中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (19): 4882-4889.doi: 10.12307/2026.676

• 脐带脐血干细胞 umbilical cord blood stem cells • 上一篇    下一篇

人脐带间充质干细胞移植保护高原低氧诱导雄性小鼠的生殖损伤

崔  硕1，2，3，李秀娟1，2，4，王文婷1，2，4，杨丽红1，5，何  生1，6，雷立健3，解  军1，2，4   

  1. 1山西省出生缺陷与细胞再生重点实验室，山西省太原市  030001；2煤炭环境致病性与防治教育部重点实验室，山西省太原市  030001；山西医科大学，3公共卫生学院，4生物化学与分子生物学教研室，5病理教研室，山西省太原市  030001；6山西医科大学第一附属医院影像科，山西省临床细胞治疗转化试点基地，山西省太原市  030001
  • 收稿日期:2025-06-06 接受日期:2025-09-23 出版日期:2026-07-08 发布日期:2026-02-14
  • 通讯作者: 解军，博士，教授，山西省出生缺陷与细胞再生重点实验室，山西省太原市 030001；煤炭环境致病性与防治教育部重点实验室，山西省太原市 030001；山西医科大学生物化学与分子生物学教研室，山西省太原市 030001
  • 作者简介:崔硕，男，1998年生，山西省晋城市人，汉族，硕士，主要从事干细胞与组织再生研究。
  • 基金资助:
    中央引导地方科技发展基金项目(YDZJSX2021B008)，项目负责人：解军

Human umbilical cord mesenchymal stem cell transplantation protects against reproductive damage induced by high-altitude hypoxia exposure in male mice

Cui Shuo1, 2, 3, Li Xiujuan1, 2, 4, Wang Wenting1, 2, 4, Yang Lihong1, 5, He Sheng1, 6, Lei Lijian3, Xie Jun1, 2, 4   

  1. 1Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Taiyuan 030001, Shanxi Province, China; 2Key Laboratory of Coal Environment Pathogenicity and Prevention of Ministry of Education, Taiyuan 030001, Shanxi Province, China; 3School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 4Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 5Department of Pathology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 6Department of Radiology, The First Hospital of Shanxi Medical University, Shanxi Provincial Pilot Base for Clinical Cell Therapy Transformation, Taiyuan 030001, Shanxi Province, China
  • Received:2025-06-06 Accepted:2025-09-23 Online:2026-07-08 Published:2026-02-14
  • Contact: Xie Jun, MD, Professor, Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Taiyuan 030001, Shanxi Province, China; Key Laboratory of Coal Environment Pathogenicity and Prevention of Ministry of Education, Taiyuan 030001, Shanxi Province, China; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • About author:Cui Shuo, MS, Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Taiyuan 030001, Shanxi Province, China; Key Laboratory of Coal Environment Pathogenicity and Prevention of Ministry of Education, Taiyuan 030001, Shanxi Province, China; School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Supported by:
    Central Guidance Local Science and Technology Development Fund Project, No. YDZJSX2021B008 (to XJ)

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摘要：

文题释义：

人脐带间充质干细胞：是指存在于新生儿脐带组织中的一种多能干细胞，具有较强的增殖能力和高度分化潜力，在特定条件下可分化为多种功能细胞类型，在组织修复和再生中发挥重要作用。此外，人脐带间充质干细胞因来源明确、易于获取且无伦理争议，已成为研究发育生物学和再生医学的重要工具。
生殖损伤：是指生殖器官或生殖系统的功能障碍或结构性破坏，这种损伤可能导致生育能力下降甚至完全丧失，主要表现包括精子生成功能的异常(如精子数量减少、精液量减少)、性激素分泌紊乱等。

