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用于抑制失巢凋亡并增强人间充质干细胞伤口愈合功效的羧甲基纤维素-聚乳酸颗粒

Carboxymethyl cellulose-polylactic acid particles for inhibiting anoikis and enhancing wound healing efficacy of human mesenchymal stem cells.

作者信息

Lee Dong-Hyun, Lee You Bin, Park Hyun Su, Jang Young-Ju, Kim Youn Chul, Bhang Suk Ho

机构信息

School of Chemical Engineering Sungkyunkwan University (SKKU) Suwon Gyeonggi-do Republic of Korea.

出版信息

Bioeng Transl Med. 2025 Feb 12;10(4):e70003. doi: 10.1002/btm2.70003. eCollection 2025 Jul.

Abstract

Adult human mesenchymal stem cells (hMSCs) injection into the wound site promotes angiogenesis and the wound-closing process by secreting various growth and immune-modulating factors. However, lower cell attachment sites and the hypoxic microenvironment in the wound site limit their viability and engraftment rate, leading to programmed cell death, anoikis. We synthesized carboxymethyl cellulose-coated polylactic acid (CMC-PLA) particles to prevent anoikis by providing an attachable surface for hMSCs. In vitro experiments demonstrated enhanced viability and secretion of growth factors by hMSCs under severely hypoxic microenvironments, when CMC-PLA particles provided attachment surfaces, compared to controls. Furthermore, in vivo experiments showed that CMC-PLA particles injected with hMSCs improved collagen synthesis and wound closure more than those of the control groups. These findings suggest that CMC-PLA particles effectively enhance the therapeutic potential of hMSCs by providing a supportive microenvironment, promoting cell survival, proliferation, and angiogenesis, thereby offering a promising approach for advanced wound healing therapies.

摘要

将成人人类间充质干细胞(hMSCs)注射到伤口部位,可通过分泌多种生长因子和免疫调节因子促进血管生成和伤口愈合过程。然而,伤口部位较低的细胞附着位点和缺氧微环境限制了它们的活力和植入率,导致程序性细胞死亡,即失巢凋亡。我们合成了羧甲基纤维素包被的聚乳酸(CMC-PLA)颗粒,通过为hMSCs提供可附着表面来防止失巢凋亡。体外实验表明,在严重缺氧微环境下,当CMC-PLA颗粒提供附着表面时,hMSCs的活力增强且生长因子分泌增加,与对照组相比有显著差异。此外,体内实验表明,与对照组相比,注射了hMSCs的CMC-PLA颗粒能更好地促进胶原蛋白合成和伤口愈合。这些发现表明,CMC-PLA颗粒通过提供支持性微环境,有效增强了hMSCs的治疗潜力,促进了细胞存活、增殖和血管生成,从而为先进的伤口愈合治疗提供了一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf7f/12284428/1ebe731b6fdc/BTM2-10-e70003-g003.jpg

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