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骨髓源猪间充质基质细胞的分离与体外扩增:在大型动物实体器官移植实验模型中的应用潜力

Isolation and ex vivo expansion of bone marrow-derived porcine mesenchymal stromal cells: potential for application in an experimental model of solid organ transplantation in large animals.

作者信息

Comite P, Cobianchi L, Avanzini M A, Zonta S, Mantelli M, Achille V, De Martino M, Cansolino L, Ferrari C, Alessiani M, Maccario R, Gandolfo G M, Dionigi P, Locatelli F, Bernardo M E

机构信息

Dipartimento di Medicina Sperimentale, Sapienza, Università degli Studi di Roma, Italy.

出版信息

Transplant Proc. 2010 May;42(4):1341-3. doi: 10.1016/j.transproceed.2010.03.080.

DOI:10.1016/j.transproceed.2010.03.080
PMID:20534296
Abstract

Pharmacological aspecific immunosuppression, despite being widely used in solid organ transplantation recipients, is unable to completely prevent allograft rejection. It promotes the occurrence of sometimes life-threatening infections. Due to their immunosuppressive and anti- inflammatory properties, there is great interest in the therapeutic use of bone marrow (BM)-derived mesenchymal stromal cells (MSC). Large animal models play a crucial role to investigate the biological and functional properties of MSCs as novel cellular therapy. In the current study we sought to isolate expand ex vivo, and phenotypically characterize MSC derived from BM of 4 Large White 6-month-old piglets. Porcine MSC (pMSC) were characterized for their in vitro differentiation capacity. pMSC were successfully isolated from all BM samples. They showed spindle-shaped morphology and a stable doubling time on culture. They were positive for CD90, CD29, CD105, and negative for CD45 and CD11b. Furthermore, they differentiated, upon specific in vitro conditions toward adipogenic and osteogenic lineages. The optimization of methods for the isolation and characterization of pMSC may be useful to elucidate their biological and functional properties. The anatomy and physiology of the pig, which is similar to humans, make this animal model more attractive than small animals to test the safety and efficacy of MSC in the context of solid organ transplantation.

摘要

尽管非特异性药理免疫抑制在实体器官移植受者中被广泛应用,但它无法完全预防同种异体移植排斥反应。它还会促使有时会危及生命的感染发生。由于其免疫抑制和抗炎特性,骨髓(BM)来源的间充质基质细胞(MSC)的治疗用途备受关注。大型动物模型在研究MSC作为新型细胞疗法的生物学和功能特性方面起着至关重要的作用。在本研究中,我们试图从4只6月龄大白仔猪的骨髓中体外分离、扩增并对MSC进行表型特征分析。对猪MSC(pMSC)的体外分化能力进行了表征。pMSC成功地从所有骨髓样本中分离出来。它们呈现纺锤形形态,在培养时具有稳定的倍增时间。它们CD90、CD29、CD105呈阳性,CD45和CD11b呈阴性。此外,在特定的体外条件下,它们可向脂肪生成和成骨谱系分化。优化pMSC的分离和表征方法可能有助于阐明其生物学和功能特性。猪的解剖学和生理学与人类相似,这使得该动物模型在测试MSC在实体器官移植中的安全性和有效性方面比小型动物更具吸引力。

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