Interim report on the effective intraperitoneal therapy of insulin-dependent diabetes mellitus in pet dogs using “Neo-Islets,” aggregates of adipose stem and pancreatic islet cells (INAD 012-776)

English version

Autoři: Anna Gooch ^aff001; Ping Zhang ^aff001; Zhuma Hu ^aff001; Natasha Loy Son ^aff002; Nicole Avila ^aff002; Julie Fischer ^aff002; Gregory Roberts ^aff003; Rance Sellon ^aff003; Christof Westenfelder ^aff001
Působiště autorů: SymbioCellTech, LLC, Salt Lake City, Utah, United States of America ^aff001; Veterinary Specialty Hospital, San Diego, California, United States of America ^aff002; Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington, United States of America ^aff003; Department of Medicine, Division of Nephrology, University of Utah, Salt Lake City, Utah, United States of America ^aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0218688

Souhrn

We previously reported that allogeneic, intraperitoneally administered “Neo-Islets,” composed of cultured pancreatic islet cells co-aggregated with high numbers of immunoprotective and cytoprotective Adipose-derived Stem Cells, reestablished, through omental engraftment, redifferentiation and splenic and omental up-regulation of regulatory T-cells, normoglycemia in autoimmune Type-1 Diabetic Non-Obese Diabetic (NOD) mice without the use of immunosuppressive agents or encapsulation devices. Based on these observations, we are currently testing this Neo-Islet technology in an FDA guided pilot study (INAD 012–776) in insulin-dependent, spontaneously diabetic pet dogs by ultrasound-guided, intraperitoneal administration of 2x10e5 Neo-Islets/kilogram body weight to metabolically controlled (blood glucose, triglycerides, thyroid and adrenal functions) and sedated animals. We report here interim observations on the first 4 canine Neo-Islet-treated, insulin-dependent pet dogs that are now in the early to intermediate-term follow-up phase of the planned 3 year study (> 6 months post treatment). Current results from this translational study indicate that in dogs, Neo-Islets appear to engraft, redifferentiate and physiologically produce insulin, and are rejected by neither auto- nor allo-immune responses, as evidenced by (a) an absent IgG response to the allogeneic cells contained in the administered Neo-Islets, and (b) progressively improved glycemic control that achieves up to a 50% reduction in daily insulin needs paralleled by a statistically significant decrease in serum glucose concentrations. This is accomplished without the use of anti-rejection drugs or encapsulation devices. No adverse or serious adverse events related to the Neo-Islet administration have been observed to date. We conclude that this minimally invasive therapy has significant translational relevance to veterinary and clinical Type 1 diabetes mellitus by achieving complete and at this point partial glycemic control in two species, i.e., diabetic mice and dogs, respectively.

Klíčová slova:

Biology and life sciences – Organisms – Eukaryota – Animals – Vertebrates – Amniotes – Mammals – Dogs – Animal types – Pets and companion animals – Biochemistry – Hormones – Anatomy – Body fluids – Blood – Physiology – Zoology – Genetics – Gene expression – Medicine and health sciences – Endocrinology – Diabetic endocrinology – Insulin – Endocrine disorders – Metabolic disorders – Blood sugar – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Carbohydrates – Monosaccharides – Glucose – Organic chemistry – Research and analysis methods – Immunologic techniques – Immunoassays – Enzyme-linked immunoassays

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Interim report on the effective intraperitoneal therapy of insulin-dependent diabetes mellitus in pet dogs using “Neo-Islets,” aggregates of adipose stem and pancreatic islet cells (INAD 012-776)

Souhrn

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