The Reparative Effects of Human Adipose-Derived Mesenchymal Stem Cells in the Chemotherapy-Damaged Thymus

Stem Cells Dev. 2019 Feb 1;28(3):186-195. doi: 10.1089/scd.2018.0142. Epub 2019 Jan 10.

Abstract

Hematological patients who accept chemotherapy always develop secondary tumor or even die of severe infections. As an important central lymphoid organ, the thymus is frequently damaged during chemotherapy. Previous studies showed that the mesenchymal stem cells (MSCs) can promote the proliferation and repair of epithelial cells in thymus. The purpose of our study is to investigate the reparative effects of human adipose-derived mesenchymal stem cells (hADMSCs) in chemotherapy-treated damaged thymus. Eighty mice were randomly divided into four groups: normal group, model control group, hADMSCs untreated group, and hADMSCs treated group. The mice were injected intraperitoneally with dexamethasone sodium phosphate (Dex 20 mg/kg), except the normal group. Then, the chemotherapy models were obtained after 1 week; the treated group was infused intraperitoneally with hADMSCs, whereas the model control group was injected with equal volumes of normal saline. The hADMSC's infusion day was regarded as day 0. The mice were sacrificed at different time points (days 3, 7, 10, and 14). The pathological structure and the function of the thymus, the recovery of T-lymphocyte subpopulation, and the proportion of regulatory T (Treg) cells in spleen and peripheral blood were detected. Additionally, we transfected hADMSCs by lentivirus with green fluorescent protein (GFP) to confirm whether they home to thymus and detected the expressions of cytokines that are associated with the development of thymus in hADMSCs and thymus. The results of the study showed that the hADMSCs treated group had a more rapid recovery in terms of thymic pathological structure and function. The hADMSCs could home to the damaged thymus and secrete cytokines that played important roles in repairing damaged thymus. The results indicated that hADMSCs could repair the damaged thymus caused by chemotherapy and improve the immune microenvironment, which may be a potential treatment for hematological patients.

Keywords: T cell receptor excision circle (TREC); chemotherapy-damaged thymus; human adipose-derived mesenchymal stem cells (hADMSCs); keratinocyte growth factor (KGF).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Antineoplastic Agents, Hormonal / toxicity
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / toxicity
  • Humans
  • Lymphatic Diseases / chemically induced
  • Lymphatic Diseases / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Inbred C57BL
  • Regeneration*
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Thymus Gland / pathology
  • Thymus Gland / physiology*

Substances

  • Antineoplastic Agents, Hormonal
  • Cytokines
  • Dexamethasone