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1.
PLoS One ; 14(9): e0218688, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536503

RESUMO

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.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Diabetes Mellitus Tipo 1/veterinária , Doenças do Cão/terapia , Transplante das Ilhotas Pancreáticas , Animais , Biomarcadores , Glicemia , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Diabetes Mellitus Experimental , Doenças do Cão/imunologia , Doenças do Cão/metabolismo , Cães , Feminino , Perfilação da Expressão Gênica , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante das Ilhotas Pancreáticas/métodos , Isoanticorpos/imunologia , Masculino , Células-Tronco/citologia , Células-Tronco/metabolismo
2.
Vet Surg ; 45(S1): O77-O83, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27706826

RESUMO

OBJECTIVE: To characterize the short- and long-term outcome (>12 months), complications, and owner satisfaction following prophylactic laparoscopic-assisted gastropexy (LAG) in dogs. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned dogs (n = 49). METHODS: Dogs that underwent prophylactic LAG at 2 veterinary academic hospitals were studied. Surgical time, anesthesia time, concurrent intra- and extra-abdominal procedures, and intraoperative and postoperative complications were recorded following review of medical records. Veterinarian and/or owner follow-up was obtained to determine outcome and satisfaction with LAG. RESULTS: Five of 49 dogs (10%) experienced complications related to abdominal access during LAG. Four percent (2/49) of dogs experienced an intraoperative complication. Follow-up information was available for 89% of dogs (44/49). Four dogs died of causes unrelated to LAG or gastric dilatation volvulus (GDV) in the follow-up period. Two dogs experienced major postoperative complications requiring additional veterinary intervention. Thirty percent (13 dogs) experienced a minor postoperative self-limiting wound-related complication. Median follow-up time was 698 days (range, 411-1825). No dogs experienced GDV. One hundred percent of dog owners were satisfied with LAG, would repeat the procedure in a future pet, and would recommend the procedure to a friend or family member. CONCLUSION: LAG was an effective procedure for prevention of GDV and was associated with high client satisfaction in this cohort of dogs. A moderate rate of postoperative wound complications occurred that were minor and self-limiting in nature.


Assuntos
Doenças do Cão/cirurgia , Dilatação Gástrica/veterinária , Gastropexia/veterinária , Complicações Intraoperatórias/veterinária , Complicações Pós-Operatórias/veterinária , Procedimentos Cirúrgicos Profiláticos/veterinária , Volvo Gástrico/veterinária , Animais , Cães , Feminino , Dilatação Gástrica/cirurgia , Gastropexia/efeitos adversos , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Masculino , Ontário , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ilha do Príncipe Eduardo , Procedimentos Cirúrgicos Profiláticos/efeitos adversos , Estudos Retrospectivos , Volvo Gástrico/cirurgia , Resultado do Tratamento
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