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Human bone marrow mesenchymal stem cells expressing SDF-1 promote hematopoietic stem cell function of human mobilised peripheral blood CD34+ cells in vivo and in vitro
Abstract:Purpose:?There is mounting evidence demonstrating that stromal cell derived factor-1 (SDF-1) plays an important role in homing of hematopoietic progenitor cells to bone marrow. This study was aimed to assess whether bone marrow mesenchymal stem cells overexpressing exogenous SDF-1 could synergistically promote the homing of CD34+ (Cluster of Differentiation [CD]) cells to bone marrow of lethally irradiated severe combined immunodeficiency (SCID) mice.

Methods:?Human SDF-1 complementary Deoxyribonucleic acid (cDNA) was transfected into bone marrow-derived mesenchymal stem cells with recombinant lentiviral vector. The expression of SDF-1 was detected by real-time Polymerase Chain Reaction (PCR) and Enzyme-Linked Immunosorbent Assay (ELISA), and the ex vivo chemotaxis function on CD34+ cells was measured by coculture system and Transwell system. SDF-1 gene-modified mesenchymal stem cell (MSC) and CD34+ cells were infused into lethally irradiated SCID mice and the hematopoietic reconstitution in the recipient mice was examined.

Results:?Messenger ribonucleic acid (mRNA) and protein of SDF-1 in infected MSC were significantly higher than that of the non-infected control MSC (p?+ cells in?vitro and promote hematopoietic reconstitution after CD34+ cell transplantation in?vivo.

Conclusion:?MSC with high-level expression of SDF-1 can synergistically promote hematopoietic reconstitution after CD34+ cell transplantation in lethally irradiated SCID mice.
Keywords:bone marrow transplantation  gene therapy  radiation  stem cells  SCID
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