Abstract | BACKGROUND: METHODS: In a marginal mass islet transplantation model, islets from C57BL/6 mice were cotransplanted with CP-ASCs into syngeneic streptozotocin-treated diabetic mice. Treatment response was defined by the percentage of recipients reaching normoglycemia, and by the area under the curve for glucose and c-peptide in a glucose tolerance test. Macrophage infiltration, β-cell apoptosis, and islet graft vasculature were measured in transplanted islet grafts by immunohistochemistry. mRNA expression profiling of 84 apoptosis-related genes in islet grafts transplanted alone or with CP-ASCs was measured by the RT2 Profiler™ Apoptosis PCR Array. The impact of insulin-like growth factor-1 (IGF-1) on islet apoptosis was determined in islets stimulated with cytokines (IL-1β and IFN-γ) in the presence and absence of CP-ASC conditioned medium. RESULTS: CP-ASC-treated mice were more often normoglycemic compared to mice receiving islets alone. ASC cotransplantation reduced macrophage infiltration, β-cell death, suppressed expression of TNF-α and Bcl-2 modifying factor (BMF), and upregulated expressions of IGF-1 and TNF Receptor Superfamily Member 11b (TNFRSF11B) in islet grafts. Islets cultured in conditioned medium from CP-ASCs showed reduced cell death. This protective effect was diminished when IGF-1 was blocked in the conditioned medium by the anti-IGF-1 antibody. CONCLUSION:
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Authors | Lili Song, Zhen Sun, Do-Sung Kim, Wenyu Gou, Charlie Strange, Huansheng Dong, Wanxing Cui, Gary Gilkeson, Katherine A Morgan, David B Adams, Hongjun Wang |
Journal | Stem cell research & therapy
(Stem Cell Res Ther)
Vol. 8
Issue 1
Pg. 192
(08 30 2017)
ISSN: 1757-6512 [Electronic] England |
PMID | 28854965
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Cytokines
- Inflammation Mediators
- Insulin-Like Growth Factor I
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Topics |
- Adipose Tissue
(cytology)
- Animals
- Apoptosis
(genetics)
- Coculture Techniques
- Cytokines
(metabolism)
- Gene Expression Profiling
- Humans
- Inflammation Mediators
(metabolism)
- Insulin-Like Growth Factor I
(metabolism)
- Islets of Langerhans
(physiology)
- Islets of Langerhans Transplantation
- Macrophages
(metabolism)
- Male
- Mice, Inbred C57BL
- Mice, Inbred NOD
- Mice, SCID
- Pancreatitis, Chronic
(parasitology)
- Paracrine Communication
- Stem Cell Transplantation
- Stem Cells
(cytology)
- Tissue Survival
- Transplantation, Autologous
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