Emerging Strategies to Enhance Homing and Engraftment of Hematopoietic Stem Cells

Stem Cell Rev Rep. 2016 Feb;12(1):121-8. doi: 10.1007/s12015-015-9625-5.

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.

Keywords: Adult stem cells; C1P; CXCR4; Chemotaxis; Extracellular nucleotides; Lipid rafts; Priming; S1P; SDF-1; Stem cell homing; VLA-4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / agonists
  • Adenosine Triphosphate / immunology
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • Ceramides / agonists
  • Ceramides / immunology
  • Ceramides / pharmacology
  • Chemokine CXCL12 / agonists
  • Chemokine CXCL12 / immunology
  • Chemokine CXCL12 / pharmacology
  • Chemotactic Factors / agonists
  • Chemotactic Factors / immunology
  • Chemotactic Factors / pharmacology*
  • Chemotaxis / drug effects
  • Dinoprostone / therapeutic use
  • Graft Survival / drug effects*
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / chemistry
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Lysophospholipids / agonists
  • Lysophospholipids / immunology
  • Lysophospholipids / pharmacology
  • Membrane Microdomains / drug effects
  • Receptors, CXCR4 / agonists
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / immunology
  • Sphingosine / agonists
  • Sphingosine / analogs & derivatives
  • Sphingosine / immunology
  • Sphingosine / pharmacology
  • Stem Cell Niche / drug effects*
  • Stem Cell Niche / immunology
  • Uridine Triphosphate / agonists
  • Uridine Triphosphate / immunology
  • Valproic Acid / therapeutic use

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Ceramides
  • Chemokine CXCL12
  • Chemotactic Factors
  • Lysophospholipids
  • Receptors, CXCR4
  • ceramide 1-phosphate
  • sphingosine 1-phosphate
  • Valproic Acid
  • Adenosine Triphosphate
  • Dinoprostone
  • Sphingosine
  • Uridine Triphosphate