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Biomaterials. 2018 Jul;171:164-177. doi: 10.1016/j.biomaterials.2018.04.028. Epub 2018 Apr 16.

Polymeric nano-shielded islets with heparin-polyethylene glycol in a non-human primate model.

Author information

1
Department of Surgery, VHS Medical Center, Seoul 05368, Republic of Korea.
2
Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
3
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
4
Transplantation Research Center, Samsung Biomedical Research Institute, Seoul 06351, Republic of Korea.
5
Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
6
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang-si, Republic of Korea.
7
Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: yrbyun@snu.ac.kr.
8
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Transplantation Research Center, Samsung Biomedical Research Institute, Seoul 06351, Republic of Korea. Electronic address: kmhyj111@gmail.com.

Abstract

Intraportal pancreatic islet transplantation incurs huge cell losses during its early stages due to instant blood-mediated inflammatory reactions (IBMIRs), which may also drive regulation of the adaptive immune system. Therefore, a method that evades IBMIR will improve clinical islet transplantation. We used a layer-by-layer approach to shield non-human primate (NHP) islets with polyethylene glycol (nano-shielded islets, NSIs) and polyethylene glycol plus heparin (heparin nano-shielded islets; HNSIs). Islets ranging from 10,000 to 20,000 IEQ/kg body weight were transplanted into 19 cynomolgus monkeys (n = 4, control; n = 5, NSI; and n = 10, HNSI). The mean C-peptide positive graft survival times were 68.5, 64 and 108 days for the control, NSI and HNSI groups, respectively (P = 0.012). HNSI also reduced the factors responsible for IBMIR in vitro. Based on these data, HNSIs in conjunction with clinically established immunosuppressive drug regimens will result in superior outcomes compared to those achieved with the current protocol for clinical islet transplantation.

KEYWORDS:

Cynomolgus monkey; Instant blood-mediated inflammatory reaction (IBMIRs); Islet transplantation; PEGylation

[Indexed for MEDLINE]

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