Genetically modified skin to treat disease: potential and limitations.
Genetically modified skin to treat disease: potential and limitations.
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转基因皮肤治疗疾病：潜力和局限性。
DOI：
10.1038/jid.1994.14
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
M. Petersen
中科院分区：
文献类型：
--
作者：
G. Krueger;J. Morgan;C. M. Jorgensen;L. Schmidt;H. L. Li;M. Kwan;S. Boyce;H. Wiley;J. Kaplan;M. Petersen
在基因水平上对疾病的分子定义和重组DNA技术的进展表明，许多疾病可以通过不携带导致疾病的缺陷元件的基因进行纠正。在这种疗法用于纠正慢性病之前，必须回答许多问题。这些问题属于安全性和有效性类别。将皮肤细胞成分或皮肤替代品（定义为具有细胞类型和真皮结构以发育成功能性皮肤的皮肤）移植到无胸腺啮齿动物的经验相当多，并且被视为可以回答这些问题的系统。本文综述了这些问题，并介绍了我们的早期分析，在体内和体外皮肤替代品的转基因细胞。实验数据表明，容纳成纤维细胞产生的胶原蛋白的编织尼龙基质和死真皮都可以用于将遗传修饰的人成纤维细胞从实验室穿梭到体内环境。基因修饰的成纤维细胞不会从穿梭细胞迁移到周围组织。大量（约70%）遗传修饰的成纤维细胞在这些穿梭中存活至少6周，支持这种具有临床实用性的一般方法。它也可以得出结论，皮肤替代系统可以用来产生一个基因修饰的皮肤在体外，有能力发展成功能性皮肤在体内。此外，随着遗传修饰的角质形成细胞分化，转基因的产量增加，支持角质形成细胞具有作为治疗基因穿梭体的真正潜力的概念。这项工作表明，含有皮肤基因修饰细胞的系统的移植可用于实验性地定义使用皮肤的基因治疗的许多方面，然后将该技术应用于临床。实例包括确定基因转导和表达对遗传修饰的皮肤的结构和功能以及对远处皮肤的影响，以及评估转基因的翻译能力作为时间和细胞数量的函数。
Molecular definition of disease at the level of the gene and advances in recombinant DNA technology suggest that many diseases are amenable to correction by genes not bearing the defective elements that result in disease. Many questions must be answered before this therapy can be used to correct chronic diseases. These questions fall into safety and efficacy categories. Experience with transplanting cellular elements of skin or skin substitutes (defined as skin that possess the cell types and a dermal structure to develop into a functioning skin) to athymic rodents is considerable and is seen as a system where these questions can be answered. This paper reviews these questions and presents our early analysis of genetically modified cells in skin substitutes in vivo and in vitro. Experimental data demonstrate that both a matrix of woven nylon, housing a fibroblast generated collage, and dead dermis can be utilized to shuttle genetically modified human fibroblasts from the laboratory to an in vivo setting. Genetically modified fibroblasts do not migrate from the shuttle to the surrounding tissue. The survival of significant numbers, approximately 70%, of genetically modified fibroblasts for at least 6 weeks in these shuttles, supports this general approach as having clinical utility. It is also concluded that skin substitute systems can be used to generate a genetically modified skin in vitro that has the capacity to develop into functional skin in vivo. Further, as genetically modified keratinocytes differentiate there is increased production by the transgene, supporting the concept that keratinocytes have true potential as shuttles for therapeutic genes. This work demonstrates that transplantation of systems containing genetically modified cells of the skin can be used to experimentally define many aspects of gene therapy using skin before this technology is taken to the clinic. Examples include determining the effect of gene transduction and expression on structure and function of the genetically modified skin as well as on distant skin and an assessment of the translational capacity of the transgene as function of time and cell number.
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DOI：
10.1002/jbm.820221008
发表时间：
1988-10-01
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子：
--
作者：
BOYCE, ST;CHRISTIANSON, DJ;HANSBROUGH, JF
通讯作者：
HANSBROUGH, JF
转基因小鼠表皮过度表达转化生长因子β1抑制皮肤发育。
DOI：
10.1073/pnas.90.11.5237
发表时间：
1993
影响因子：
11.1
作者：
Sellheyer,K;Bickenbach,JR;Rothnagel,JA;Bundman,D;Longley,MA;Krieg,T;Roche,NS;Roberts,AB;Roop,DR
通讯作者：
Roop,DR
影响因子：
56.9
作者：
DHAWAN, J;PAN, LC;BLAU, HM
通讯作者：
BLAU, HM
可移植的人表皮细胞表达外源生长激素基因。
DOI：
10.1126/science.3629250
发表时间：
1987
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Morgan,JR;Barrandon,Y;Green,H;Mulligan,RC
通讯作者：
Mulligan,RC
影响因子：
6.5
作者：
LANGDON, RC;CUONO, CB;MOELLMANN, GE
通讯作者：
MOELLMANN, GE