Cotransplantation of tonsilderived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning.
Int J Mol Med
; 46(3): 1166-1174, 2020 Sep.
Article
in En
| MEDLINE
| ID: mdl-32582998
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 preBMT 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 selftolerance. Delayed thymus reconstitution following preBMT cytotoxic conditioning impedes de novo thymopoiesis and limits T cellmediated immunity. Several cytokines, such as RANK ligand, interleukin (IL)7, IL22 and stem cell factor, were recently reported to improve thymopoiesis and immune function following BMT. In the present study, it was found that the cotransplantation of tonsilderived mesenchymal stromal cells (TMSCs) with BMderived cells (BMCs) accelerated the recovery of involuted thymuses in mice following partial preBMT conditioning with busulfancyclophosphamide treatment, possibly by inducing FMSlike tyrosine kinase 3 ligand (FLT3L) and fibroblast growth factor 7 (FGF7) production in TMSCs. The cotransplantation of TMSCs with BMCs also replenished the CD3+ cell population by inhibiting thymocyte apoptosis following preBMT cytotoxic conditioning. Furthermore, TMSC cotransplantation improved the recovery of the TCR repertoire and led to increased thymusgenerated T cell diversity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymus Gland
/
Palatine Tonsil
/
T-Lymphocytes
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Bone Marrow Transplantation
/
Mesenchymal Stem Cells
Limits:
Animals
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2020
Document type:
Article