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间充质基质细胞用于兔模型皮肤伤口愈合:适用于小儿外科手术环境的临床前研究

Mesenchymal stromal cells for cutaneous wound healing in a rabbit model: pre-clinical study applicable in the pediatric surgical setting.

作者信息

Pelizzo Gloria, Avanzini Maria Antonietta, Icaro Cornaglia Antonia, Osti Monica, Romano Piero, Avolio Luigi, Maccario Rita, Dominici Massimo, De Silvestri Annalisa, Andreatta Erika, Costanzo Federico, Mantelli Melissa, Ingo Daniela, Piccinno Serena, Calcaterra Valeria

机构信息

Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy.

Immunology and Transplantation Laboratory/Cell Factory/Pediatric Hematology/Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

出版信息

J Transl Med. 2015 Jul 8;13:219. doi: 10.1186/s12967-015-0580-3.

Abstract

OBJECTIVE

Mesenchymal stromal cells (MSCs) expanded in vitro have been proposed as a potential therapy for congenital or acquired skin defects in pediatrics. The aim of this pre-clinical study was to investigate the effects of intradermal injections of MSC in experimental cutaneous wound repair comparing allogeneic and autologous adipose stem cells (ASCs) and autologous bone marrow-mesenchymal stromal cells (BM-MSCs).

METHODS

Mesenchymal stromal cells were in vitro expanded from adipose and BM tissues of young female New Zealand rabbits. MSCs were characterized for plastic adhesion, surface markers, proliferation and differentiation capacity. When an adequate number of cells (ASCs 10 × 10(6) and BM-MSCs 3 × 10(6), because of their low rate of proliferation) was reached, two skin wounds were surgically induced in each animal. The first was topically treated with cell infusions, the second was used as a control. The intradermal inoculation included autologous or allogeneic ASCs or autologous BM-MSCs. For histological examination, animals were sacrificed and wounds were harvested after 11 and 21 days of treatment.

RESULTS

Rabbit ASCs were isolated and expanded in vitro with relative abundance, cells expressed typical surface markers (CD49e, CD90 and CD29). Topically, ASC inoculation provided more rapid wound healing than BM-MSCs and controls. Improved re-epithelization, reduced inflammatory infiltration and increased collagen deposition were observed in biopsies from wounds treated with ASCs, with the best result in the autologous setting. ASCs also improved restoration of skin architecture during wound healing.

CONCLUSION

The use of ASCs may offer a promising solution to treat extended wounds. Pre-clinical studies are however necessary to validate the best skin regeneration technique, which could be used in pediatric surgical translational research.

摘要

目的

体外扩增的间充质基质细胞(MSC)已被提议作为治疗儿科先天性或获得性皮肤缺损的一种潜在疗法。这项临床前研究的目的是比较同种异体和自体脂肪干细胞(ASC)以及自体骨髓间充质基质细胞(BM-MSC)皮内注射MSC对实验性皮肤伤口修复的影响。

方法

从年轻雌性新西兰兔的脂肪和骨髓组织中体外扩增间充质基质细胞。对MSC进行塑料黏附、表面标志物、增殖和分化能力的鉴定。当达到足够数量的细胞(ASC为10×10⁶,BM-MSC为3×10⁶,因其增殖率低)时,对每只动物进行手术造成两处皮肤伤口。第一处伤口局部用细胞输注治疗,第二处作为对照。皮内接种包括自体或同种异体ASC或自体BM-MSC。为进行组织学检查,在治疗11天和21天后处死动物并采集伤口。

结果

兔ASC在体外相对丰富地分离和扩增,细胞表达典型的表面标志物(CD49e、CD90和CD29)。局部而言,ASC接种比BM-MSC和对照能使伤口愈合更快。在用ASC治疗的伤口活检中观察到再上皮化改善、炎症浸润减少和胶原沉积增加,在自体情况下效果最佳。ASC还改善了伤口愈合过程中皮肤结构的恢复。

结论

使用ASC可能为治疗大面积伤口提供一个有前景的解决方案。然而,需要进行临床前研究来验证最佳的皮肤再生技术,该技术可用于儿科外科转化研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6541/4495634/9f35b65aa9c6/12967_2015_580_Fig1_HTML.jpg

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