EFFECTIVE USE OF MESENCHYMAL STEM CELLS IN HUMAN SKIN SUBSTITUTES GENERATED BY TISSUE ENGINEERING
EFFECTIVE USE OF MESENCHYMAL STEM CELLS IN HUMAN SKIN SUBSTITUTES GENERATED BY TISSUE ENGINEERING
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DOI：
10.22203/ecm.v037a14
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发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
Garzon, I
中科院分区：
文献类型：
--
作者：
Martin-Piedra, M. A.;Alfonso-Rodriguez, C. A.;Garzon, I
间充质干细胞(MSCs)可以向上皮细胞分化，可作为异型人工皮肤替代物的替代来源，从而增强其发育和移植到临床的潜力。本研究旨在比较四种类型的异型人类生物工程皮肤，使用骨髓间充质干细胞作为替代上皮细胞来源。将脂肪组织来源的干细胞(ADSCs)、牙髓干细胞(DPSCs)、Wharton的凝胶干细胞(WJSCs)和骨髓干细胞(BMSCs)用于真皮替代物上的表皮再生。将异型人皮肤替代物植入免疫缺陷裸鼠体内30d，进行组织学和遗传学研究，观察细胞外基质合成、表皮分化和人类白细胞抗原(人类白细胞抗原)分子的表达。移植后30d细胞角蛋白10和微丝蛋白的表达显示四种细胞均分化为角质形成细胞，并以相似的方式诱导真皮成纤维细胞合成细胞外纤维成分和非纤维成分。WJSCs和BMSCs有较高的细胞角蛋白10和微丝蛋白表达，提示这些细胞更倾向于表皮再生。即使当上皮层分化时，也不存在HLA分子，这支持了这些替代品--特别是ADSCs、DPSCs和WJSCs--未来的临床应用，而且排斥风险很低。MSCs使具有潜在临床用途的生物工程化人类皮肤替代品的产生成为可能。鉴于WJSCs的表皮分化潜能和缺乏HLA抗原，应优先使用WJSCs。
Mesenchymal stem cells (MSCs) can differentiate toward epithelial cells and may be used as an alternative source for generation of heterotypical artificial human skin substitutes, thus, enhancing their development and translation potential to the clinic. The present study aimed at comparing four types of heterotypical human bioengineered skin generated using MSCs as an alternative epithelial cell source. Adipose-tissue-derived stem cells (ADSCs), dental pulp stem cells (DPSCs), Wharton's jelly stem cells (WJSCs) and bone marrow stem cells (BMSCs) were used for epidermal regeneration on top of dermal skin substitutes. Heterotypic human skin substitutes were evaluated before and after implantation in immune-deficient athymic mice for 30 d. Histological and genetic studies were performed to evaluate extracellular matrix synthesis, epidermal differentiation and human leukocyte antigen (HLA) molecule expression. The four cell types differentiated into keratinocytes, as shown by the expression of cytokeratin 10 and filaggrin 30 d post-grafting; also, they induced dermal fibroblasts responsible for the synthesis of extracellular fibrillar and non-fibrillar components, in a similar way among each other. WJSCs and BMSCs showed higher expression of cytokeratin 10 and filaggrin, suggesting these cells were more prone to epidermal regeneration. The absence of HLA molecules, even when the epithelial layer was differentiated, supports the future clinical use of these substitutes - especially ADSCs, DPSCs and WJSCs - with low rejection risk. MSCs allowed the generation of bioengineered human skin substitutes with potential clinical usefulness. According to their epidermal differentiation potential and lack of HLA antigens, WJSCs should preferentially be used.