Xinxin Huang1, Hal E Broxmeyer. 1. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
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.
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.
Authors: Maegan L Capitano; Safa F Mohamad; Scott Cooper; Bin Guo; Xinxin Huang; Andrea M Gunawan; Carol Sampson; James Ropa; Edward F Srour; Christie M Orschell; Hal E Broxmeyer Journal: J Clin Invest Date: 2021-01-04 Impact factor: 14.808
Authors: Hal E Broxmeyer; Yan Liu; Reuben Kapur; Christie M Orschell; Arafat Aljoufi; James P Ropa; Thao Trinh; Sarah Burns; Maegan L Capitano Journal: Stem Cell Rev Rep Date: 2020-11-03 Impact factor: 5.739
Authors: James Ropa; Scott Cooper; Maegan L Capitano; Wouter Van't Hof; Hal E Broxmeyer Journal: Stem Cell Rev Rep Date: 2020-10-21 Impact factor: 6.692