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脂肪来源干细胞促进血管生成和组织形成,用于体内组织工程。

Adipose-derived stem cells promote angiogenesis and tissue formation for in vivo tissue engineering.

机构信息

O'Brien Institute, Fitzroy, Victoria, Australia.

出版信息

Tissue Eng Part A. 2013 Jun;19(11-12):1327-35. doi: 10.1089/ten.TEA.2012.0391. Epub 2013 Mar 28.

Abstract

Adult mesenchymal stem cells secrete a variety of angiogenic cytokines and growth factors, so we proposed that these paracrine mechanisms may be used to promote vascularization and growth for tissue engineering in vivo. We tested whether or not human adipose-derived stem cells (ASCs) promote tissue formation in rats. ASCs were evaluated in vitro for mRNA expression of angiogenic factors, including the vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8 (IL-8), and stromal cell-derived factor-1 (SDF-1) and proliferative activity on human microvascular endothelial cells. For in vivo analysis, CM-DiI-labeled ASCs were implanted with a rat cardiac extracellular matrix (ECM) extract-derived hydrogel into a chamber with a femoral arteriovenous loop in the groin of male nude rats for 7 days. Vascularization in newly generated tissue was estimated by histomorphometry after endothelial nitric oxide synthase (eNOS) immunostaining. ASCs expressed growth factor mRNA and produced an angiogenic activity in vitro. After implantation, ASCs survived, but remained suspended in the ECM and relatively few were incorporated into the newly formed tissue. The volume of newly generated tissue was significantly higher in chambers containing ASCs and it was enriched with vasculature when compared with the ECM alone. We conclude that human ASCs promote tissue growth and angiogenesis in the rat vascularized chamber, thereby showing promise for tissue-engineering applications for regenerative therapy.

摘要

成体间充质干细胞分泌多种血管生成细胞因子和生长因子,因此我们提出这些旁分泌机制可能被用于促进体内组织工程的血管化和生长。我们检测了人脂肪来源的干细胞(ASCs)是否能促进大鼠组织的形成。我们在体外评估了 ASC 血管生成因子的 mRNA 表达,包括血管内皮生长因子、碱性成纤维细胞生长因子、白细胞介素-8(IL-8)和基质细胞衍生因子-1(SDF-1),以及对人微血管内皮细胞的增殖活性。为了进行体内分析,CM-DiI 标记的 ASC 与大鼠心脏细胞外基质(ECM)提取物衍生的水凝胶一起植入腹股沟带有股动静脉环的腔室内,在雄性裸鼠体内 7 天。通过内皮型一氧化氮合酶(eNOS)免疫染色后对新生成组织中的血管化进行组织形态计量学评估。ASC 表达生长因子 mRNA 并在体外产生血管生成活性。植入后,ASC 存活,但仍悬浮在 ECM 中,并且很少被整合到新形成的组织中。与单独的 ECM 相比,含有 ASC 的腔室内新生成组织的体积明显更高,并且富含血管。我们的结论是,人 ASC 促进了大鼠血管化腔室内的组织生长和血管生成,从而为再生治疗的组织工程应用提供了希望。

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