Olsson R, Carlsson P-O
Department of Medical Cell Biology, Uppsala University, Husargatan 3, Box 571, 751 23, Uppsala, Sweden.
Diabetologia. 2005 Mar;48(3):469-76. doi: 10.1007/s00125-004-1650-x. Epub 2005 Feb 5.
AIMS/HYPOTHESIS: Recent studies suggest that donor endothelial cells may contribute to islet graft revascularisation. Since islet endothelial cells disappear during culture, we hypothesised that transplantation of islets without prior culture is beneficial for their engraftment.
Cultured (4-7 days) or freshly isolated islets (<4 h after donor pancreas extirpation) were syngeneically transplanted into Wistar-Furth rats and C57Bl/6 mice beneath the renal capsule. Islet graft revascularisation was evaluated by measuring vascular density, blood flow and tissue oxygen tension. Islet graft function was investigated by a minimal islet mass model in inbred mice (C57Bl/6).
Four days after implantation, the partial pressure of oxygen (pO2) in the transplanted cultured islets was less than 10 mmHg (1.33 kPa), but tended to be higher in grafts composed of freshly isolated islets. The pO2 in the grafts of freshly isolated islets had more than doubled 4 weeks later, whereas the pO2 in the grafts of cultured islets remained at values similar to those recorded 4 days after transplantation. Transplanted freshly isolated islets also had a higher vascular density than transplanted cultured islets (approximately 40 vs approximately 25% of that in endogenous islets) when investigated 1 month post-implantation. When applying a minimal islet mass model in inbred mice, 200 freshly isolated islets cured alloxan-diabetic mice in all cases, whereas only 33% of the group receiving similar numbers of cultured islets were cured.
CONCLUSIONS/INTERPRETATION: Transplantation of pancreatic islets without prior culture is beneficial for their vascular engraftment and function.
目的/假设：近期研究表明，供体内皮细胞可能有助于胰岛移植后的血管重建。由于胰岛内皮细胞在培养过程中会消失，我们推测未经预先培养的胰岛移植对其植入有益。
将培养（4 - 7天）或刚分离的胰岛（供体胰腺切除后<4小时）同基因移植到Wistar - Furth大鼠和C57Bl/6小鼠的肾被膜下。通过测量血管密度、血流量和组织氧张力来评估胰岛移植后的血管重建情况。通过近交系小鼠（C57Bl/6）的最小胰岛量模型研究胰岛移植后的功能。
植入后4天，移植的培养胰岛中的氧分压（pO2）低于10 mmHg（1.33 kPa），但由刚分离的胰岛组成的移植物中的氧分压往往更高。4周后，刚分离的胰岛移植物中的pO2增加了一倍多，而培养胰岛移植物中的pO2仍保持在移植后4天记录的相似水平。植入1个月后研究发现，移植的刚分离的胰岛的血管密度也高于移植的培养胰岛（约为内源性胰岛血管密度的40%，而培养胰岛约为25%）。在近交系小鼠中应用最小胰岛量模型时，200个刚分离的胰岛在所有情况下都治愈了四氧嘧啶糖尿病小鼠，而接受相似数量培养胰岛的组中只有33%的小鼠被治愈。
结论/解读：未经预先培养的胰岛移植对其血管植入和功能有益。
