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将人肌母细胞异种移植到免疫缺陷小鼠肌肉中后的存活建模。

Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle.

机构信息

BOA, INRA, Université de Tours, F-37380 Nouzilly, France.

Sorbonne Université, INSERM, CNRS, Center for Research in Myology, Institute of Myology, F-75013, Paris, France.

出版信息

Exp Cell Res. 2018 Mar 15;364(2):217-223. doi: 10.1016/j.yexcr.2018.02.011. Epub 2018 Feb 16.

Abstract

Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C. The counts were integrated into a classical mathematical decline equation. After injection, human cells were essentially located in the endomysium, then they disappeared progressively from D0 to D28. The final number of integrated human nuclei was grossly determined at D2 after injection, suggesting that no more efficient fusion between donor myoblasts and host fibers occurs after the resolution of the local damages created by needle insertion. Almost 1% of implanted human cells occupied a satellite-like cell niche. Our mathematical model validated by histological counting provided a reliable quantitative estimate of human myoblast survival and/or incorporation into SCID muscle fibers. Informations brought by histological labelling and this mathematical model are complementary.

摘要

细胞移植在多种遗传性或获得性肌肉疾病的临床适应证中受到挑战,但治疗效果并不理想。为了更好地理解和提高组织再生的效果,我们旨在模拟 CD56 阳性的人类成肌细胞移植后的命运。我们使用免疫缺陷的严重联合免疫缺陷(SCID)小鼠作为受体,通过对层粘连蛋白、肌营养不良蛋白和人层粘连蛋白 A/C 的三重免疫组织化学标记,评估了人类成肌细胞的存活、整合和卫星细胞龛占有率。计数结果被整合到一个经典的数学衰减方程中。注射后,人类细胞主要位于肌内膜中,然后从 D0 到 D28 逐渐消失。注射后 D2 时检测到的整合人类核数量大致确定,这表明在由针刺引起的局部损伤解决后,供体成肌细胞与宿主纤维之间不再发生更有效的融合。大约 1%的植入人类细胞占据了类似卫星的细胞龛位。我们通过组织学计数验证的数学模型,为人类成肌细胞的存活和/或整合到 SCID 肌肉纤维中提供了可靠的定量估计。组织学标记和这种数学模型提供的信息是互补的。

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