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通过功能化的等离子体聚合表面递送多能成体祖细胞可加速小鼠糖尿病伤口的愈合。

Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds.

作者信息

Mills S J, Kirby G T, Hofma B R, Smith L E, Statham P, Vaes B, Ting A E, Short R, Cowin A J

机构信息

Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia.

Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia.

出版信息

Front Bioeng Biotechnol. 2023 Aug 22;11:1213021. doi: 10.3389/fbioe.2023.1213021. eCollection 2023.

Abstract

Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

摘要

干细胞疗法已被作为慢性伤口的潜在治疗方式进行研究,然而迄今为止取得的成功有限。多能成人祖细胞(MAPCs©)已被确定有潜力成为一种同种异体干细胞产品,因为它们具有高群体倍增数,以及抑制T细胞增殖的特性。这有助于预防自身免疫和移植物/细胞排斥。我们开发了一种敷料,由涂有庚胺等离子体聚合物的医用级硅酮组成,它能支持MAPCs向皮肤的生长和转移。为了确定该敷料能否将功能性干细胞输送到糖尿病伤口中,将其装载MAPCs后放置在正常和糖尿病小鼠的切除伤口上。在正常和糖尿病伤口中均观察到愈合加速,与对照组相比,第3天时伤口裂开明显更小。伤口分析表明,用MAPC敷料治疗可减轻炎症反应,观察到中性粒细胞和巨噬细胞数量减少。此外,观察到促血管生成的VEGF和CD31阳性内皮细胞增加,表明新血管形成得到改善。MAPC敷料对纤维化没有影响,I型和III型胶原蛋白在对照伤口和处理伤口中受到的影响相同。总体而言,功能化的MAPC敷料可改善愈合反应,尤其是在愈合反应受损的糖尿病小鼠中,因此,显示出作为治疗慢性糖尿病伤口的先进治疗方法的开发潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f55/10477914/aec167dce1b6/fbioe-11-1213021-g001.jpg

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