Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Diabetologia. 2010 May;53(5):937-945. doi: 10.1007/s00125-009-1653-8. Epub 2010 Jan 26.
AIMS/HYPOTHESIS: Islet transplantation is a promising treatment for type 1 diabetes but is hampered by a shortage of donor human tissue and early failure. Research on islet cell transplantation includes finding new sources of cells and immunoisolation to protect from immune assault and tumourigenic potential. Small islet cell aggregates were studied to determine if their survival and function were superior to intact islets within microcapsules because of reduced oxygen transport limitation and inflammatory mediators.
Islet cell aggregates were generated by dispersing rat islets into single cells and allowing them to re-aggregate in culture. Rat islets and islet cell aggregates were encapsulated in barium alginate capsules and studied when cultured in low (0.5% or 2%) or normal (20%) oxygen, or transplanted into mice.
Encapsulated islet cell aggregates were able to survive and function better than intact islets in terms of oxygen-consumption rate, nuclei counts, insulin-to-DNA ratio and glucose-stimulated insulin secretion. They also had reduced expression of pro-inflammatory genes. Islet cell aggregates showed reduced tissue necrosis in an immunodeficient transplant model and a much greater proportion of diabetic xenogeneic transplant recipients receiving islet cell aggregates (tissue volume of only 85 islet equivalents) had reversal of hyperglycaemia than recipients receiving intact islets.
CONCLUSIONS/INTERPRETATION: These aggregates were superior to intact islets in terms of survival and function in low-oxygen culture and during transplantation and are likely to provide more efficient utilisation of islet tissue, a finding of importance for the future of cell therapy for diabetes.
目的/假设：胰岛移植是治疗 1 型糖尿病的一种有前途的方法，但由于供体人类组织的短缺和早期失败而受到阻碍。胰岛细胞移植的研究包括寻找新的细胞来源和免疫隔离，以防止免疫攻击和致瘤潜能。研究了胰岛细胞聚集体，以确定它们的存活和功能是否优于微胶囊内完整的胰岛，因为它们的氧传输限制和炎症介质减少。
通过将大鼠胰岛分散成单个细胞并在培养中重新聚集，生成胰岛细胞聚集体。将大鼠胰岛和胰岛细胞聚集体包裹在钡藻酸盐胶囊中，并在低氧（0.5%或 2%）或正常氧（20%）条件下培养或移植到小鼠中进行研究。
与完整的胰岛相比，包裹的胰岛细胞聚集体在氧消耗率、核计数、胰岛素与 DNA 比值和葡萄糖刺激的胰岛素分泌方面具有更好的存活和功能。它们还具有较低的促炎基因表达。胰岛细胞聚集体在免疫缺陷移植模型中显示出减少的组织坏死，并且在接受胰岛细胞聚集体（仅 85 个胰岛当量的组织体积）的糖尿病异种移植受者中，逆转高血糖的比例明显高于接受完整胰岛的受者。
结论/解释：这些聚集体在低氧培养和移植过程中在存活和功能方面优于完整的胰岛，并且可能更有效地利用胰岛组织，这对未来的糖尿病细胞治疗具有重要意义。
