Experimental study on peripheral nerve xenograft by induction of immuno-tolerance

诱导免疫耐受的周围神经异种移植实验研究

• 批准号: 12470377
• 负责人: NAKATSUKA Takashi
• 金额: $ 3.07万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470377/
• 关键词: peripheral nerve; xenograft; anti-CD4; CTLA4Ig; microsurgery; axon; regeneration; immunosuppression; 免疫抑制; 再生; 軸索

Anti-CD4 treatment has been shown to prolong survival of skin allografts as well as cardiac allografts. Anti-CD4 and anti-CD8 monoclonal antibodies prolonged concordant rat-to-mouse cardiac xenograft survival The fusion protein, CTLA4Ig, blocks T-cell-dependent antibody production and inhibits the proliferation of activated T cells restimulated with allogeneic cell linesWe transplanted Lewis rat sural nerve of 10mm length to the defect of mouse (BALB/c) sciatic nerve of 3mm using microsurgical technique under operating microscope. The experimental animals were divided into the following three groups : Group 1 (control) ; no treatment, Group 2 ; anti-CD4 (125/μg mouse) was given intraperitoneally on 2 days and immediately before transplantaticn, Group a CTLA4Ig (25μg/mouse) was given intraperitoneally just after transplantaticn and on 1 day and 3 days after transplantation. We examined the motor function recovery by Waking tract analysis and the specimen of the grafted nerve was taken at 8 weeks after transplantation for histological examinationThe walking tract test showed no evident differences in recovery of hindlimb motor function for 8 weeks after transplantation between three groups. The histological examination revealed the following results : In Group 1, there was remarkable formation of collagen fibers and the regenerated myelinated axons were only scattered in the xenograft and the diameter of the axon was small and the myelin sheath was thin. In Group 2, 3, on the contrary, many myelinated axons were observed diffusely in the grafted nerve. And the diameter of the regenerated axons was larger and the myelin sheath was thicker than Group 1From this study we conclude that short-term and small amount of administration of anti-CD4 or CTLA4Ig enables the axonal regeneration through peripheral nerve xenograft between rat and mouse

抗CD 4治疗已显示出延长皮肤同种异体移植物以及心脏同种异体移植物的存活。抗CD 4和抗CD 8单克隆抗体延长大鼠-小鼠异种心脏移植物的存活时间CTLA 4 Ig融合蛋白阻断T细胞依赖性抗体的产生，抑制同种异体细胞系再刺激的活化T细胞的增殖我们采用手术显微镜下显微外科技术，将长10 mm的刘易斯大鼠腓肠神经移植到3 mm的BALB/c小鼠坐骨神经缺损处。实验动物分为3组：1组（对照组）; 2组（未处理组）;抗CD 4抗体（125 μg/只）于移植前2天及移植前即刻腹腔注射; 113采用步行道分析法检测移植神经的运动功能恢复情况，并于移植后8周取移植神经标本进行组织学检查，步行道试验结果显示，移植后8周，三组间后肢运动功能恢复情况无明显差异。组织学检查结果显示：第1组移植物内胶原纤维形成明显，再生的有髓轴突散在分布，轴突直径小，髓鞘薄。2、3组则相反，在移植神经内可见大量弥漫性有髓轴突。结论：短期、少量应用抗CD_4或CTLA_（4 Ig）可促进大鼠和小鼠异种神经移植物的轴突再生

项目成果

Masahiro Nakagawa: "Schwann cell myelination occurred without basal lamina formation in laminin α2 chain-null mutant mice"Glia. 35. 101-110 (2001)

Masahiro Nakakawa：“在层粘连蛋白 α2 链无效突变小鼠中，雪旺细胞髓鞘形成没有形成基底层”Glia。 35. 101-110 (2001)

Kimata Y: "Comparison of innervated and noninnervated free flaps in oral reconstruction"Plast Reconstr Surg,. 104・5. 1307-1313 (1999)

Kimata Y：“口腔重建中受神经支配和无神经支配的游离皮瓣的比较”Plast Reconstr Surg，1307-1313（1999）。

木股敬裕: "口腔内再建における知覚皮弁の価値"形成外科. 43・3. 265-271 (2000)

Takahiro Kimata：“口腔内重建中的感觉皮瓣的价值”整形外科43・3。

Kawasaki Y: "Identification of myelinated motor and sensory axons in a regenerating mixed nerve"J Hand Surg. 25・1. 104-111 (2000)

川崎 Y：“再生混合神经中的有髓运动轴突和感觉轴突的识别”J Hand Surg. 25・1（2000）。

木股 敬裕: "口腔内再建における知覚皮弁の価値"形成外科. 43. 265-271 (2000)

Takahiro Kimata：“感觉皮瓣在口内重建中的价值”整形外科杂志 43. 265-271 (2000)。