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Aldehyde Dehydrogenase Activity Identifies a Population of Human Skeletal Muscle Cells With High Myogenic Capacities

机译:醛脱氢酶活性确定具有高成肌能力的人骨骼肌细胞群体

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摘要

Aldehyde dehydrogenase 1A1 (ALDH) activity is one hallmark of human bone marrow (BM), umbilical cord blood (UCB), and peripheral blood (PB) primitive progenitors presenting high reconstitution capacities in vivo. In this study, we have identified ALDH+ cells within human skeletal muscles, and have analyzed their phenotypical and functional characteristics. Immunohistofluorescence analysis of human muscle tissue sections revealed rare endomysial cells. Flow cytometry analysis using the fluorescent substrate of ALDH, Aldefluor, identified brightly stained (ALDHbr) cells with low side scatter (SSClo), in enzymatically dissociated muscle biopsies, thereafter abbreviated as SMALD+ (for skeletal muscle ALDH+) cells. Phenotypical analysis discriminated two sub-populations according to CD34 expression: SMALD+/CD34− and SMALD+/CD34+ cells. These sub-populations did not initially express endothelial (CD31), hematopoietic (CD45), and myogenic (CD56) markers. Upon sorting, however, whereas SMALD+/CD34+ cells developed in vitro as a heterogeneous population of CD56− cells able to differentiate in adipoblasts, the SMALD+/CD34− fraction developed in vitro as a highly enriched population of CD56+ myoblasts able to form myotubes. Moreover, only the SMALD+/CD34− population maintained a strong myogenic potential in vivo upon intramuscular transplantation. Our results suggest that ALDH activity is a novel marker for a population of new human skeletal muscle progenitors presenting a potential for cell biology and cell therapy.
机译:醛脱氢酶1A1(ALDH)活性是在体内具有高重构能力的人骨髓(BM),脐带血(UCB)和外周血(PB)原始祖细胞的标志之一。在这项研究中,我们已经确定了人类骨骼肌中的ALDH +细胞,并分析了它们的表型和功能特征。对人体肌肉组织切片的免疫组织荧光分析显示罕见的肌内膜细胞。使用ALDH的荧光底物Aldefluor进行的流式细胞仪分析在酶解的肌肉活检中鉴定出具有低侧向散射(SSClo)的亮染(ALDHbr)细胞,此后缩写为SMALD +(对于骨骼肌ALDH +)。表型分析根据CD34表达区分了两个亚群:SMALD + / CD34-和SMALD + / CD34 +细胞。这些亚群最初不表达内皮(CD31),造血(CD45)和成肌(CD56)标记。然而,分选后,SMALD + / CD34 +细胞在体外发展成为能够在成脂细胞中分化的异质CD56-细胞群体,而SMALD + / CD34-组分在体外发展为能够形成肌管的高浓缩CD56 +成肌细胞群体。此外,在肌肉内移植后,只有SMALD + / CD34-群体在体内具有很强的成肌潜力。我们的结果表明,ALDH活性是新的人类骨骼肌祖细胞群体的一种新型标志物,具有细胞生物学和细胞治疗的潜力。

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