干细胞显现性别差异 雌性组织再生更易

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干细胞显现性别差异 雌性组织再生更易 美国匹兹堡大学医学院近日研究发现，干细胞存在性别差异，从雌性小鼠肌肉中提取的干细胞比雄性肌肉中提取的更易分化为身体组织。这一发现将对许多疾病的干细胞疗法产生重要影响。科学家在长期研究中偶然发现，所使用的干细胞几乎全部来自雌性小鼠。他们随后对来自雄性和雌性的干细胞分别进行实验，发现两者确实存在差异。我们知道，胚胎干细胞可以分化为各种身体组织，而从成年动物中提取的肌肉干细胞则仅能分化为少数几种组织。研
干细胞存在性别差异，从雌性小鼠肌肉中提取的干细胞比雄性肌肉中提取的更易分化为身体组织。这一发现将对许多疾病的干细胞疗法产生重要影响。  

  科学家在长期研究中偶然发现，所使用的干细胞几乎全部来自雌性小鼠。他们随后对来自雄性和雌性的干细胞分别进行实验，发现两者确实存在差异。  

  我们知道，胚胎干细胞可以分化为各种身体组织，而从成年动物中提取的肌肉干细胞则仅能分化为少数几种组织。

  研究人员将从健康小鼠中提取的肌肉干细胞注射到患有基因疾病的小鼠体内，其中一些疾病类似人类的肌原性肌肉萎缩症等。  

  在注射了干细胞后，研究人员测量了干细胞再生肌肉纤维的能力，随后发现雌性干细胞比雄性干细胞能产生更多肌肉纤维。研究人员约翰尼-哈德表示：“不管患病的小鼠是雄性还是雌性，注射雌性干细胞总是有着更好的骨骼肌再生能力。”  

  研究者认为，这一差异的来源可能是雌性干细胞能更好应对免疫反应。当干细胞被注射后，有关的身体组织会发炎，肝细胞将面对许多自由基。这时，雄性干细胞的自我复制将会被阻碍。  

  不过研究人员仍不清楚造成这种差异的根本原因，但是他们相信在其它生物，包括人体内都存在这种差异。这一研究成果发表在4月9日出版的《细胞生物学期刊》上。


部分英文原文：

Published online 9 April 2007
doi:10.1083/jcb.200612094
The Journal of Cell Biology, Vol. 177, No. 1, 73-86


A role for cell sex in stem cell–mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency

Bridget M. Deasy1,2,3, Aiping Lu3, Jessica C. Tebbets3, Joseph M. Feduska3, Rebecca C. Schugar3, Jonathan B. Pollett2,3, Bin Sun3, Kenneth L. Urish1,3, Burhan M. Gharaibeh2,3, Baohong Cao2,3, Robert T. Rubin5, and Johnny Huard1,2,3,4

1 Department of Bioengineering, 2 Department of Orthopaedic Surgery, 3 Stem Cell Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, and 4 Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15260
5 Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles CA 90095

Correspondence to Johnny Huard: jhuard@pitt.edu

We have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic (mdx) mice efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneity in marker profiles and variability in regeneration abilities. We show here that cell sex is a variable that considerably influences MDSCs' regeneration abilities. We found that the female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently. Despite using additional isolation techniques and cell cloning, we could not obtain a male subfraction with a regeneration capacity similar to that of their female counterparts. Rather than being directly hormonal or caused by host immune response, this difference in MDSCs' regeneration potential may arise from innate sex-related differences in the cells' stress responses. In comparison with F-MDSCs, male MDSCs have increased differentiation after exposure to oxidative stress induced by hydrogen peroxide, which may lead to in vivo donor cell depletion, and a proliferative advantage for F-MDSCs that eventually increases muscle regeneration. These findings should persuade researchers to report cell sex, which is a largely unexplored variable, and consider the implications of relying on cells of one sex.

Abbreviations used in this paper: ANOVA, analysis of variance; F-MDSC, female MDSC; GM, growth medium; MDSC, muscle-derived stem cell; M-MDSC, male MDSC; MyHC, myosin heavy chain; PD, population doubling; PDT, PD time; RI, regeneration index; ROS, reactive oxygen species; SCID, severe combined immunodeficiency.

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