Objective: To investigate the dynamic distribution of human bone marrow mesenchymal stem cells (hBM-MSCs) in mdx mice.
Methods: Twenty-four 8-10-week-old immunocompromised mdx mice were transplanted with 1 x 10(7) passage 5 hBM-MSCs labeled with bromodeoxyuridine (BrdU) by means of injection into the tail vein. The mice were euthanized 48 hours and 2, 4, 8, 12, 16, 20, and 24 weeks after transplantation. BrdU-positive cells in tissue and organs of the mice were detected by immunofluorescence analysis. Skeletal muscle was stained for anti-human nuclei mouse monoclonal antibody (anti-Hu) and analyzed for human dystrophin (Dys) expression by immunohistochemistry and reverse transcription-polymerase chain reaction.
Results: After transplantation, BrdU-positive cells were found in most organs (especially in bone marrow, liver, and lung) within 4 weeks, and these cells in liver and lung decreased gradually after 4 weeks. At 48 hours after transplantation, BrdU-positive cells were found in bone marrow, which reached a peak level after 2 weeks and were still detectable after 16 weeks. BrdU-positive cells in skeletal muscle increased gradually over time of transplantation. A small number of anti-Hu positive cells were detected in skeletal muscle 2 weeks after transplantation. A small number of Dys positive cell were seldom found at 4 weeks and small Dys mRNA expression detected 4 weeks after transplantation. The proportion of anti-Hu in parallel with Dys positive cells and Dys mRNA in skeletal muscle of mdx mice increased gradually over time of transplantation.
Conclusion: After being transplanted into mdx mice, hBM-MSCs are mainly distributed in bone marrow, liver, and lung during the early time (2-4 weeks) , and then in bone marrow and skeletal muscle (after 4 weeks).
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