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通过聚酰胺/壳聚糖表面实现pH驱动的具有增强再生能力的连续干细胞生产。

pH-driven continuous stem cell production with enhanced regenerative capacity from polyamide/chitosan surfaces.

作者信息

Yen Chia-Hsiang, Cheng Nai-Chen, Hsieh Hao-Ying, Tsai Ching-Wen, Lee An-Li, Lu Chien-Yi, Chen Yin-Tzu, Young Tai-Horng

机构信息

Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd., Taipei, 100, Taiwan.

Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan S Rd., Taipei, 100, Taiwan.

出版信息

Mater Today Bio. 2022 Dec 7;18:100514. doi: 10.1016/j.mtbio.2022.100514. eCollection 2023 Feb.

Abstract

Adipose-derived stem cells (ASCs) have raised significant interest for their potential therapeutic applications in regenerative medicine. However, ASCs usually suffer from decreased pluripotency and functional plasticity during expansion. Herein, this study sought to develop a continuous cell production system that can mass-produce ASCs with sustained regenerative capacity. The strategy was blending pH-responsive chitosan (CS) with polyamide-66 (PA) to generate combined surface properties with controllable cell growth/detachment ability to achieve a repeated cell production process. From the collected data, all the polymer blends were capable of completing a minimum of four consecutive production cycles, wherein the PA17CS blend (PA:CS 1:7) outperformed with respect to the working effectiveness (average cell detachment ratio 88%) and the cell viability. Compared to the trypsin-based method, ASCs harvested from PA17CS exhibited superior stemness characteristics along with SDF-1-mediated CXCR4 chemotactic response for stem cell homing. Moreover, injection of ASCs generated from PA17CS blend could more effectively induce neovascularization and protect skin flaps during an ischemic injury in a rat model.

摘要

脂肪来源干细胞(ASCs)因其在再生医学中的潜在治疗应用而引起了广泛关注。然而,ASCs在扩增过程中通常会出现多能性和功能可塑性下降的问题。在此,本研究旨在开发一种连续细胞生产系统,该系统能够大量生产具有持续再生能力的ASCs。策略是将pH响应性壳聚糖(CS)与聚酰胺-66(PA)混合,以产生具有可控细胞生长/脱离能力的组合表面特性,从而实现重复的细胞生产过程。从收集的数据来看,所有聚合物共混物都能够完成至少四个连续的生产周期,其中PA17CS共混物(PA:CS 1:7)在工作效率(平均细胞脱离率88%)和细胞活力方面表现更优。与基于胰蛋白酶的方法相比,从PA17CS收获的ASCs表现出更优异的干性特征以及SDF-1介导的用于干细胞归巢的CXCR4趋化反应。此外,在大鼠模型的缺血性损伤期间,注射由PA17CS共混物产生的ASCs能够更有效地诱导新血管形成并保护皮瓣。

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