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从兔胎肝中分离的间充质干细胞的鉴定。

Characterization of mesenchymal stem cells isolated from the rabbit fetal liver.

机构信息

Medical and Molecular Genetics Center, Institut d'Investigació Biomèdica de Bellvitge, Barcelona, Spain.

出版信息

Stem Cells Dev. 2010 Oct;19(10):1579-88. doi: 10.1089/scd.2009.0514.

Abstract

Physiological attributes of mesenchymal stem cells (MSCs) including straightforward manipulation, multilineage differentiation, immunoregulation, and tropism for injury settings render them ideal therapeutic agents for tissue repair/regeneration. Nevertheless, further studies in suitable animal models of disease are needed to translate the potential of MSCs into clinical applications. We report here the isolation and preliminary characterization of MSCs from fetal rabbit liver (fl-MSCs). Compared with MSCs isolated from adult rabbit bone marrow, fl-MSCs had superior growth rate, clonogenic capability, and plastic adherence owing to their developmental immaturity. Both cytochemical staining and mRNA expression analysis of fl-MSCs confirmed mesodermal lineage differentiation into adipocytes, osteocytes, and chondrocytes. Moreover, fl-MSCs were capable to prevent lymphocyte proliferation both in a 2-way MLC and upon phytohemagglutinin (PHA) stimulation. In contrast, fl-MSCs co-cultured with allogeneic lymphocytes induced proliferation of the latter. Relatedly, although freshly isolated fl-MSCs did express neither major histocompatibility complex (MHC) class I/II nor CD80/CD86, all these immune synapse components were induced upon in vitro culture. Furthermore, fl-MSCs became efficiently transduced for long-term transgene expression with a retroviral vector. Thus, the special biological qualities of fl-MSCs endow them as model candidate vehicles/agents for gene/cell therapy strategies applied to a variety of rabbit models of injury, such as osteochondral lesions.

摘要

间充质干细胞(MSCs)具有易于操作、多向分化、免疫调节和向损伤部位归巢等生理特性,使其成为组织修复/再生的理想治疗剂。然而,需要在合适的疾病动物模型中进一步研究,才能将 MSCs 的潜力转化为临床应用。我们在此报告了从胎兔肝脏(fl-MSCs)中分离和初步鉴定 MSCs。与从成年兔骨髓中分离的 MSCs 相比,fl-MSCs 由于发育不成熟,具有更高的生长速度、克隆形成能力和塑料贴附能力。fl-MSCs 的细胞化学染色和 mRNA 表达分析均证实其向脂肪细胞、成骨细胞和软骨细胞的中胚层谱系分化。此外,fl-MSCs 能够在双向混合淋巴细胞培养(MLC)和植物血凝素(PHA)刺激下防止淋巴细胞增殖。相反,fl-MSCs 与同种异体淋巴细胞共培养后,后者增殖。相关地,尽管新鲜分离的 fl-MSCs 既不表达主要组织相容性复合体(MHC)I/II 类分子,也不表达 CD80/CD86,但所有这些免疫突触成分在体外培养时均被诱导表达。此外,fl-MSCs 可以被逆转录病毒载体高效转导,实现长期转基因表达。因此,fl-MSCs 的特殊生物学特性使它们成为基因/细胞治疗策略的候选载体/药物,可应用于多种兔损伤模型,如骨软骨损伤。

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