Back to Search
Start Over
Thrombopoietin enhances hematopoietic stem and progenitor cell homing by impeding matrix metalloproteinase 9 expression
- Source :
- Stem Cells Translational Medicine, Stem Cells Translational Medicine, Vol 9, Iss 6, Pp 661-673 (2020)
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- We reported a novel function of recombinant human thrombopoietin (TPO) in increasing hematopoietic stem and progenitor cell (HSPC) homing to the bone marrow (BM). 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 found that TPO could downregulate the expression and secretion of matrix metalloproteinase 9 in BM cells. As a result, SDF‐1α level was increased in the BM niche. Blocking the interaction of SDF‐1α and CXCR4 on HSPCs by using AMD3100 could significantly reverse the TPO‐enhanced HSPC homing effect. 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. We then performed a clinical trial to evaluate the effect of TPO treatment in patients receiving haploidentical BM and mobilized peripheral blood transplantation. 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). 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. Thus, our data provide a simple, feasible, and efficient approach to improve clinical outcomes in patients with allogenic hematopoietic stem cell transplantation. The clinical trial was registered in the Chinese Clinical Trial Registry website (http://www.chictr.org.cn) as ChiCTR‐OIN‐1701083.<br />We reported a novel function of recombinant human thrombopoietin (TPO) in increasing hematopoietic stem and progenitor cell (HSPC) homing to the bone marrow (BM), which subsequently resulted in enhanced long‐term engraftment of HSPCs in mice. Notably, single doses of TPO treatment to patients followed by HSCT improved clinical outcomes, especially in patients with severe aplastic anemia.
- Subjects :
- Male
0301 basic medicine
medicine.medical_treatment
hematopoietic stem and progenitor cells
Hematopoietic stem cell transplantation
CXCR4
Mice
0302 clinical medicine
Human Clinical Article
thrombopoietin
Child
lcsh:R5-920
lcsh:Cytology
Hematopoietic Stem Cell Transplantation
General Medicine
Recombinant Proteins
Tissue Donors
Haematopoiesis
Treatment Outcome
medicine.anatomical_structure
Matrix Metalloproteinase 9
Female
homing
lcsh:Medicine (General)
Erythrocyte Transfusion
engraftment
Adult
Adolescent
Platelet Engraftment
Down-Regulation
Bone Marrow Cells
Young Adult
03 medical and health sciences
medicine
Animals
Humans
lcsh:QH573-671
Progenitor cell
business.industry
Cell Biology
Hematopoietic Stem Cells
Mice, Inbred C57BL
Transplantation
030104 developmental biology
Cancer research
Bone marrow
business
030217 neurology & neurosurgery
Developmental Biology
Homing (hematopoietic)
Subjects
Details
- ISSN :
- 21576580 and 21576564
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Stem Cells Translational Medicine
- Accession number :
- edsair.doi.dedup.....7e4819c438c01f05ccf5a73311711228