Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.
Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
Gozde
G
Uzunalli
Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
Yasin
Y
Tumtas
Pancreas Islet Cell Research Center, Ankara Diskapi Yildirim Beyazit Training and Research Hospital Etlik Polyclinic, Department of Endocrinology and Metabolism, Ankara 06800, Turkey; Hacettepe University, School of Medicine, Department of Endocrinology, Ankara 06100, Turkey. Electronic address: delibasi@hacettepe.edu.tr.
Tuncay
T
Delibasi
Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
Oncay
O
Yasa
Pancreas Islet Cell Research Center, Ankara Diskapi Yildirim Beyazit Training and Research Hospital Etlik Polyclinic, Department of Endocrinology and Metabolism, Ankara 06800, Turkey; Gazi University, Faculty of Science, Department of Chemistry, Ankara 06560, Turkey.
Sercan
S
Mercan
Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey. Electronic address: moguler@unam.bilkent.edu.tr.
Mustafa O
MO
Guler
Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey. Electronic address: atekinay@bilkent.edu.tr.
Ayse B
AB
Tekinay
D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D005782:Gels / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D057139:Nanofibers / Q000737:chemistry*; D009852:Omentum / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar
D001786:Blood Glucose; D005782:Gels; D010455:Peptides; D006493:Heparin
Angiogenesis; Heparin; Islet transplantation; Peptide nanofibers; Self-assembly