Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration

被引:103
作者
Wakao, Shohei
Hayashi, Takuya [2 ]
Kitada, Masaaki
Kohama, Misaki
Matsue, Dai
Teramoto, Noboru [2 ]
Ose, Takayuki [2 ]
Itokazu, Yutaka [3 ]
Koshino, Kazuhiro [2 ]
Watabe, Hiroshi [2 ]
Iida, Hidehiro [2 ]
Takamoto, Tomoaki [4 ]
Tabata, Yasuhiko [4 ]
Dezawa, Mari [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Dept Stem Cell Biol & Histol, Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Natl Cardiovasc Ctr, Res Inst, Adv Med Engn Ctr, Dept Invest Radiol, Osaka 5658565, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Anat & Neurobiol, Kyoto 6068501, Japan
[4] Kyoto Univ, Inst Frontier Med Sci, Field Tissue Engn, Dept Biomat, Kyoto 6068507, Japan
关键词
Mesenchymal stem cells; Monkey; Schwann cells; Nerve regeneration; Peripheral nerve; Transdifferentiation; RAT SPINAL-CORD; OLFACTORY ENSHEATHING GLIA; IN-VITRO; STEM-CELLS; AXONAL REGENERATION; FUNCTIONAL RECOVERY; DIFFERENTIATION; MODEL; GRAFT; STRATEGIES;
D O I
10.1016/j.expneurol.2010.01.022
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Based on their differentiation ability, bone marrow stromal cells (MSCs) are a good source for cell therapy. Using a cynomolgus monkey peripheral nervous system injury model, we examined the safety and efficacy of Schwann cells induced from MSCs as a source for auto-cell transplantation therapy in nerve injury. Serial treatment of monkey MSCs with reducing agents and cytokines induced their differentiation into cells with Schwann cell properties at a very high ratio. Expression of Schwann cell markers was confirmed by both immunocytochemistry and reverse transcription-polymerase chain reaction. Induced Schwann cells were used for auto-cell transplantation into the median nerve and followed-up for 1 year. No abnormalities were observed in general conditions. Ki67-immunostaining revealed no sign of massive proliferation inside the grafted tube. Furthermore, (18)F-fluorodeoxygluocose-positron emission tomography scanning demonstrated no abnormal accumulation of radioactivity except in regions with expected physiologic accumulation. Restoration of the transplanted nerve was corroborated by behavior analysis, electrophysiology and histological evaluation. Our results suggest that auto-cell transplantation therapy using MSC-derived Schwann cells is safe and effective for accelerating the regeneration of transected axons and for functional recovery of injured nerves. The practical advantages of MSCs are expected to make this system applicable for spinal cord injury and other neurotrauma or myelin disorders where the acceleration of regeneration is expected to enhance functional recovery. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:537 / 547
页数:11
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