Effect of Allogenic Bone Marrow Mesenchymal Stem Cell Transplantation on T Cells of Old Mice

Abstract

To evaluate age-related changes in T cells and stem cell-related genes in mice and the changes in T cells and stem cell-related genes after allogenic bone marrow mesenchymal stem cell (BMSC) transplantation, BALB/c mice were divided into young (2 months, n = 5) and old (20 months, n = 5) groups and 1 × 10⁷ BMSCs from 3-week-old C57BL/6J mice were injected into the old mice (n = 5). T lymphocytes including CD3⁺, CD8⁺, CD8⁺CD28⁺, and CD8⁺CD44^lowCD62L^highSca-1⁺ stem cell-like memory T cells from spleens were analyzed by flow cytometry. mRNA transcriptions of the tumor suppressor p16^INK4A and the senescence inhibiting AUF 1 and stem cell-related ADAM12, GIL3, c-MYC, NANOG, Wnt, HOX11, Sox2, Oct3/4, and KLF4 genes were analyzed by quantitative reverse transcription–polymerase chain reaction for comparison between young and old mice and old mice after BMSC application. Stem cell-related genes were reduced transcribed in old mice, an action that could be partly or completely reversed for some genes by BMSC injections. The proportion of CD8⁺CD28⁺ T cells in the spleens of old mice was significantly reduced (p < 0.01), indicating advanced proliferative T cell senescence. The CD8⁺CD44^lowCD62L^high cell fraction was significantly reduced and that of CD8⁺CD44^lowCD62L^highSca-1⁺ increased in splenic CD8⁺ cells of old mice, both actions of which were reversed by BMSC injections. p16^INK4A transcription was enhanced and AUF1 transcription was reduced in old mice, the latter effect partly reversed by BMSC injections. BMSC injections led to recovery of stem cell-related gene activation or BMSC stem cell-related gene expression tolerance in spleens of old mice.