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Neonatal pig islets

H Eguchi, T Kawamura, N Kashiyama, R Matsuura, R Sakai, K Nakahata, P-C Lo, M Asada, A Maeda, M Goto, M Toyoda, H Okuyama, S Miyagawa
The pig pancreas is considered to be one of the most suitable sources of islets for clinical xenotransplantation. However, after producing α1-3galactosyltransferase knockout pigs, most of the organs of these pigs showed less antigenicity to the human body. Wild-type adult pig islets (APIs) that originally produced negligible levels of α-Gal, different from neonatal porcine islet-like cell clusters, showed a clear antigenicity to human serum. Concerning the so-called non-Gal epitopes, many studies related to glycoproteins and glycolipids are ongoing in efforts to identify them...
May 2016: Transplantation Proceedings
Kandis Wright, Rachel Dziuk, Payal Mital, Gurvinder Kaur, Jannette M Dufour
Xenotransplantation has vast clinical potential but is limited by the potent immune responses generated against xenogeneic tissue. Immune-privileged Sertoli cells (SC) survive xenotransplantation long-term (>90 days) without immunosuppression, making SC an ideal model to identify xenograft survival mechanisms. Xenograft rejection includes the binding of natural and induced antibodies, and activation of complement cascade. Using an in vitro cytotoxicity assay, where cells were cultured with human serum and complement, we demonstrated neonatal pig SC (NPSC) are resistant to complement mediated cell lysis and express complement inhibitory factors, membrane cofactor protein (MCP; CD46) and decay accelerating factor (DAF; CD55) at significantly higher levels than neonatal pig islets (NPI), non-immune privileged controls...
June 14, 2016: Cell Transplantation
Lelia Wolf-van Buerck, Marion Schuster, Andrea Baehr, Tanja Mayr, Sonja Guethoff, Jan Abicht, Bruno Reichart, Yun-Chung Nam-Apostolopoulos, Nikolai Klymiuk, Eckhard Wolf, Jochen Seissler
BACKGROUND: Intraportal infusion is currently the method of choice for clinical islet cell transplantation but suffers from poor efficacy. As the liver may not represent an optimal transplantation site for Langerhans islets, we examined the potential of neonatal porcine islet-like clusters (NPICCs) to engraft in skeletal muscle as an alternative transplantation site. METHODS: Neonatal porcine islet-like clusters were isolated from 2- to 5-day-old piglets and either transplanted under the kidney capsule (s...
November 2015: Xenotransplantation
Rahul Krishnan, Nhat Truong, Marina Gerges, Miranda Stiewig, Nicholas Neel, KhueTu Ho-Nguyen, Christina Kummerfeld, Michael Alexander, Tom Spizzo, Michael Martin, Clarence E Foster, Edwin S Monuki, Jonathan R T Lakey
BACKGROUND: During the process of islet isolation, pancreatic enzymes are activated and released, adversely affecting islet survival and function. We hypothesize that the exocrine component of pancreases harvested from pre-weaned juvenile pigs is immature and hence pancreatic tissue from these donors is protected from injury during isolation and prolonged tissue culture. METHODS: Biopsy specimens taken from pancreases harvested from neonatal (5-10 days), pre-weaned juvenile (18-22 days), weaned juvenile (45-60 days), and young adult pigs (>90 days) were fixed and stained with hematoxylin and eosin...
September 2015: Xenotransplantation
Santosh Nagaraju, Suzanne Bertera, Takayuki Tanaka, Hidetaka Hara, Gina R Rayat, Martin Wijkstrom, David Ayares, Massimo Trucco, David K C Cooper, Rita Bottino
BACKGROUND: Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR). METHODS: Neonatal isletlike cell clusters were harvested from three groups of piglets-(i) wild-type (genetically unmodified), (ii) α1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39...
July 2015: Xenotransplantation
B M Martin, K P Samy, M C Lowe, P W Thompson, J Cano, A B Farris, M Song, C R Dove, F V Leopardi, E A Strobert, J B Jenkins, B H Collins, C P Larsen, A D Kirk
Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood-mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations...
May 2015: American Journal of Transplantation
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