Open Access

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

  • Authors:
    • Da‑Won Choi
    • Kyung‑Ah Cho
    • Hyun‑Ji Lee
    • Yu‑Hee Kim
    • Kyong‑Je Woo
    • Joo‑Won Park
    • Kyung‑Ha Ryu
    • So‑Youn Woo
  • View Affiliations

  • Published online on: June 24, 2020     https://doi.org/10.3892/ijmm.2020.4657
  • Pages: 1166-1174
  • Copyright: © Choi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 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.

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September-2020
Volume 46 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Choi DW, Cho KA, Lee HJ, Kim YH, Woo KJ, Park JW, Ryu KH and Woo SY: Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning. Int J Mol Med 46: 1166-1174, 2020
APA
Choi, D., Cho, K., Lee, H., Kim, Y., Woo, K., Park, J. ... Woo, S. (2020). Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning. International Journal of Molecular Medicine, 46, 1166-1174. https://doi.org/10.3892/ijmm.2020.4657
MLA
Choi, D., Cho, K., Lee, H., Kim, Y., Woo, K., Park, J., Ryu, K., Woo, S."Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning". International Journal of Molecular Medicine 46.3 (2020): 1166-1174.
Chicago
Choi, D., Cho, K., Lee, H., Kim, Y., Woo, K., Park, J., Ryu, K., Woo, S."Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning". International Journal of Molecular Medicine 46, no. 3 (2020): 1166-1174. https://doi.org/10.3892/ijmm.2020.4657