摘要
背景：高原低氧环境可损伤男性生殖系统，干细胞是否能够保护高原低氧环境引起的雄性生殖系统损伤仍未见报道。
目的：探讨人脐带间充质干细胞移植对低氧雄性小鼠生殖损伤的预防效应。
方法：分离培养人脐带间充质干细胞并进行三系分化及流式鉴定。21只C57BL/6雄性小鼠随机分为对照组、低氧组和干细胞组(n=7)。低氧组和干细胞组构建模拟海拔5 000 m大气含氧量(体积分数11.1%氧气)的小鼠慢性间歇低氧模型。干细胞组小鼠在低氧暴露每周的最后1 d，尾静脉注射1×106人脐带间充质干细胞，每周1次，共注射6次，其余组注射PBS。实验期间监测小鼠体质量、摄食量和饮水量。低氧暴露结束后，对睾丸组织进行形态学、超微结构、活性氧水平、线粒体膜电位分析；对附睾组织进行苏木精-伊红染色及精子活力分析；通过DIL荧光示踪法观察干细胞的归巢能力。
结果与结论：①人脐带间充质干细胞移植显著改善了低氧小鼠的饮水和摄食量，但对体质量无明显影响；②形态学分析显示，低氧引起小鼠睾丸和附睾水肿，生精细胞脱落，而人脐带间充质干细胞移植缓解了低氧造成的组织结构损伤，并逆转了生殖细胞线粒体肿胀和萎缩；同时，人脐带间充质干细胞移植显著抑制了低氧诱发的活性氧增高，恢复低氧小鼠的线粒体膜电位，并提高低氧小鼠的精子活力；③示踪实验显示：人脐带间充质干细胞进入小鼠体内后，主要聚集在肺组织，而在睾丸的归巢能力较低。总之，人脐带间充质干细胞移植可通过保护生殖细胞线粒体结构及功能，减轻低氧造成的睾丸及附睾水肿，从而恢复小鼠生精功能及精子活力。

关键词: 高原低氧, 脐带间充质干细胞, 睾丸, 超微结构, 活性氧, 线粒体, 精子活力, 示踪

Abstract: BACKGROUND: High-altitude hypoxia has been reported to damage the male reproductive system, but whether stem cells can protect against male reproductive damage caused by high-altitude hypoxia has not been reported.
OBJECTIVE: To investigate the preventive effect of human umbilical cord mesenchymal stem cell transplantation on reproductive damage in hypoxia-exposed male mice.
METHODS: Human umbilical cord mesenchymal stem cells were isolated and cultured to identify the three-lineage differentiation and specific phenotype markers. Totally 21 C57BL/6 male mice were randomly divided into control, hypoxia, and stem cell groups (n=7). A mouse model of chronic-intermittent hypoxia was established to simulate hypoxia exposure at an altitude of 5 000 m (11.1% oxygen volume fraction) in the hypoxia and stem cell groups. On the last day of each week of hypoxia exposure, mice in the stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for a total of 6 injections, while the other groups were injected with PBS. Mouse body weight, food and water intake were monitored during the experiment. After the end of hypoxia exposure, the testes were analyzed for morphology, ultrastructure, reactive oxygen species level and mitochondrial membrane potential. The epididymal tissues were analyzed for hematoxylin-eosin staining and sperm motility. The homing ability of the stem cells was observed by DIL tracer method.
RESULTS AND CONCLUSION: (1) Human umbilical cord mesenchymal stem cell transplantation significantly improved water and food intake in hypoxic mice, but had no significant effect on body weight. (2) Morphological analysis revealed that hypoxia induced edema in the testes and epididymides of mice, accompanied by the shedding of spermatogenic cells. In contrast, human umbilical cord mesenchymal stem cell transplantation alleviated the structural damage caused by hypoxia exposure and the swelling and atrophy of germ cell mitochondria. Additionally, human umbilical cord mesenchymal stem cell transplantation significantly reduced the reactive oxygen species levels induced by hypoxia exposure, restored the mitochondrial membrane potential, and enhanced sperm motility in hypoxic mice. (3) Tracer experiments indicated that human umbilical cord mesenchymal stem cells, after being injected into mice through the tail vein, mainly accumulated in the lung tissue and had a lower homing capacity in the testis. In conclusion, human umbilical cord mesenchymal stem cell transplantation effectively protected the mitochondrial structure and function of germ cells, alleviated testicular and epididymal edema caused by hypoxia, and thus restored spermatogenesis and sperm motility in mice.

Key words: high-altitude hypoxia, umbilical cord mesenchymal stem cell, testis, ultrastructure, reactive oxygen species, mitochondria, sperm motility, tracing

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