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1.
Diabetes ; 66(5): 1312-1321, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28246290

RESUMO

Mesenchymal stem cells (MSCs) possess immunoregulatory, anti-inflammatory, and proangiogenic properties and, therefore, have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow-derived MSCs have on neonatal porcine islets (NPIs) in vitro and determined islet engraftment and metabolic outcomes when cotransplanted in a mouse model. NPIs cocultured with MSCs had greater cellular insulin content and increased glucose-stimulated insulin secretion. NPIs were cotransplanted with or without MSCs in diabetic B6.129S7-Rag1tm1Mom/J mice. Blood glucose and weight were monitored until reversal of diabetes; mice were then given an oral glucose tolerance test. Islet grafts were assessed for the degree of vascularization and total cellular insulin content. Cotransplantation of NPIs and MSCs resulted in significantly earlier normoglycemia and vascularization, improved glucose tolerance, and increased insulin content. One experiment conducted with MSCs from a donor with an autoimmune disorder had no positive effects on transplant outcomes. Cotransplantation of human MSCs with NPIs demonstrated a beneficial metabolic effect likely as a result of earlier islet vascularization and improved islet engraftment. In addition, donor pathology of MSCs can influence the functional capacity of MSCs.


Assuntos
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/metabolismo , Transplante de Células-Tronco Mesenquimais , Neovascularização Fisiológica , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/irrigação sanguínea , Masculino , Camundongos , Suínos , Transplantes/irrigação sanguínea
2.
Diabetologia ; 58(7): 1503-12, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25930156

RESUMO

AIMS/HYPOTHESIS: There are potential advantages to the low-temperature (-196 °C) banking of isolated islets, including the maintenance of viable islets for future research. We therefore assessed the in vitro and in vivo function of islets cryopreserved for nearly 20 years. METHODS: Human islets were cryopreserved from 1991 to 2001 and thawed between 2012 and 2014. These were characterised by immunostaining, patch-clamp electrophysiology, insulin secretion, transcriptome analysis and transplantation into a streptozotocin (STZ)-induced mouse model of diabetes. RESULTS: The cryopreservation time was 17.6 ± 0.4 years (n = 43). The thawed islets stained positive with dithizone, contained insulin-positive and glucagon-positive cells, and displayed levels of apoptosis and transcriptome profiles similar to those of freshly isolated islets, although their insulin content was lower. The cryopreserved beta cells possessed ion channels and exocytotic responses identical to those of freshly isolated beta cells. Cells from a subset of five donors demonstrated similar perifusion insulin secretion profiles pre- and post-cryopreservation. The transplantation of cryopreserved islets into the diabetic mice improved their glucose tolerance but did not completely normalise their blood glucose levels. Circulating human insulin and insulin-positive grafts were detectable at 10 weeks post-transplantation. CONCLUSIONS/INTERPRETATION: We have demonstrated the potential for long-term banking of human islets for research, which could enable the use of tissue from a large number of donors with future technologies to gain new insight into diabetes.


Assuntos
Criopreservação , Ilhotas Pancreáticas/fisiologia , Bancos de Tecidos , Adulto , Animais , Diabetes Mellitus Experimental/terapia , Exocitose/fisiologia , Feminino , Proteínas de Homeodomínio/genética , Humanos , Insulina/sangue , Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Canais Iônicos/metabolismo , Transplante das Ilhotas Pancreáticas , Masculino , Camundongos , Camundongos Knockout , Técnicas de Patch-Clamp , Transcriptoma/genética
3.
Genet Med ; 14(9): 765-76, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22498847

RESUMO

PURPOSE: Telemedicine is being increasingly used in many areas of health care, particularly to reduce the barriers that rural populations face in accessing health-care services. Telemedicine may also be effectively utilized in clinical genetics services-an application that has been termed "telegenetics." METHODS: A systematic review of the literature was conducted to identify studies of genetic consultations carried out through videoconferencing so as to determine whether conclusions can be drawn about the value of telegenetics. A total of 14 articles reporting data from 12 separate studies met the inclusion criteria. RESULTS: In a majority of these studies, patients received their telegenetics consultation at a local clinic or outreach center, from where they communicated via a synchronous video link with a genetics practitioner. All the studies reported high levels of patient satisfaction with telegenetics, and patients were generally more receptive to telegenetics than the genetics practitioners were. The studies had limitations of small sample sizes and lack of statistical analyses. CONCLUSIONS: This review suggests that telegenetics may be a useful tool for providing routine counseling and has the potential to evaluate pediatric patients with suspected genetic conditions. Prospective, fully powered studies of telegenetics that explore the accuracy of diagnoses and patient outcomes are needed to allow informed decisions to be made about the appropriate use of telemedicine in genetics service delivery.


Assuntos
Serviços em Genética/normas , Telemedicina/métodos , Aconselhamento Genético , Humanos , Pediatria , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Comunicação por Videoconferência
4.
Genet Med ; 14(9): 765-76, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23393646

RESUMO

PURPOSE: Telemedicine is being increasingly used in many areas of health care, particularly to reduce the barriers that rural populations face in accessing health-care services. Telemedicine may also be effectively utilized in clinical genetics services­an application that has been termed "telegenetics." METHODS: A systematic review of the literature was conducted to identify studies of genetic consultations carried out through video conferencing so as to determine whether conclusions can be drawn about the value of telegenetics. A total of 14 articles reporting data from 12 separate studies met the inclusion criteria. RESULTS: In a majority of these studies, patients received their telegenetics consultation at a local clinic or outreach center, from where they communicated via a synchronous video link with a genetic spractitioner. All the studies reported high levels of patient satisfaction with telegenetics,and patients were generally more receptive to telegenetics than the genetics practitioners were. The studies had limitations of small sample sizes and lack of statistical analyses. CONCLUSIONS: This review suggests that telegenetics may be a useful tool for providing routine counseling and has the potential to evaluate pediatric patients with suspected genetic conditions. Prospective,fully powered studies of telegenetics that explore the accuracy of diagnoses and patient outcomes are needed to allow informed decisions to be made about the appropriate use of telemedicine in genetics service delivery.


Assuntos
Aconselhamento Genético/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Comunicação por Videoconferência/estatística & dados numéricos , Adulto , Criança , Aconselhamento Genético/economia , Aconselhamento Genético/organização & administração , Humanos , Satisfação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Encaminhamento e Consulta , População Rural , Inquéritos e Questionários , Telemedicina/economia , Telemedicina/organização & administração , Comunicação por Videoconferência/economia , Comunicação por Videoconferência/organização & administração
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