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The isolation and function of porcine islets from market weight pigs.
Cell Transplant. 2001; 10(3):235-46.CT

Abstract

The efficacy of clinical islet transplantation has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is confounded by the necessity of immunosuppression. the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. Porcine islet xenotransplantation, together with a successful immune intervention strategy, may provide the necessary clinical alternative. However, a major obstacle in evaluating this approach has been the difficulty of obtaining adequate volumes of functional islet tissue from pigs. Donors of market weight are preferable to retired breeders due to their abundance, lower animal and husbandry costs. and are more suitable to meet regulatory guidelines for donor tissue for xenotransplantation. We describe a simple isolation procedure that following purification yields a mean of 350,000 IE, corresponding to 179 units of insulin and 1.8 mg of DNA with an islet purity and viability in excess of 85% (n = 317 isolations). In both short- and long-term cell cultures, porcine islets demonstrated glucose-responsive insulin secretion. However, this secretion is density dependent, which may have significant consequences in the development of immunoisolation technologies to support porcine islet xenotransplantation. Following implantation into diabetic nude mice, porcine islets remained functional in excess of 1 year. Implantation of a bioartificial pancreas containing porcine islets into pancreatectomized dogs provided significant clinical benefit with an improved diabetic condition. Finally, secretagogue-induced insulin release was demonstrated in vitro from these devices after removal from immunocompetent recipients. Immunohistochemical staining identified well-granulated islets following long-term implantation in both the rodent and canine models. This study demonstrates the ability to isolate porcine islets in clinically relevant numbers from market animals, which survive and remain functional for prolonged periods of time in an immune-deficient or immunoprotected environment.

Authors+Show Affiliations

Circe Biomedical Inc, Lexington, MA 02421, USA. jack.oneil@joslin.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11437069

Citation

O'Neil, J J., et al. "The Isolation and Function of Porcine Islets From Market Weight Pigs." Cell Transplantation, vol. 10, no. 3, 2001, pp. 235-46.
O'Neil JJ, Stegemann JP, Nicholson DT, et al. The isolation and function of porcine islets from market weight pigs. Cell Transplant. 2001;10(3):235-46.
O'Neil, J. J., Stegemann, J. P., Nicholson, D. T., Gagnon, K. A., Solomon, B. A., & Mullon, C. J. (2001). The isolation and function of porcine islets from market weight pigs. Cell Transplantation, 10(3), 235-46.
O'Neil JJ, et al. The Isolation and Function of Porcine Islets From Market Weight Pigs. Cell Transplant. 2001;10(3):235-46. PubMed PMID: 11437069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The isolation and function of porcine islets from market weight pigs. AU - O'Neil,J J, AU - Stegemann,J P, AU - Nicholson,D T, AU - Gagnon,K A, AU - Solomon,B A, AU - Mullon,C J, PY - 2001/7/5/pubmed PY - 2002/1/5/medline PY - 2001/7/5/entrez SP - 235 EP - 46 JF - Cell transplantation JO - Cell Transplant VL - 10 IS - 3 N2 - The efficacy of clinical islet transplantation has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is confounded by the necessity of immunosuppression. the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. Porcine islet xenotransplantation, together with a successful immune intervention strategy, may provide the necessary clinical alternative. However, a major obstacle in evaluating this approach has been the difficulty of obtaining adequate volumes of functional islet tissue from pigs. Donors of market weight are preferable to retired breeders due to their abundance, lower animal and husbandry costs. and are more suitable to meet regulatory guidelines for donor tissue for xenotransplantation. We describe a simple isolation procedure that following purification yields a mean of 350,000 IE, corresponding to 179 units of insulin and 1.8 mg of DNA with an islet purity and viability in excess of 85% (n = 317 isolations). In both short- and long-term cell cultures, porcine islets demonstrated glucose-responsive insulin secretion. However, this secretion is density dependent, which may have significant consequences in the development of immunoisolation technologies to support porcine islet xenotransplantation. Following implantation into diabetic nude mice, porcine islets remained functional in excess of 1 year. Implantation of a bioartificial pancreas containing porcine islets into pancreatectomized dogs provided significant clinical benefit with an improved diabetic condition. Finally, secretagogue-induced insulin release was demonstrated in vitro from these devices after removal from immunocompetent recipients. Immunohistochemical staining identified well-granulated islets following long-term implantation in both the rodent and canine models. This study demonstrates the ability to isolate porcine islets in clinically relevant numbers from market animals, which survive and remain functional for prolonged periods of time in an immune-deficient or immunoprotected environment. SN - 0963-6897 UR - https://www.unboundmedicine.com/medline/citation/11437069/The_isolation_and_function_of_porcine_islets_from_market_weight_pigs_ L2 - https://journals.sagepub.com/doi/10.3727/000000001783986792?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -