immunology / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D015232:Dinoprostone / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008246:Lysophospholipids / Q000819:agonists / Q000276:immunology / Q000494:pharmacology; D021962:Membrane Microdomains / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000819:agonists / Q000235:genetics / Q000276:immunology; D013110:Sphingosine / Q000819:agonists / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D055153:Stem Cell Niche / Q000187:drug effects* / Q000276:immunology; D014544:Uridine Triphosphate / Q000819:agonists / Q000276:immunology; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D002518:Ceramides; D054377:Chemokine CXCL12; D002630:Chemotactic Factors; D008246:Lysophospholipids; D019718:Receptors, CXCR4; C065576:ceramide 1-phosphate; C060506:sphingosine 1-phosphate; D014635:Valproic Acid; D000255:Adenosine Triphosphate; D015232:Dinoprostone; D013110:Sphingosine; D014544:Uridine Triphosphate
keywords: Adult stem cells; C1P; CXCR4; Chemotaxis; Extracellular nucleotides; Lipid rafts; Priming; S1P; SDF-1; Stem cell homing; VLA-4