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Extracellular Matrix and Growth Factors Improve the Efficacy of Intramuscular Islet Transplantation.

Tsuchiya H, Sakata N, Yoshimatsu G, Fukase M, Aoki T, Ishida M, Katayose Y, Egawa S, Unno M - PLoS ONE (2015)

Bottom Line: The following three groups were evaluated: islets without treatment (islets-only group), islets embedded in ECM with growth factors (Matrigel group), and islets embedded in ECM without growth factors [growth factor-reduced (GFR) Matrigel group].The viability and insulin-releasing function of islets cultured for 96 h were significantly improved in Matrigel and GFR Matrigel groups compared with the islets-only group.On histological examination, significantly decreased numbers of TdT-mediated deoxyuridine triphosphate-biotin nick end labeling-positive islet cells and significantly increased numbers of Ki67-positive cells were observed in the Matrigel and GFR Matrigel groups at POD 3.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Tohoku University, Sendai, Japan.

ABSTRACT

Background: The efficacy of intramuscular islet transplantation is poor despite being technically simple, safe, and associated with reduced rates of severe complications. We evaluated the efficacy of combined treatment with extracellular matrix (ECM) and growth factors in intramuscular islet transplantation.

Methods: Male BALB/C mice were used for the in vitro and transplantation studies. The following three groups were evaluated: islets without treatment (islets-only group), islets embedded in ECM with growth factors (Matrigel group), and islets embedded in ECM without growth factors [growth factor-reduced (GFR) Matrigel group]. The viability and insulin-releasing function of islets cultured for 96 h were significantly improved in Matrigel and GFR Matrigel groups compared with the islets-only group.

Results: Blood glucose and serum insulin levels immediately following transplantation were significantly improved in the Matrigel and GFR Matrigel groups and remained significantly improved in the Matrigel group at postoperative day (POD) 28. On histological examination, significantly decreased numbers of TdT-mediated deoxyuridine triphosphate-biotin nick end labeling-positive islet cells and significantly increased numbers of Ki67-positive cells were observed in the Matrigel and GFR Matrigel groups at POD 3. Peri-islet revascularization was most prominent in the Matrigel group at POD 14.

Conclusions: The efficacy of intramuscular islet transplantation was improved by combination treatment with ECM and growth factors through the inhibition of apoptosis, increased proliferation of islet cells, and promotion of revascularization.

No MeSH data available.


CD31 staining of intramuscularly transplanted islets at POD 14.(A) Assessment of neovessels directly contiguous with islets. The number of CD31-positive microvessels (arrows) adjacent to islets was significantly higher in the Matrigel group than in the islets-only and GFR Matrigel groups. The number of microvessels adjacent to islets was 4.68 ± 0.47 in the islets-only group, 5.75 ± 0.75 in the Matrigel group, and 8.61 ± 0.75 in the GFR Matrigel group (P = 0.0001 for islets-only vs. Matrigel; P = 0.012 for GFR Matrigel vs. Matrigel). (B) Assessment of islet revascularization. No significant difference in the number of microvessels was observed among the three groups. Scale bar, 100 μm GFR, growth factor reduced; POD, postoperative day.
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pone.0140910.g007: CD31 staining of intramuscularly transplanted islets at POD 14.(A) Assessment of neovessels directly contiguous with islets. The number of CD31-positive microvessels (arrows) adjacent to islets was significantly higher in the Matrigel group than in the islets-only and GFR Matrigel groups. The number of microvessels adjacent to islets was 4.68 ± 0.47 in the islets-only group, 5.75 ± 0.75 in the Matrigel group, and 8.61 ± 0.75 in the GFR Matrigel group (P = 0.0001 for islets-only vs. Matrigel; P = 0.012 for GFR Matrigel vs. Matrigel). (B) Assessment of islet revascularization. No significant difference in the number of microvessels was observed among the three groups. Scale bar, 100 μm GFR, growth factor reduced; POD, postoperative day.

Mentions: Regarding revascularization, the number of CD31-positive microvessels directly contiguous with islets was significantly higher in the Matrigel group compared with the islets-only and GFR Matrigel groups (islets-only, 4.68 ± 0.47 per islet; GFR Matrigel, 5.75 ± 0.75 per islet; Matrigel, 8.61 ± 0.75 per islet; P = 0.0001 for islets-only vs. Matrigel; P = 0.012 for GFR Matrigel vs. Matrigel; Fig 7A). No significant difference in the number of vessels per islet was observed between the three groups (islets-only, 4.08 ± 0.53 × 10−4/μm2; GFR Matrigel, 4.71 ± 0.86 × 10−4/μm2; Matrigel, 4.74 ± 0.40 × 10−4/μm2; Fig 7B). These data indicate the growth factors contained in Matrigel specifically induce revascularization at the site of islet transplantation.


