Wang Wenjing, Gu Yuanjun, Tabata Yasuhiko, Miyamoto Masaaki, Hori Hiroshi, Nagata Natsuki, Touma Maki, Balamurugan A N, Kawakami Yoshiyuki, Nozawa Masumi, Inoue Kazutomo
Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawara-cho, Sakyo-ku, Kyoto, Japan.
Transplantation. 2002 Jan 15;73(1):122-9. doi: 10.1097/00007890-200201150-00023.
The subcutaneous site has been regarded as a potential site for a bioartificial pancreas. Transplantation of islets, encapsulated by the development of diverse biocompatible materials and structural designs, can reverse hyperglycemia in diabetic recipients.
Approximately 750 Sprague-Dawley rat islets macroencapsulated in an agarose/poly (styrene sulfonic acid) mixed gel were implanted into a prevascularized subcutaneous site. The site was constructed by subcutaneous injection of basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres in streptozotocin-induced C57BL/6 diabetic mice. Diabetic mice treated with bFGF-free gelatin microspheres and diabetic mice without any treatment undergoing the same subcutaneous transplantation were used as controls. After transplantation, non-fasting blood glucose, body weight, intraperitoneal glucose tolerance test, and histologic evaluations were processed.
All the recipients undergoing the subcutaneous xenograft returned to normoglycemia within 1 week after transplantation. Eight of 10 recipients in the bFGF+ group maintained normoglycemia for a period of 38-101 days and gradually gained increase of body weight. Two of 10 recipients became hyperglycemic again when the grafts were respectively retrieved at days 31 and 63. Intraperitoneal glucose tolerance tests at month 1 and 2 revealed significant ameliorated glucose tolerance but a tendency to reduced glucose tolerance when compared respectively with those of the streptozotocin-induced diabetic mice and normal mice. Histologic examination revealed that islets within the retrieved grafts at days 31 and 63 were viable and intact; no fibrotic overgrowth was present around the surface of grafts.
A successfully prevascularized subcutaneous site could be constructed by a tissue bioengineering approach. Xenotransplantation of the agarose/poly (styrene sulfonic acid) mixed gel-based bioartificial pancreas in the prevascularized subcutaneous site could reverse diabetes in mice.
皮下部位被认为是生物人工胰腺的潜在植入部位。通过多种生物相容性材料和结构设计包裹的胰岛移植，可使糖尿病受体的高血糖症得到逆转。
将约750个包裹于琼脂糖/聚（苯乙烯磺酸）混合凝胶中的斯普拉格-道利大鼠胰岛植入预先血管化的皮下部位。该部位通过在链脲佐菌素诱导的C57BL/6糖尿病小鼠皮下注射含碱性成纤维细胞生长因子（bFGF）的明胶微球构建而成。将接受不含bFGF的明胶微球治疗的糖尿病小鼠和未接受任何治疗但进行相同皮下移植的糖尿病小鼠作为对照。移植后，进行非空腹血糖检测、体重测量、腹腔葡萄糖耐量试验以及组织学评估。
所有接受皮下异种移植的受体在移植后1周内恢复正常血糖水平。bFGF+组的10只受体中有8只维持正常血糖水平38 - 101天，并逐渐体重增加。10只受体中有2只在移植后第31天和第63天分别取出移植物时再次出现高血糖。第1个月和第2个月的腹腔葡萄糖耐量试验显示，与链脲佐菌素诱导的糖尿病小鼠相比，葡萄糖耐量有显著改善，但与正常小鼠相比有葡萄糖耐量降低的趋势。组织学检查显示，在第31天和第63天取出的移植物中的胰岛存活且完整；移植物表面周围未出现纤维化过度生长。
通过组织生物工程方法可成功构建预先血管化的皮下部位。在预先血管化的皮下部位进行基于琼脂糖/聚（苯乙烯磺酸）混合凝胶的生物人工胰腺异种移植可逆转小鼠的糖尿病。
