Gene-activated fat grafts for the repair of spinal cord injury: a pilot study
Gene-activated fat grafts for the repair of spinal cord injury: a pilot study
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DOI：
10.1007/s00701-015-2626-y
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发表时间：
2016-02-01
影响因子：
2.4
通讯作者：
Kirsch, Matthias
中科院分区：
文献类型：
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作者：
Betz, Volker M.;Sitoci-Ficici, K. Hakan;Kirsch, Matthias
脊髓损伤是一种复杂的疾病，需要协调一致的多靶点治疗方法。治疗基因、细胞载体和空间填充支架的最合适组合仍有待确定。我们提出了一种采用同源脂肪组织作为三维生物植入物、祖细胞来源和治疗基因传递系统的方法。在这个先导实验中，我们评估了脊髓损伤后使用基因激活的自体脂肪移植的可行性和短期效果。采用T9-T10半髓系切除术建立同基因Fischer 344大鼠实验性脊髓损伤模型。从两只供体大鼠身上采集脂肪组织。动物被分为四组，分别接受(i)由携带人类NT-3 cDNA的腺病毒载体激活的脂肪移植物、（ii）或BDNF、（iii）或未经处理的脂肪移植物或（iv）不进行处理。术后7天或21天对动物实施安乐死，采用组织学和免疫组织化学方法对脊髓组织进行研究。NT-3和BDNF通过基因激活的脂肪移植物在体外和体内产生至少21天。在第7天和第21天，脂肪组织移植物在植入部位保持稳定。无论是bdnf激活的还是nt -3激活的脂肪移植对神经元变性都没有可检测到的限制作用。BDNF将小胶质细胞招募到病灶周围部位并减轻其炎症反应。基因激活的同质脂肪组织作为一种三维生物材料，在很长一段时间内将治疗分子输送到脊髓损伤部位。bdnf脂肪移植可减轻炎症反应。这些发现是否转化为功能恢复将需要延长观察时间。
Spinal cord injury (SCI) is a complex disease requiring a concerted multi-target approach. The most appropriate combination of therapeutic gene, cellular vehicle, and space filling scaffold still has to be determined. We present an approach that employs syngeneic adipose tissue serving as a three-dimensional biological implant, source of progenitor cells, and delivery system for therapeutic genes. In this pilot experiment, we evaluated the feasibility and short-term effects using gene-activated autologous fat grafts after SCI.An experimental SCI model was established in syngeneic Fischer 344 rats by a T9-T10 hemimyelonectomy. Fat tissue was harvested from two donor rats. Animals were divided into four groups and treated with either (i) fat grafts activated by an adenoviral vector carrying the human NT-3 cDNA, (ii) or BDNF, (iii) or with untreated fat grafts or (iv) remained untreated. Animals were euthanized either 7 or 21 days after surgery, and spinal cord tissue was investigated by histological and immunohistochemical methods.NT-3 and BDNF were produced by gene-activated fat grafts for at least 21 days in vitro and in vivo. Fat tissue grafts remained stable at the site of implantation at 7 days and at 21 days. Neither BDNF-activated nor NT-3-activated fat graft had a detectable limiting effect on the neuronal degeneration. BDNF recruited microglia to perilesional site and attenuated their inflammatory response.Gene-activated syngeneic fat tissue serves as a three-dimensional biological material delivering therapeutic molecules to the site of SCI over an extended period of time. The BDNF-fat graft attenuated the inflammatory response. Whether these findings translate into functional recovery will require extended observation times.