Extracellular Matrix and Growth Factors Improve the Efficacy of Intramuscular Islet Transplantation.

Tsuchiya H, Sakata N, Yoshimatsu G, Fukase M, Aoki T, Ishida M, Katayose Y, Egawa S, Unno M - PLoS ONE (2015)

CD31 staining of intramuscularly transplanted islets at POD 14.(A) Assessment of neovessels directly contiguous with islets. The number of CD31-positive microvessels (arrows) adjacent to islets was significantly higher in the Matrigel group than in the islets-only and GFR Matrigel groups. The number of microvessels adjacent to islets was 4.68 ± 0.47 in the islets-only group, 5.75 ± 0.75 in the Matrigel group, and 8.61 ± 0.75 in the GFR Matrigel group (P = 0.0001 for islets-only vs. Matrigel; P = 0.012 for GFR Matrigel vs. Matrigel). (B) Assessment of islet revascularization. No significant difference in the number of microvessels was observed among the three groups. Scale bar, 100 μm GFR, growth factor reduced; POD, postoperative day.
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pone.0140910.g007: CD31 staining of intramuscularly transplanted islets at POD 14.(A) Assessment of neovessels directly contiguous with islets. The number of CD31-positive microvessels (arrows) adjacent to islets was significantly higher in the Matrigel group than in the islets-only and GFR Matrigel groups. The number of microvessels adjacent to islets was 4.68 ± 0.47 in the islets-only group, 5.75 ± 0.75 in the Matrigel group, and 8.61 ± 0.75 in the GFR Matrigel group (P = 0.0001 for islets-only vs. Matrigel; P = 0.012 for GFR Matrigel vs. Matrigel). (B) Assessment of islet revascularization. No significant difference in the number of microvessels was observed among the three groups. Scale bar, 100 μm GFR, growth factor reduced; POD, postoperative day.
Mentions: Regarding revascularization, the number of CD31-positive microvessels directly contiguous with islets was significantly higher in the Matrigel group compared with the islets-only and GFR Matrigel groups (islets-only, 4.68 ± 0.47 per islet; GFR Matrigel, 5.75 ± 0.75 per islet; Matrigel, 8.61 ± 0.75 per islet; P = 0.0001 for islets-only vs. Matrigel; P = 0.012 for GFR Matrigel vs. Matrigel; Fig 7A). No significant difference in the number of vessels per islet was observed between the three groups (islets-only, 4.08 ± 0.53 × 10−4/μm2; GFR Matrigel, 4.71 ± 0.86 × 10−4/μm2; Matrigel, 4.74 ± 0.40 × 10−4/μm2; Fig 7B). These data indicate the growth factors contained in Matrigel specifically induce revascularization at the site of islet transplantation.

Bottom Line: The following three groups were evaluated: islets without treatment (islets-only group), islets embedded in ECM with growth factors (Matrigel group), and islets embedded in ECM without growth factors [growth factor-reduced (GFR) Matrigel group].The viability and insulin-releasing function of islets cultured for 96 h were significantly improved in Matrigel and GFR Matrigel groups compared with the islets-only group.On histological examination, significantly decreased numbers of TdT-mediated deoxyuridine triphosphate-biotin nick end labeling-positive islet cells and significantly increased numbers of Ki67-positive cells were observed in the Matrigel and GFR Matrigel groups at POD 3.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Tohoku University, Sendai, Japan.

ABSTRACT

Background: The efficacy of intramuscular islet transplantation is poor despite being technically simple, safe, and associated with reduced rates of severe complications. We evaluated the efficacy of combined treatment with extracellular matrix (ECM) and growth factors in intramuscular islet transplantation.

Methods: Male BALB/C mice were used for the in vitro and transplantation studies. The following three groups were evaluated: islets without treatment (islets-only group), islets embedded in ECM with growth factors (Matrigel group), and islets embedded in ECM without growth factors [growth factor-reduced (GFR) Matrigel group]. The viability and insulin-releasing function of islets cultured for 96 h were significantly improved in Matrigel and GFR Matrigel groups compared with the islets-only group.

Results: Blood glucose and serum insulin levels immediately following transplantation were significantly improved in the Matrigel and GFR Matrigel groups and remained significantly improved in the Matrigel group at postoperative day (POD) 28. On histological examination, significantly decreased numbers of TdT-mediated deoxyuridine triphosphate-biotin nick end labeling-positive islet cells and significantly increased numbers of Ki67-positive cells were observed in the Matrigel and GFR Matrigel groups at POD 3. Peri-islet revascularization was most prominent in the Matrigel group at POD 14.

Conclusions: The efficacy of intramuscular islet transplantation was improved by combination treatment with ECM and growth factors through the inhibition of apoptosis, increased proliferation of islet cells, and promotion of revascularization.

No MeSH data available.