Cotransplantation of Mesenchymal Stem Cells With Neonatal Porcine Islets Improve Graft Function in Diabetic Mice
| Autor: | Julie A Hayward, Purushothaman Kuppan, Karen L. Seeberger, Aillette Mulet-Sierra, Cara E Ellis, Bassem Salama, Gregory S. Korbutt, Adetola B Adesida, Tim Y T Lee |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine medicine.medical_specialty Swine Endocrinology Diabetes and Metabolism medicine.medical_treatment Islets of Langerhans Transplantation Neovascularization Physiologic Transplants Biology Mesenchymal Stem Cell Transplantation Diabetes Mellitus Experimental Neovascularization Islets of Langerhans Mice 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Internal medicine Internal Medicine medicine Animals Humans Insulin geography geography.geographical_feature_category Porcine islets Mesenchymal stem cell Diabetic mouse medicine.disease Islet In vitro Diabetes Mellitus Type 1 030104 developmental biology Endocrinology Animals Newborn Immunology medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Diabetes. 66:1312-1321 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db16-1068 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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