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Polymeric nano-shielded islets with heparin-polyethylene glycol in a non-human primate model
Park, Hyojun,Haque, Muhammad R.,Park, Jae Berm,Lee, Kyo Won,Lee, Sanghoon,Kwon, Yeongbeen,Lee, Han Sin,Kim, Geun-Soo,Shin, Du Yeon,Jin, Sang-Man,Kim, Jae Hyeon,Kang, Hee Jung,Byun, Youngro,Kim, Sung J Elsevier 2018 Biomaterials Vol.171 No.-
<P><B>Abstract</B></P> <P>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 (<I>P</I> = 0.012). HNSI also reduced the factors responsible for IBMIR <I>in vitro</I>. 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.</P>