Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (19): 2953-2959.doi: 10.12307/2023.643

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Effects of bone marrow mesenchymal stem cells on the structure and function of thymus and spleen in aging rhesus monkeys

Pan Hang1, 2, Zhu Xiangqing2, He jie2, Yang Zailing4, Tian Chuan2, Lyu Guanke5, Ruan Guangping2, Ye Li1, 2, He Zhixu6, Shu Liping3, Pan Xinghua2   

  1. 1Tissue Engineering and Stem Cell Experimental Center, Guizhou Medical University, Guiyang 550004, Guizhou Province, China; 2Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Basic Medical Laboratory, 920 Hospital of Joint Logistics Support Force of Chinese PLA, Kunming 650032, Yunnan Province, China;3Department of Immunology of School of Basic Medicine of Guizhou Medical University, National and Local Joint Engineering Laboratory of Cell Engineering Biomedical Technology, Key Laboratory of Regenerative Medicine of Guizhou Province, State Key Laboratory of Efficacy and Utilization of Medicinal Plants Co-constructed by Province and Ministry, Key Laboratory of Translational Research of Adult Stem Cell of Chinese Academy of Medical Sciences, Guiyang 550004, Guizhou Province, China; 4Tumor Hospital, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China; 5Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu 610000, Sichuan Province, China; 6Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi 563100, Guizhou Province, China
  • Received:2022-07-13 Accepted:2022-08-25 Online:2023-07-08 Published:2022-11-28
  • Contact: Pan Hang, Master candidate, Tissue Engineering and Stem Cell Experimental Center, Guizhou Medical University, Guiyang 550004, Guizhou Province, China; Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Basic Medical Laboratory, 920 Hospital of Joint Logistics Support Force of Chinese PLA, Kunming 650032, Yunnan Province, China
  • About author:Pan Xinghua, MD, Chief physician, Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Basic Medical Laboratory, 920 Hospital of Joint Logistics Support Force of Chinese PLA, Kunming 650032, Yunnan Province, China Shu Liping, MD, Professor, Department of Immunology of School of Basic Medicine of Guizhou Medical University, National and Local Joint Engineering Laboratory of Cell Engineering Biomedical Technology, Key Laboratory of Regenerative Medicine of Guizhou Province, State Key Laboratory of Efficacy and Utilization of Medicinal Plants Co-constructed by Province and Ministry, Key Laboratory of Translational Research of Adult Stem Cell of Chinese Academy of Medical Sciences, Guiyang 550004, Guizhou Province, China
  • Supported by:
    the Major Science and Technology Project of Yunnan Science and Technology Plan Project, No. 2018ZF007 (to PXH)

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Abstract: BACKGROUND: With the increase of age, the structure and function of the spleen changed, and the thymus gradually atrophied and degenerated after puberty, resulting in immune dysfunction.  
OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells on the structure and function of thymus and spleen in aging rhesus monkeys.
METHODS: Six aging rhesus monkeys with an average age of 25 years were randomly divided into elderly group (n=3) and elderly treatment group (n=3). Rhesus monkeys in the elderly treatment group were infused with the 4th generation bone marrow mesenchymal stem cells (1×107/kg) labeled with superparamagnetic iron nanoparticles through femoral vein once a day for 3 consecutive days. Rhesus monkeys in the elderly group were infused with the same volume of normal saline at the same time. The rhesus monkeys were euthanized 5 months after the last infusion of bone marrow mesenchymal stem cells. The thymus and spleen tissues were obtained. The structural changes of thymus and spleen tissues were observed by hematoxylin and eosin staining. Immunofluorescence staining was used to analyze the expression of T cell subsets and age-related gene protein P21 in thymus tissues. Immunohistochemical staining was used to analyze the expression of T cell subsets and age-related gene protein P21 in spleen tissues. Before euthanized, 5 mL of femoral venous blood was extracted by heparin tube. The levels of tumor necrosis factor-α and interleukin-1α in peripheral blood serum were analyzed by enzyme-linked immunosorbent assay.  
RESULTS AND CONCLUSION: (1) Superparamagnetic iron nanoparticles labeled bone marrow mesenchymal stem cells could colonize and play a role in aging thymus and spleen tissues in rhesus monkeys. (2) After transplantation of bone marrow mesenchymal stem cells, the cortex and medulla junction appeared in some tissues of the aged rhesus monkeys, and the adipocytes decreased, and the thymic body appeared, and the structure of thymus changed to normal. The splenic tissue of aged rhesus monkeys showed a clear boundary between red pulp and white pulp, and the edge of the splenic body was more complete, and the macrophages were reduced, and the structure of spleen tissue changed to normal. (3) Compared with the elderly group, the expression of CD3+, CD4+ and CD8+ T cells in senile thymus and spleen tissues in the elderly treatment group showed a trend of increase. The expression of P21 protein in senile thymus and spleen tissues in the elderly treatment group showed a significant downward trend. (4) Compared with the elderly group, the levels of tumor necrosis factor-α and interleukin-1α in peripheral blood of the elderly treatment group showed a significant downward trend. (5) These results indicated that transplantation of bone marrow mesenchymal stem cells could improve the structure and function of thymus and spleen tissues in aged rhesus monkeys.

Key words: stem cell, bone marrow mesenchymal stem cell, rhesus monkey, thymus, spleen, anti-aging, immunity, senescence-associated secretory phenotype

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