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Microfluidics-generated pancreatic islet microfibers for enhanced immunoprotection
Authors:Yesl Jun  Min Jun Kim  Yong Hwa Hwang  Eun Ae Jeon  Ah Ran Kang  Sang-Hoon Lee  Dong Yun Lee
Affiliation:1. Department of Biomedical Engineering, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea;2. Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea
Abstract:Pancreatic islet transplantation is a promising method for treatment of type 1 diabetes mellitus. However, transplanted islets can be destroyed due to host immune reactions. To immunologically protect transplanted islets, here an immunoprotective microfiber including islets by using a polydimethylsiloxane (PDMS)-based microfluidic device is newly designed. A cylindrical-flow channel in the microfluidic platform is used for producing collagen-alginate composite (CAC) fibers. This enables mass production and uniform diameter distribution (<250 μm) without protruding islets. Collagen, which is the main extracellular matrix component, is added to alginate to mimic the native islet microenvironment. Compared to free islets (control) and alginate-fiber-encapsulated islets, CAC-fiber-encapsulated islets show higher viability and normal insulin secretion. When CAC-fiber-encapsulated islets (1200 islet equivalent) are implanted into the intraperitoneal cavity of streptozotocin-induced diabetic BALB/C mice, the blood glucose levels of all mice return to normoglycemia. Moreover, intraperitoneal glucose tolerance tests demonstrate that islets in the CAC-fiber have similar glucose responsiveness to those of non-diabetic normal mice. These results are attributed to the immunoprotection of the transplanted islets from host immune reactions. On the other hand, all free islets are completely rejected within a week due to severe immune responses. Collectively, fabrication of CAC fibers using microfluidic devices can be used for successful islet transplantation.
Keywords:Collagen-Alginate composite (CAC)   Immunoprotection   Islet encapsulation   Microfluidics   Xenotransplantation
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