Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

Xinxin Huang, Hal Broxmeyer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is a life-saving treatment for a variety of hematological and nonhematological disorders. Successful clinical outcomes after transplantation rely on adequate hematopoietic stem cell (HSC) numbers, and the homing and subsequent short-term and long-term engraftment of these cells in the bone marrow. Enhancing the homing capability of HSCs has the potential for high impact on improving HCT and patient survival. RECENT FINDINGS: There are a number of ways to enhance HSC engraftment. Neutralizing negative epigenetic regulation by histone deacetylase 5 (HDAC5) increases surface CXCR4 expression and promotes human HSC homing and engraftment in immune-deficient NSG (NOD.Cg-Prkdc IL2rgt/Sz) mice. Short-term treatment of cells with glucocorticoids, pharmacological stabilization of hypoxia-inducible factor (HIF)-1α, increasing membrane lipid raft aggregation, and inhibition of dipeptidyl peptidase 4 (DPP4) facilitates HSC homing and engraftment. Added to these procedures, modulating the mitochondria permeability transition pore (MPTP) to mitigate ambient air-induced extra physiological oxygen stress/shock (EPHOSS) by hypoxic harvest and processing, or using cyclosporine A during air collection increases functional HSC numbers and improves HSC engraftment. SUMMARY: A better understanding of the regulation of human HSC homing mediated by various signaling pathways will facilitate development of more efficient means to enhance HCT efficacy.

Original languageEnglish (US)
Pages (from-to)266-272
Number of pages7
JournalCurrent opinion in hematology
Volume26
Issue number4
DOIs
StatePublished - Jul 1 2019

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Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Cell Transplantation
Cell Count
Air
Dipeptidyl Peptidase 4
Hypoxia-Inducible Factor 1
Histone Deacetylases
Membrane Lipids
Epigenomics
Bone Marrow Cells
Cyclosporine
Glucocorticoids
Shock
Permeability
Mitochondria
Transplantation
Pharmacology
Oxygen
Survival

ASJC Scopus subject areas

  • Hematology

Cite this

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation. / Huang, Xinxin; Broxmeyer, Hal.

In: Current opinion in hematology, Vol. 26, No. 4, 01.07.2019, p. 266-272.

Research output: Contribution to journalArticle

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