Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human

被引:10
作者
Deng, Hongping [1 ]
Zhang, Alexander [1 ]
Pang, Dillon Ren Rong [1 ,9 ]
Xi, Yinsheng [2 ]
Yang, Zhihong [1 ]
Matheson, Rudy [1 ]
Li, Guoping [3 ]
Luo, Hao [1 ,10 ]
Lee, Kang M. [1 ]
Fu, Qiang [1 ]
Zou, Zhongliang [1 ]
Chen, Tao [1 ]
Wang, Zhenjuan [1 ]
Rosales, Ivy A. [1 ]
Peters, Cole W. [1 ]
Yang, Jibing [4 ]
Coronel, Maria M. [5 ,6 ]
Yolcu, Esma S. [7 ,8 ]
Shirwan, Haval [7 ,8 ]
Garcia, Andres J. [5 ,6 ]
Markmann, James F. [1 ]
Lei, Ji [1 ]
机构
[1] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA
[2] Southern Med Univ, Sch Clin Med, Foshan 528300, Peoples R China
[3] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA
[5] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA
[6] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA
[7] Univ Missouri, Sch Med, Dept Child Hlth, Columbia, MO USA
[8] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO USA
[9] Univ Calif San Diego, Sch Biol Sci, San Diego, CA 92122 USA
[10] Gen Hosp Western Theater Command, Dept Gen Surg, Chengdu, Peoples R China
基金
美国国家卫生研究院;
关键词
BETA-CELLS; T-CELLS; B-CELLS; REVASCULARIZATION; IMMUNOSUPPRESSION; MODEL; POUCH;
D O I
10.1016/j.xcrm.2023.100959
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The transplanting islets to the liver approach suffers from an immediate posttransplant loss of islets of more than 50%, progressive graft dysfunction over time, and precludes recovery of grafts should there be serious complications such as the development of teratomas with grafts that are stem cell-derived islets (SC-islets). The omentum features an attractive extrahepatic alternative site for clinical islet transplantation. We explore an approach in which allogeneic islets are transplanted onto the omentum, which is bioengineered with a plasma-thrombin biodegradable matrix in three diabetic non-human primates (NHPs). Within 1 week post -transplant, each transplanted NHP achieves normoglycemia and insulin independence and remains stable until termination of the experiment. Success was achieved in each case with islets recovered from a single NHP donor. Histology demonstrates robust revascularization and reinnervation of the graft. This preclinical study can inform the development of strategies for b cell replacement including the use of SC-islets or other types of novel cells in clinical settings.
引用
收藏
页数:16
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