Spontaneous cell sorting of fibroblasts and keratinocytes creates an organotypic human skin equivalent.
Spontaneous cell sorting of fibroblasts and keratinocytes creates an organotypic human skin equivalent.
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成纤维细胞和角质形成细胞的自发细胞分选产生了人体皮肤的器官型等效物。
DOI：
10.1046/j.1523-1747.2000.00938.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Hoeffler,WK
中科院分区：
文献类型：
--
作者：
Wang,CK;Nelson,CF;Brinkman,AM;Miller,AC;Hoeffler,WK
我们表明，两种不同的细胞类型，角质形成细胞和成纤维细胞的固有能力，可以依赖于准确地重建全层人类皮肤，包括真皮表皮交界处的细胞分选机制。将含有两种细胞类型的细胞浆添加到植入严重联合免疫缺陷小鼠背部的硅胶室中，在2周内进行分选以重建明确定义的真皮和分层表皮，形成细胞分选的皮肤等同物。用人类细胞标记物对细胞分选的皮肤等同物进行免疫染色，显示出与正常全层皮肤相似的模式。我们比较了细胞分选的皮肤等效模型与也在严重联合免疫缺陷小鼠上制备的复合皮肤模型。复合移植物由部分分化的角质形成细胞片构成，置于由失活真皮构成的真皮等同物之上。电子显微镜显示，这两种模型形成了大量的正常出现的半桥粒。然而，细胞分选的皮肤等效模型，有更多数量的角蛋白中间丝内的基底角质形成细胞连接到半桥粒，并在真皮侧的胶原纤维和锚定纤维连接到致密层更多的复合模型相比。我们的研究结果可以提供一些见解，为什么在治疗烧伤和其他伤口的临床应用中，复合移植物可能会表现出表面不稳定性和起泡长达一年的移植后，并建议在未来的移植应用中的细胞分选皮肤等效物的可能用途。
We show that an inherent ability of two distinct cell types, keratinocytes and fibroblasts, can be relied upon to accurately reconstitute full-thickness human skin including the dermal-epidermal junction by a cell-sorting mechanism. A cell slurry containing both cell types added to silicone chambers implanted on the backs of severe combined immunodeficient mice sorts out to reconstitute a clearly defined dermis and stratified epidermis within 2 wk, forming a cell-sorted skin equivalent. Immunostaining of the cell-sorted skin equivalent with human cell markers showed patterns similar to those of normal full-thickness skin. We compared the cell-sorted skin equivalent model with a composite skin model also made on severe combined immunodeficient mice. The composite grafts were constructed from partially differentiated keratinocyte sheets placed on top of a dermal equivalent constructed of devitalized dermis. Electron microscopy revealed that both models formed ample numbers of normal appearing hemidesmosomes. The cell-sorted skin equivalent model, however, had greater numbers of keratin intermediate filaments within the basal keratinocytes that connected to hemidesmosomes, and on the dermal side both collagen filaments and anchoring fibril connections to the lamina densa were more numerous compared with the composite model. Our results may provide some insight into why, in clinical applications for treating burns and other wounds, composite grafts may exhibit surface instability and blistering for up to a year following grafting, and suggest the possible usefulness of the cell-sorted skin equivalent in future grafting applications.