Differentiation of human umbilical cord mesenchymal stem cells into germ-like cells in mouse seminiferous tubules

Chen,Hui; Tang,Qiu‑Ling; Wu,Xiao‑Ying; Xie,Li‑Chun; Lin,Li‑Min; Ho,Gu‑Yu; Ma,Lian

doi:10.3892/mmr.2015.3528

Differentiation of human umbilical cord mesenchymal stem cells into germ-like cells in mouse seminiferous tubules

Authors:
- Hui Chen
- Qiu‑Ling Tang
- Xiao‑Ying Wu
- Li‑Chun Xie
- Li‑Min Lin
- Gu‑Yu Ho
- Lian Ma
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Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Pediatrics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Transformation Medical Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Pediatrics, Shenzhen Pingshan Maternal and Child Health Hospital, Shenzhen, Guangdong 518122, P.R. China
Published online on: March 23, 2015 https://doi.org/10.3892/mmr.2015.3528
Pages: 819-828
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Our previous study demonstrated that human umbilical cord mesenchymal stem cells (HUMSCs) were capable of differentiation into germ cells in vitro. To assess this potential in vivo, HUMSCs were microinjected into the lumen of seminiferous tubules of immunocompetent mice, which were treated with busulfan to destroy endogenous spermatogenesis. Bromodeoxyuridine labeling studies demonstrated that HUMSCs survived in the tubule for at least 120 days, exhibited a round cell shape typical of proliferating or differentiating germ cells, migrated to the basement of the tubule, where proliferating spermatogonia reside and returned to the luminal compartment, where differentiating spermatids and spermatozoa reside. The migration pattern resembled that of germ cell development in vivo. Immunohistochemical and colocalization studies revealed that transplanted HUMSCs expressed the germ cell markers octamer‑binding transcription factor 4, α6 integrin, C‑kit and VASA, confirming the germ cell differentiation. In addition, it was observed that tubules transplanted with HUMSCs exhibited marked improvement in the histological features damaged by the chemotherapeutic busulfan, as judged by morphology and quantitative histology. Taken together, these data demonstrated the capacity of HUMSCs to form germ cells in the testes and to repair testicular tissue. These findings suggest a potential utility of HUMSCs to treat the infertility and testicular insufficiency caused by cancer therapeutics.

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