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2007-4-24 9:15:21

JCB:研究显示女性肌肉干细胞再生能力较卓越

    根据英国匹兹堡大学医学中心(University  of  Pittsburgh  Medical  Center;UPMC)儿童医院的研究者最新研究显示,由女性肌肉中所分离出的干细胞再生能力优于男性。这项结果于4月9日发表在Journal  of  Cell  Biology期刊中,是首次着眼于性别差异的干细胞再生相关研究。  

   「这项发现对于以干细胞为基础的各项相关疗法会带来不小的影响。」干细胞研究中心主任Johnny  Huard博士表示,「未来以干细胞来发展组织再生药物的相关应用时,应当视性别为一个重要的决定因素。」  

    研究者在找寻研究杜馨氏肌肉失养症(Duchene  muscular  dystrophy,DMD)等肌肉萎缩遗传疾病疗法时发现,分离的雌性个体干细胞具有优良的再生新骨骼肌组织的能力。在给予患有DMD的实验鼠分别注射雌性与雄性干细胞之后,他们发现仅10%的注射雄性干细胞老鼠其再生系数(regeneration  index,RI)超过200者,而注射雌性干细胞者则高达40%。  

    「我们推测是雌性与雄性细胞对于周围的氧化压力承受能力不同;」匹兹堡大学医学中心整形外科与生物工程学专家Deasy博士指出。对于许多无法再生的组织伤害,干细胞是唯一的希望;这项研究无疑的]使干细胞疗法发展更往前跨展一步。


原始出处:

The Journal of Cell Biology, Vol. 177, No. 1, 73-86

Article

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

Abstract

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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