Co-transplantation of tonsil-derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning

Da Won Choi, Kyung Ah Cho, Hyun Ji Lee, Yu Hee Kim, Kyong Je Woo, Joo Won Park, Kyung Ha Ryu, So Youn Woo

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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 CD 3+ 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.

Original languageEnglish
Pages (from-to)1166-1174
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume46
Issue number3
DOIs
StatePublished - Sep 2020

Keywords

  • Bone marrow transplantation
  • T cell diversity
  • Thymus
  • Tonsil-derived mesenchymal stromal cells

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