Promoting Effects of Serotonin on Hematopoiesis: Ex Vivo Expansion of Cord Blood CD34⁺ Stem/Progenitor Cells, Proliferation of Bone Marrow Stromal Cells and Anti-Apoptosis

¹ Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Department of Paediatrics, The Chinese University of Hong Kong
² Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong
³ Department of Hematology, First Affiliated Hospital, Shantou University Medical College, Shantou, PR China
⁴ Laboratory Animal Services Centre, The Chinese University of Hong Kong, Hong Kong

^* To whom correspondence should be addressed. E-mail: lipang{at}cuhk.edu.hk.

	Abstract

Serotonin is a monoamine neurotransmitter that has multiple extraneuronal functions. We previously reported that serotonin exerted mitogenic stimulation on megakaryocytopoiesis mediated by 5-HT₂ receptors. In this study, we investigated effects of serotonin on ex vivo expansion of human cord blood CD34⁺ cells, bone marrow (BM) stromal cell colony-forming unit-fibroblast (CFU-F) formation and anti-apoptosis of megakaryoblastic M-07e cells. Our result showed that serotonin at 200 nM significantly enhanced the expansion of CD34⁺ cells to early stem/progenitors (CD34⁺ cells, CFU-GEMM) and multi-lineage committed progenitors (BFU/CFU-E, CFU-GM, CFU-MK, CD61⁺CD41⁺ cells). Serotonin also increased NOD/SCID-repopulating cells in the expansion culture, in terms of human CD45⁺, CD33⁺, CD14⁺ cells, BFU/CFU-E and CFU-GEMM engraftment in BM of animals 6 week post-transplantation. Serotonin alone or in addition to FGF, PDGF or VEGF, stimulated BM CFU-F formation. In M-07e cells, serotonin exerted anti-apoptotic effects (annexin V, caspase-3 and propidium iodide staining), and reduced mitochondria membrane potential (m) damage. The addition of ketanserin, a competitive antagonist of 5HT₂ receptor, nullified the anti-apoptotic effects of serotonin. Our data suggest the involvement of serotonin in promoting hematopoietic stem cells and the BM microenvironment. Serotonin could be developed for clinical ex vivo expansion of hematopoietic stem cells for transplantation.