![]() ![]() D,E, Representative dot plots and percentages of donor LSK cells (CD45.1 +CD45.2 −LSK) in the 2° recipient BMs at 20 weeks after 2° transplantation. C, The percentages of donor CD45.1 + cells in the 2° recipient BMs at 20 weeks after transplantation. B, Flow cytometric analyses of the donor CD45.1 + cell percentages in the PB at 4, 8, and 12 weeks after 2° transplantation (mean ± SD, n = 8 for the control group and n = 10 for the TPO treatment group). Lethally irradiated CD45.2 + mice (1° recipients) received CD45.1 + BM MNCs and single doses of TPO or PBS treatment (mean ± SD, n = 8 for the control group and n = 10 for the TPO treatment group). A, Schematic representation of the homed CD45.1 + BM cell engraftment assays from the competitive and noncompetitive transplantation experiments. ![]() TPO enhances engraftment of HSPCs to the BM. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. The clinical trial was registered in the Chinese Clinical Trial Registry website (as ChiCTR-OIN-1701083.Įngraftment hematopoietic stem and progenitor cells homing matrix metalloproteinase 9 thrombopoietin. Thus, our data provide a simple, feasible, and efficient approach to improve clinical outcomes in patients with allogenic hematopoietic stem cell transplantation. The mean volume of platelet and red blood cell transfusion was remarkably reduced in the cohort of patients with SAA or hematological malignancies receiving TPO treatment. Surprisingly, single doses of TPO treatment to patients followed by hematopoietic stem cell transplantation significantly improved platelet engraftment in the cohort of patients with severe aplastic anemia (SAA). We then performed a clinical trial to evaluate the effect of TPO treatment in patients receiving haploidentical BM and mobilized peripheral blood transplantation. More importantly, a single dose of TPO remarkably promoted human HSPC homing and subsequent engraftment to the BM of nonobese diabetic/severe combined immunodeficiency mice. Blocking the interaction of SDF-1α and CXCR4 on HSPCs by using AMD3100 could significantly reverse the TPO-enhanced HSPC homing effect. As a result, SDF-1α level was increased in the BM niche. We found that TPO could downregulate the expression and secretion of matrix metalloproteinase 9 in BM cells. Single doses of TPO treatment to the recipients immediately after BM transplantation showed significantly improved homing of HSPCs to the BM, which subsequently resulted in enhanced short- and long-term engraftment of HSPCs in mice. We reported a novel function of recombinant human thrombopoietin (TPO) in increasing hematopoietic stem and progenitor cell (HSPC) homing to the bone marrow (BM). ![]()
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