A Bioartificial Pancreas with “Immune Stealth” and Continuous Oxygen Supply for Islet Transplantation
Yin Zheng
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
Search for more papers by this authorWenyi Yang
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
Search for more papers by this authorWeisong Gao
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
Search for more papers by this authorXinge Zhang
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorCorresponding Author
Zhongming Wu
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Mo Wang
Vascular Surgury, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorYin Zheng
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
Search for more papers by this authorWenyi Yang
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
Search for more papers by this authorWeisong Gao
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
Search for more papers by this authorXinge Zhang
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorCorresponding Author
Zhongming Wu
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021 China
Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Shandong Institute of Endocrine and Metabolic Diseases, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, Shandong, 250012 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Mo Wang
Vascular Surgury, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorDedicated to the 40th anniversary of the Institute of Polymer Chemistry at Nankai University
Abstract
Transplantation of microencapsulated islet cells remains a promising strategy for the normalization of glucose metabolism control in type 1 diabetes mellitus. However, vigorous host immunologic rejection, fibrotic overgrowth around the microcapsules, and poor oxygen supply often lead to graft failure. Herein, a bioartificial pancreas is constructed, which incorporates the “stealth effect” based on polyethylene glycol copolymers and the high oxygen-carrying performance of fluorinated nanoparticles. Polycationic poly(l-lysine)-grafted-poly(ethylene glycol) is successfully coated on the surface of alginate microcapsules through electrostatic interaction, which can not only resist fibrinogen adhesion and avoid excessive fibrosis around the microcapsules but also isolate the host immune system from attacking, achieving a “stealth effect” of microencapsulated islet cells. Furthermore, the coloading of fluoride-based O2 nanocarriers gives them enhanced oxygen-carrying and continuous oxygen supply capabilities, thereby effectively prolonging the survival of islet cells. The intracapsular islet cells still display similar cell viability and almost normal insulin secretion function even in long-term culture under hypoxic conditions. Collectively, here a new approach is opened for microencapsulated islets to efficiently evade host immune attack and improve oxygen supply and a promising strategy is provided for islet transplantation in type 1 diabetes mellitus.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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