2022-05-13 ジョージア工科大学
しかし、ジョージア工科大学のAndrés García研究員が率いる研究チームは、これまでの小動物実験においてこのハードルを克服した。この技術では、マイクロゲルと呼ばれる合成ハイドロゲル粒子を用いる。このマイクロゲルは、SA-FasLと呼ばれる強力な免疫調節タンパク質を提示し、身体の免疫反応を調節することで、移植されたインスリン産生細胞が安全にその役割を果たし、血糖値を調節し、糖尿病と闘えるようにする。
Science Advances誌に掲載されたGarcíaと共同研究者の新しい研究は、この希望に満ちた治療戦略を臨床に近づけるものである。
<関連情報>
- https://research.gatech.edu/biomaterial-improves-islet-transplants-treatment-type-1-diabetes
- https://www.science.org/doi/10.1126/sciadv.abm9881
FasLマイクロゲルは霊長類における膵島移植片の免疫受容を誘発する FasL microgels induce immune acceptance of islet allografts in nonhuman primates
JI LEI,MARÍA M. CORONEL,ESMA S. YOLCU,HONGPING DENG,ORLANDO GRIMANY-NUNO,MICHAEL D. HUNCKLER,VAHAP ULKER ,ZHIHONG YANG,KANG M. LEE,ALEXANDER ZHANG ,HAO LUO,COLE W. PETERS,ZHONGLIANG ZOU,TAO CHEN,ZHENJUAN WANG,COLLEEN S. MCCOY ,IVY A. ROSALES ,JAMES F. MARKMANN,HAVAL SHIRWAN AND ANDRÉS J. GARCÍA
Science Advances Published:13 May 2022
DOI: 10.1126/sciadv.abm9881
Abstract
Islet transplantation to treat insulin-dependent diabetes is greatly limited by the need for maintenance immunosuppression. We report a strategy through which cotransplantation of allogeneic islets and streptavidin (SA)–FasL–presenting microgels to the omentum under transient rapamycin monotherapy resulted in robust glycemic control, sustained C-peptide levels, and graft survival in diabetic nonhuman primates for >6 months. Surgical extraction of the graft resulted in prompt hyperglycemia. In contrast, animals receiving microgels without SA-FasL under the same rapamycin regimen rejected islet grafts acutely. Graft survival was associated with increased number of FoxP3+ cells in the graft site with no significant changes in T cell systemic frequencies or responses to donor and third-party antigens, indicating localized tolerance. Recipients of SA-FasL microgels exhibited normal liver and kidney metabolic function, demonstrating safety. This localized immunomodulatory strategy succeeded with unmodified islets and does not require long-term immunosuppression, showing translational potential in β cell replacement for treating type 1 diabetes.
