Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan.
Department of Plastic Surgery, University of Tokyo, School of Medicine, Tokyo, Japan.
J Tissue Eng Regen Med. 2018 May;12(5):1186-1194. doi: 10.1002/term.2647. Epub 2018 Mar 4.
Chronic changes following radiotherapy include alterations in tissue-resident stem cells and vasculatures, which can lead to impaired wound healing. In this study, novel recombinant human collagen peptide (rhCP) scaffolds were evaluated as a biomaterial carrier for cellular regenerative therapy. Human adipose-derived stem cells (hASCs) were successfully cultured on rhCP scaffolds. By hASC culture on rhCP, microarray assay indicated that expression of genes related to cell proliferation and extracellular matrix production was upregulated. Pathway analyses revealed that signaling pathways related to inflammatory suppression and cell growth promotion were activated as well as signaling pathways consistent with some growth factors including vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor beta, although gene expression of these growth factors was not upregulated. These findings suggest the rhCP scaffold showed similar biological actions to cytokines regulating cell growth and immunity. In subsequent impaired wound healing experiments using a locally irradiated (20 Gray) mouse, wound treatment with rhCP sponges combined with cultured hASCs and human umbilical vein endothelial cells accelerated wound closure compared with wounds treated with rhCP with hASCs alone, rhCP only, and control (dressing alone), with better healing observed according to this order. These results indicating the therapeutic value of rhCP scaffolds as a topical biomaterial dressing and a biocarrier of stem cells and vascular endothelial cells for regenerating therapies. The combination of rhCP and functional cells was suggested to be a potential tool for revitalizing stem cell-depleted conditions such as radiation tissue damage.
放疗后的慢性变化包括组织驻留干细胞和脉管系统的改变,这可能导致伤口愈合受损。在这项研究中,新型重组人胶原蛋白肽 (rhCP) 支架被评估为细胞再生治疗的生物材料载体。人脂肪来源的干细胞 (hASC) 成功地在 rhCP 支架上培养。通过 hASC 在 rhCP 上的培养,微阵列分析表明与细胞增殖和细胞外基质产生相关的基因表达上调。通路分析表明,与炎症抑制和细胞生长促进相关的信号通路被激活,与包括血管内皮生长因子、肝细胞生长因子和转化生长因子 β 在内的一些生长因子的信号通路一致,尽管这些生长因子的基因表达没有上调。这些发现表明 rhCP 支架表现出与调节细胞生长和免疫的细胞因子相似的生物学作用。在随后使用局部照射(20Gy)的小鼠进行的受损伤口愈合实验中,rhCP 海绵联合培养的 hASC 和人脐静脉内皮细胞处理的伤口与单独使用 rhCP 与 hASC 处理的伤口、仅使用 rhCP 处理的伤口和对照组(单独敷料)相比,伤口闭合更快,按照这个顺序观察到更好的愈合。这些结果表明 rhCP 支架作为局部生物材料敷料和干细胞和血管内皮细胞的生物载体用于再生治疗具有治疗价值。rhCP 与功能细胞的组合被认为是一种潜在的工具,可以恢复如辐射组织损伤等干细胞耗竭的情况。
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