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Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

Bruin JE, Saber N, Braun N, Fox JK, Mojibian M, Asadi A, Drohan C, O'Dwyer S, Rosman-Balzer DS, Swiss VA, Rezania A, Kieffer TJ - Stem Cell Reports (2015)

Bottom Line: Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported.All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks.Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

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Gene Expression Profiles Are Similar for hESC-Derived Graft Tissues Exposed to Different LFDs or HFDs In VivoThe gene expression of islet-related genes was assessed in macroencapsulated hESC-derived grafts at 29 weeks post-transplantation from mice fed a LFD (10% fat) or HFD (45% fat, 60% fat, and Western), as well as in adult human islet preparations. All data are presented as the fold change relative to undifferentiated hESCs (H1 cells) using a log scale. Data points from individual mice or different human islet donors are shown as box-and-whisker plots. ∗p < 0.05 for hESC-derived grafts from each diet group versus human islets (one-way ANOVA). See also Tables S2 and S3.
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fig3: Gene Expression Profiles Are Similar for hESC-Derived Graft Tissues Exposed to Different LFDs or HFDs In VivoThe gene expression of islet-related genes was assessed in macroencapsulated hESC-derived grafts at 29 weeks post-transplantation from mice fed a LFD (10% fat) or HFD (45% fat, 60% fat, and Western), as well as in adult human islet preparations. All data are presented as the fold change relative to undifferentiated hESCs (H1 cells) using a log scale. Data points from individual mice or different human islet donors are shown as box-and-whisker plots. ∗p < 0.05 for hESC-derived grafts from each diet group versus human islets (one-way ANOVA). See also Tables S2 and S3.

Mentions: At 29 weeks post-transplantation, hESC-derived grafts had similar or significantly higher levels of islet-related genes compared with human islets and there were no significant differences between grafts from mice fed LFDs or HFDs (Figure 3). The majority of cells within the harvested devices were immunoreactive for the endocrine marker synaptophysin, and a small proportion expressed the ductal marker CK19. Trypsin-positive exocrine cells were rarely observed (Figure 4A). The grafts were largely composed of cells expressing insulin, glucagon, or somatostatin (Figures 4B and 4E), and the percentage of mono-hormonal insulin-positive and glucagon-positive cells was similar between diet groups (Figure 4C). However, we did note a minor but significantly higher percentage of cells that were immunoreactive for both insulin and glucagon in the HFD grafts compared with LFD grafts (Figures 4C and 4D). Aside from these rare polyhormonal cells, exposure to HFDs did not appear to generally influence the maturation state of hESC-derived insulin-secreting cells: the majority of insulin-positive cells in all transplant recipients co-expressed PDX1 (Figure 4F), NKX2.2 (Figure 4G), NKX6.1 (Figure 4H), and MAFA (Figure 4I) at 29 weeks post-transplantation.


Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

Bruin JE, Saber N, Braun N, Fox JK, Mojibian M, Asadi A, Drohan C, O'Dwyer S, Rosman-Balzer DS, Swiss VA, Rezania A, Kieffer TJ - Stem Cell Reports (2015)

Gene Expression Profiles Are Similar for hESC-Derived Graft Tissues Exposed to Different LFDs or HFDs In VivoThe gene expression of islet-related genes was assessed in macroencapsulated hESC-derived grafts at 29 weeks post-transplantation from mice fed a LFD (10% fat) or HFD (45% fat, 60% fat, and Western), as well as in adult human islet preparations. All data are presented as the fold change relative to undifferentiated hESCs (H1 cells) using a log scale. Data points from individual mice or different human islet donors are shown as box-and-whisker plots. ∗p < 0.05 for hESC-derived grafts from each diet group versus human islets (one-way ANOVA). See also Tables S2 and S3.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400611&req=5

fig3: Gene Expression Profiles Are Similar for hESC-Derived Graft Tissues Exposed to Different LFDs or HFDs In VivoThe gene expression of islet-related genes was assessed in macroencapsulated hESC-derived grafts at 29 weeks post-transplantation from mice fed a LFD (10% fat) or HFD (45% fat, 60% fat, and Western), as well as in adult human islet preparations. All data are presented as the fold change relative to undifferentiated hESCs (H1 cells) using a log scale. Data points from individual mice or different human islet donors are shown as box-and-whisker plots. ∗p < 0.05 for hESC-derived grafts from each diet group versus human islets (one-way ANOVA). See also Tables S2 and S3.
Mentions: At 29 weeks post-transplantation, hESC-derived grafts had similar or significantly higher levels of islet-related genes compared with human islets and there were no significant differences between grafts from mice fed LFDs or HFDs (Figure 3). The majority of cells within the harvested devices were immunoreactive for the endocrine marker synaptophysin, and a small proportion expressed the ductal marker CK19. Trypsin-positive exocrine cells were rarely observed (Figure 4A). The grafts were largely composed of cells expressing insulin, glucagon, or somatostatin (Figures 4B and 4E), and the percentage of mono-hormonal insulin-positive and glucagon-positive cells was similar between diet groups (Figure 4C). However, we did note a minor but significantly higher percentage of cells that were immunoreactive for both insulin and glucagon in the HFD grafts compared with LFD grafts (Figures 4C and 4D). Aside from these rare polyhormonal cells, exposure to HFDs did not appear to generally influence the maturation state of hESC-derived insulin-secreting cells: the majority of insulin-positive cells in all transplant recipients co-expressed PDX1 (Figure 4F), NKX2.2 (Figure 4G), NKX6.1 (Figure 4H), and MAFA (Figure 4I) at 29 weeks post-transplantation.

Bottom Line: Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported.All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks.Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Show MeSH
Related in: MedlinePlus