TY - JOUR
T1 - Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats
AU - Paez-Mayorga, Jesus
AU - Campa-Carranza, Jocelyn Nikita
AU - Capuani, Simone
AU - Hernandez, Nathanael
AU - Liu, Hsuan-Chen
AU - Chua, Corrine Ying Xuan
AU - Pons-Faudoa, Fernanda Paola
AU - Malgir, Gulsah
AU - Alvarez, Bella
AU - Niles, Jean A
AU - Argueta, Lissenya B
AU - Shelton, Kathryn A
AU - Kezar, Sarah
AU - Nehete, Pramod N
AU - Berman, Dora M
AU - Willman, Melissa A
AU - Li, Xian C
AU - Ricordi, Camillo
AU - Nichols, Joan E
AU - Gaber, A Osama
AU - Kenyon, Norma S
AU - Grattoni, Alessandro
N1 - Funding Information:
The authors are grateful to Dr. Marco Farina for insightful discussion and information. The authors thank Dr. Jianhua (James) Gu from the electron microscopy core of Houston Methodist Research Institute; Dr. Andreana L. Rivera, Yuelan Ren, and Sandra Steptoe from the research pathology core of Houston Methodist Research Institute; Drs. Yitian Xu, Licheng Zhang, and Shu-Hsia Chen from the ImmunoMonitoring Core of Houston Methodist Research Institute; Dr. David L. Haviland and Nicole Vaughn from the flow cytometry core of Houston Methodist Research Institute; Alex Rabassa and Waldo L. Diaz from the Diabetes Research Institute at the University of Miami for pancreas procurement and islet isolation; and Luke Segura, Elizabeth Lindemann, Dana Salazar, Bharti Nehete, and Dr. Greg Wilkerson from the Michale E. Keeling Center for Comparative Medicine and Research at UTMDACC for support in NHP studies. Figure was partially created with biorender.org. The authors also thank graphic designer Virginia Facciotto ([email protected]) for the preparation of schematics and illustrations. Funding support from Juvenile Diabetes Research Foundation 1-INO-2018-595-A-N (A.G.), Vivian L. Smith Foundation (A.G.), Houston Methodist Research Institute (A.G.), Diabetes Research Institute (N.K.), and in part by NIH NIDDK R01DK132104 (A.G., J.N.).
Funding Information:
The authors are grateful to Dr. Marco Farina for insightful discussion and information. The authors thank Dr. Jianhua (James) Gu from the electron microscopy core of Houston Methodist Research Institute; Dr. Andreana L. Rivera, Yuelan Ren, and Sandra Steptoe from the research pathology core of Houston Methodist Research Institute; Drs. Yitian Xu, Licheng Zhang, and Shu-Hsia Chen from the ImmunoMonitoring Core of Houston Methodist Research Institute; Dr. David L. Haviland and Nicole Vaughn from the flow cytometry core of Houston Methodist Research Institute; Alex Rabassa and Waldo L. Diaz from the Diabetes Research Institute at the University of Miami for pancreas procurement and islet isolation; and Luke Segura, Elizabeth Lindemann, Dana Salazar, Bharti Nehete, and Dr. Greg Wilkerson from the Michale E. Keeling Center for Comparative Medicine and Research at UTMDACC for support in NHP studies. Figure 3a was partially created with biorender.org. The authors also thank graphic designer Virginia Facciotto ([email protected]) for the preparation of schematics and illustrations. Funding support from Juvenile Diabetes Research Foundation 1-INO-2018-595-A-N (A.G.), Vivian L. Smith Foundation (A.G.), Houston Methodist Research Institute (A.G.), Diabetes Research Institute (N.K.), and in part by NIH NIDDK R01DK132104 (A.G., J.N.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12/26
Y1 - 2022/12/26
N2 - Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management.
AB - Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management.
KW - Rats
KW - Animals
KW - Male
KW - Diabetes Mellitus, Type 1/therapy
KW - Immunosuppression Therapy
KW - Islets of Langerhans Transplantation
KW - Immune Tolerance
KW - Immunosuppressive Agents/pharmacology
KW - Islets of Langerhans
KW - Graft Survival
UR - http://www.scopus.com/inward/record.url?scp=85144637828&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144637828&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-35629-z
DO - 10.1038/s41467-022-35629-z
M3 - Article
C2 - 36572684
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7951
ER -