CELL TRANSPLANTATION OF GENETICALLY ALTERED CELLS ON BIODEGRADABLE POLYMER SCAFFOLDS IN SYNGENEIC RATS
CELL TRANSPLANTATION OF GENETICALLY ALTERED CELLS ON BIODEGRADABLE POLYMER SCAFFOLDS IN SYNGENEIC RATS
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DOI：
10.1097/00007890-199308000-00033
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发表时间：
1993-08-01
期刊：
影响因子：
6.2
通讯作者：
VACANTI, JP
中科院分区：
文献类型：
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作者：
GILBERT, JC;TAKADA, T;VACANTI, JP
儿童中许多严重的代谢缺陷是由单基因缺陷以及由此产生的单基因产物缺陷引起的。使用基因转移和细胞移植新技术可能可以永久治愈这些疾病。在逆转录病毒介导的基因治疗的许多体内模型中，一个重要的限制因素是移植足够数量的修饰细胞的能力。为了潜在地规避这个问题，我们开发了一种可生物降解的聚合物植入系统，能够支持大量转基因细胞。在这项研究中，我们将报告基因插入同系培养的正常成纤维细胞中，然后使用合成的可生物降解聚合物纤维作为临时细胞递送支架将这些转基因细胞移植到动物体内。为了开始开发能够传递转基因细胞分泌的所需蛋白质的系统，使用含有报告基因 Lac Z 的逆转录病毒在组织培养物中转导 Fischer 344 成年大鼠成纤维细胞。然后将这些转基因细胞（1.1X10(7) 细胞/移植物）附着到可生物降解的聚合物纤维上，并将聚合物细胞移植物进行移植 皮下注射到同基因受体中（n = 9）。报告基因表达的修饰细胞持续存在至少 30 天。每个植入移植物的估计转基因细胞数量在移植后15天从移植前的1.1+/-0.6x10(7)减少到3.2+/-0.7x10(6) (P0.2)。这些数据表明，使用可生物降解的聚合物纤维可以允许移植足够数量的转基因细胞以提供治疗有用的产品。聚合物基质允许转基因细胞的附着和位点特异性移植。
Many severe metabolic deficiencies in children are caused by a single gene defect with a resultant single gene product deficiency. These diseases may be amenable to permanent cure using new techniques of gene transfer and cell transplantation. In many in vivo models of retroviral mediated gene therapy, a significant limiting factor is the ability to transplant a sufficient number of modified cells. To potentially circumvent this problem, we have developed a biodegradable polymer implant system capable of supporting large numbers of genetically modified cells. In this study, we inserted a reporter gene into syngeneic cultured normal fibroblasts and then transplanted these genetically modified cells into animals using synthetic biodegradable polymer fibers as temporary cell delivery scaffolds. To begin to develop a system capable of delivering desirable proteins secreted by genetically modified cells, Fischer 344 adult rat fibroblasts were transduced in tissue culture with a retrovirus containing the reporter gene Lac Z. These genetically modified cells (1.1X10(7) cells/graft) were then attached to the biodegradable polymer fibers and the polymer-cell graft was transplanted subdermally into syngeneic recipients (n=9). There was persistence of the modified cells with expression of the reporter gene for at least 30 days. The estimated number of genetically modified cells per implanted graft decreased from a pretransplant value of 1.1+/-0.6x10(7) to 3.2+/-0.7x10(6) by 15 days after transplantation (P0.2).These data suggest that the use of biodegradable polymer fibers may permit the transplantation of genetically modified cells in sufficient numbers to deliver a therapeutically useful product. Polymer matrices allow for the attachment and site-specific transplantation of genetically modified cells.