Cryopreserved allogenic fibroblast sheets: development of a promising treatment for refractory skin ulcers.
Cryopreserved allogenic fibroblast sheets: development of a promising treatment for refractory skin ulcers.
复制标题
DOI：
--
复制
发表时间：
2022
影响因子：
2.2
通讯作者：
Soichi Ike;Koji Ueno;Masashi Yanagihara;T. Mizoguchi;Takasuke Harada;K. Suehiro;H. Kurazumi;R. Suzuki;T. Kondo;Tomoaki Murata;B. Shirasawa;N. Morikage;K. Hamano
中科院分区：
文献类型：
--
作者：
Soichi Ike;Koji Ueno;Masashi Yanagihara;T. Mizoguchi;Takasuke Harada;K. Suehiro;H. Kurazumi;R. Suzuki;T. Kondo;Tomoaki Murata;B. Shirasawa;N. Morikage;K. Hamano
本研究的目的是探讨冷冻保存的同种异体成纤维细胞对小鼠皮肤溃疡模型的治疗效果。为使再生医学得到广泛应用，有必要降低其成本。我们认为，如果同种异体细胞片能够冷冻保存，细胞片可以应用于各种疾病。在这项研究中，成纤维细胞被用三维冷冻机冷冻。冻融成纤维细胞的细胞存活率约为80%，其分泌的≥血管内皮生长因子、肝细胞生长因子和基质衍生因子-1α为未冻成纤维细胞片的50%，转化生长因子-β-1的分泌量与未冻融成纤维细胞片大致相同。自体细胞和同种异体细胞的血管生成程度相当。与自体成纤维细胞片相比，同种异体成纤维细胞片愈合组织中CD3阳性细胞数量较多。然而，组织病理学图像显示，同种异体冻融成纤维细胞片的纤维化、微血管密度和愈合期与自体冻融成纤维细胞片更接近于同种异体未冷冻成纤维细胞片。这些结果表明，同种异体冻融成纤维细胞片可能是治疗难治性皮肤溃疡的一种有前途的选择。
The purpose of this study was to investigate the therapeutic effect of cryopreserved allogenic fibroblast cell sheets in a mouse model of skin ulcers. It is necessary to reduce the cost of regenerative medicine for it to be widely used. We consider that cell sheets could be applied to various diseases if cryopreservation of allogenic cell sheets was possible. In this study, fibroblasts were frozen using a three-dimensional freezer. Freeze-thawed fibroblasts had ~80% cell viability, secreted ≥ 50% vascular endothelial growth factor, hepatocyte growth factor, and stromal derived factor-1α compared with non-frozen fibroblast sheets, and secreted approximately the same amount of transforming growth factor-β1. There was no difference in wound-healing rates in the skin ulcer model between non-frozen and freeze-thawed fibroblast sheets regardless of autologous and allogenic cells. The degree of angiogenesis was comparable between autologous and allogenic cells. The number of CD3-positive cells in healed tissues was larger for allogenic fibroblast sheets compared with autologous fibroblast sheets. However, histopathological images showed that the fibrosis, microvascular density, and healing phase of the wound in allogenic freeze-thawed fibroblast sheets were more similar to autologous freeze-thawed fibroblast sheets than to allogenic non-frozen fibroblast sheets. These results suggest that allogenic freeze-thawed fibroblast sheets may be a promising therapeutic option for refractory skin ulcers.