Journal
CURRENT OPINION IN HEMATOLOGY
Volume 25, Issue 4, Pages 245-252Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0000000000000429
Keywords
expansion; homing; human hematopoietic stem cell; nuclear receptor
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Funding
- US Public Health Service from the NIH [R01 HL112669, R01 HL056416, U54 DK106846]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL112669, R01HL056416] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U54DK106846] Funding Source: NIH RePORTER
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Purpose of review Allogeneic hematopoietic cell transplantation (HCT) is a life-saving therapy for hematological and nonhematological diseases. Cord blood is a source of transplantable hematopoietic stem cells (HSCs), but limited numbers of HSCs in single cord blood units, which may cause delayed neutrophil, platelet, and immune cell reconstitution, is a major problem for efficient transplantation. Ex-vivo expansion and enhanced homing of cord blood HSC may overcome this disadvantage and improve its long-term engraftment. Here, we discuss the role of nuclear hormone receptors signaling in human cord blood HSC engraftment. Recent findings Antagonizing retinoid acid receptor (RAR) signaling promotes human HSC expansion and increases myeloid cell production. Cord blood CD34(+) cells expanded by SR1 promotes efficient myeloid recovery after transplantation compared with control groups, and leads to successful engraftment. Short-term treatment of glucocorticoids enhances homing and long-term engraftment of human HSCs and HPCs in NSG mice. Peroxisome proliferator-activated receptor-g (PPAR gamma) antagonism expands human HSCs and HPCs by preventing differentiation and enhancing glucose metabolism. These findings demonstrate that nuclear hormone receptor signaling components might be promising targets for improving human cord blood HCT. Summary Better understanding of molecular mechanisms underlying human HSC expansion and homing mediated by nuclear hormone receptor signaling pathways will facilitate enhanced HCT efficacy.
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