Co transplantation of tonsil derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning
Bone marrow (BM) transplantation (BMT) represents a curative treatment for various hematological disorders. Prior to BMT, a large amount of the relevant anticancer drug needed to be administered to eliminate cancer cells. However, during this pre BMT cytotoxic conditioning regimen, hematopoietic stem cells in the BM and thymic epithelial cells were also destroyed. The T cell receptor (TCR) recognizes diverse pathogen, tumor and environmental antigens, and confers immunological memory and self tolerance. Delayed thymus reconstitution following pre BMT cytotoxic conditioning impedes de novo thymopoiesis and limits T cell mediated immunity. Several cytokines, such as RANK ligand, interleukin (IL) 7, IL 22 and stem cell factor, were recently reported to improve thymopoiesis and immune function following BMT. In the present study, it was found that the co transplantation of tonsil derived mesenchymal stromal cells (T MSCs) with BM derived cells (BMCs) accelerated the recovery of involuted thymuses in mice following partial pre BMT conditioning with busulfan cyclophosphamide treatment, possibly by inducing FMS like tyrosine kinase 3 ligand (FLT3L) and fibroblast growth factor 7 (FGF7) production in T MSCs. The co transplantation of T MSCs with BMCs also replenished the CD3+ cell population by inhibiting thymocyte apoptosis following pre BMT cytotoxic conditioning. Furthermore, T MSC co transplantation improved the recovery of the TCR repertoire and led to increased thymus generated T cell diversity.
International journal of molecular medicine