Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells
Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells
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DOI：
10.1046/j.0953-816x.2001.01814.x
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发表时间：
2001-12-01
影响因子：
3.4
通讯作者：
Sawada, H
中科院分区：
文献类型：
--
作者：
Dezawa, M;Takahashi, I;Sawada, H
骨髓基质细胞（MSCs）是一种多能干细胞，具有分化为骨、软骨、脂肪和肌肉的潜能。我们现在证明，间充质干细胞可以被诱导分化成具有许旺细胞特征的细胞，能够引起周围神经系统再生的成年大鼠，间充质干细胞处理与β-巯基乙醇，然后视黄酸和培养中存在的毛喉素，碱性FGF，PDGF和heregulin，改变形态学成细胞类似原代培养的许旺细胞和表达p75，S-100，GFAP和O 4。MSC通过用编码绿色荧光蛋白（GFP）的逆转录病毒转导进行遗传工程化，然后通过用上述因子处理分化。它们被移植到坐骨神经的切断端，然后在手术后3周内神经纤维再生旺盛。用共聚焦显微镜和免疫电子显微镜观察到GFP表达的MSCs对再生纤维的髓鞘形成作用。结果表明，MSC能够分化为髓鞘形成细胞，能够支持神经纤维再生，因此它们可以用于诱导神经再生。
Bone marrow stromal cells (MSCs) are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. We now demonstrate that MSCs can be induced to differentiate into cells with Schwann cell characteristics, capable of eliciting peripheral nervous system regeneration in adult rats, MSCs treated with beta-mercaptoethanol followed by retinoic acid and cultured in the presence of forskolin, basic-FGF, PDGF and heregulin, changed morphologically into cells resembling primary cultured Schwann cells and expressing p75, S-100, GFAP and O4. The MSCs were genetically engineered by transduction with retrovirus encoding green fluorescent protein (GFP), and then differentiated by treatment with factors described above. They were transplanted into the cut ends of sciatic nerves, which then responded with vigorous nerve fibre regeneration within 3 weeks of the operation. Myelination of regenerated fibers by GFP-expressing MSCs was recognized using confocal and immunoelectron microscopy. The results suggest that MSCs are able to differentiate into myelinating cells, capable of supporting nerve fibre regrowth, and they can therefore be applied to induce nerve regeneration.