The use of chemokine receptor agonists in stem cell mobilization

Abstract

Introduction: Pharmacological mobilization has been exploited as a means to obtain hematopoietic stem progenitor cells (HSPCs) for hematopoietic reconstitution. HSPCs mobilized from bone marrow into peripheral blood (PB) are a preferred source of stem cells for transplantation, because they are easily accessible and evidence indicates that they engraft faster after transplantation than HSPCs directly harvested from bone marrow (BM) or umbilical cord blood (UCB).

Areas covered: Since chemokine–chemokine receptor axes are involved in retention of HSPCs in the BM microenvironment, chemokine receptor agonists have been proposed as therapeutics to facilitate the mobilization process. These compounds include agonists of the CXCR4 receptor expressed on HSPCs (CTCE-0021 and ATI-2341) or chemokines binding to chemokine receptors expressed on granuclocytes and monocytes (e.g., CXCL2, also known as the growth-related oncogene protein-beta (Gro-β); CCL3, also known as macrophage inflammatory protein-1α (MIP-1α); or CXCL8, also known as IL-8) could be employed alone or in combination with other mobilizing agents (e.g., G-CSF or Plerixafor (AMD3100)). We discuss the current state of knowledge about chemokine receptor agonists and the rationale for their application in mobilization protocols.

Expert opinion: Evidence is accumulating that CXCR4 receptor agonists could be employed alone or with other agents as mobilizing drugs. In particular they may provide an alternative for patients that are poor mobilizers.

Keywords:

• CXCL12 (SDF-1)
• CXCL2 (Gro-beta)
• CXCR4
• pepducins

Notes

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