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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.


TUNEL and Ki67 immunohistochemistry of intramuscularly transplanted islets at POD 3.(A) The proportion of TUNEL-positive cells (arrows) per islet was significantly lower in the GFR Matrigel and Matrigel groups compared with the islets-only group. The proportion of TUNEL-positive apoptotic cells was 7.50 ± 1.79 in the islets-only group, 1.37 ± 0.65 in the GFR Matrigel group, and 1.01 ± 0.41 in the Matrigel group (P = 0.0014 for islets-only vs. GFR Matrigel; P = 0.0024 for islets-only vs. Matrigel). (B) The proportion of Ki67-positive cells (arrows) per islet was significantly higher in the GFR Matrigel and Matrigel groups than that in the islets-only group. The proportion of Ki67-positive cells per islet was 1.38 ± 0.43 in the islets-only group, 3.80 ± 0.55 in the GFR Matrigel group, and 5.58 ± 1.02 in the Matrigel group (P = 0.001 for islets-only vs. GFR Matrigel; P = 0.00025 for islets-only vs. Matrigel). Scale bar, 100 μm GFR, growth factor reduced; TUNEL, TdT-mediated deoxyuridine triphosphate-biotin nick end labeling.
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pone.0140910.g006: TUNEL and Ki67 immunohistochemistry of intramuscularly transplanted islets at POD 3.(A) The proportion of TUNEL-positive cells (arrows) per islet was significantly lower in the GFR Matrigel and Matrigel groups compared with the islets-only group. The proportion of TUNEL-positive apoptotic cells was 7.50 ± 1.79 in the islets-only group, 1.37 ± 0.65 in the GFR Matrigel group, and 1.01 ± 0.41 in the Matrigel group (P = 0.0014 for islets-only vs. GFR Matrigel; P = 0.0024 for islets-only vs. Matrigel). (B) The proportion of Ki67-positive cells (arrows) per islet was significantly higher in the GFR Matrigel and Matrigel groups than that in the islets-only group. The proportion of Ki67-positive cells per islet was 1.38 ± 0.43 in the islets-only group, 3.80 ± 0.55 in the GFR Matrigel group, and 5.58 ± 1.02 in the Matrigel group (P = 0.001 for islets-only vs. GFR Matrigel; P = 0.00025 for islets-only vs. Matrigel). Scale bar, 100 μm GFR, growth factor reduced; TUNEL, TdT-mediated deoxyuridine triphosphate-biotin nick end labeling.

Mentions: The proportion of TUNEL-positive cells per islet was significantly higher in the islets-only group compared with the Matrigel and GFR Matrigel groups. The proportion of apoptotic cells was 7.50% ± 1.79% in the islets-only group, 1.37% ± 0.65% in the GFR Matrigel group, and 1.01% ± 0.41% in the Matrigel group (P = 0.0014 for islets-only vs. GFR Matrigel; P = 0.0024 for islets-only vs. Matrigel; Fig 6A). In addition, the proportion of Ki67-positive cells per islet was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group (islets-only group, 1.38% ± 0.43%; GFR Matrigel group, 3.80% ± 0.55%; Matrigel group, 5.58% ± 1.02%; P = 0.001 for islets-only vs. GFR Matrigel; P = 0.00025 for islets-only vs. Matrigel; Fig 6B). These data indicate ECM inhibits islet cell apoptosis and promotes proliferation of islet cells.


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)

TUNEL and Ki67 immunohistochemistry of intramuscularly transplanted islets at POD 3.(A) The proportion of TUNEL-positive cells (arrows) per islet was significantly lower in the GFR Matrigel and Matrigel groups compared with the islets-only group. The proportion of TUNEL-positive apoptotic cells was 7.50 ± 1.79 in the islets-only group, 1.37 ± 0.65 in the GFR Matrigel group, and 1.01 ± 0.41 in the Matrigel group (P = 0.0014 for islets-only vs. GFR Matrigel; P = 0.0024 for islets-only vs. Matrigel). (B) The proportion of Ki67-positive cells (arrows) per islet was significantly higher in the GFR Matrigel and Matrigel groups than that in the islets-only group. The proportion of Ki67-positive cells per islet was 1.38 ± 0.43 in the islets-only group, 3.80 ± 0.55 in the GFR Matrigel group, and 5.58 ± 1.02 in the Matrigel group (P = 0.001 for islets-only vs. GFR Matrigel; P = 0.00025 for islets-only vs. Matrigel). Scale bar, 100 μm GFR, growth factor reduced; TUNEL, TdT-mediated deoxyuridine triphosphate-biotin nick end labeling.
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pone.0140910.g006: TUNEL and Ki67 immunohistochemistry of intramuscularly transplanted islets at POD 3.(A) The proportion of TUNEL-positive cells (arrows) per islet was significantly lower in the GFR Matrigel and Matrigel groups compared with the islets-only group. The proportion of TUNEL-positive apoptotic cells was 7.50 ± 1.79 in the islets-only group, 1.37 ± 0.65 in the GFR Matrigel group, and 1.01 ± 0.41 in the Matrigel group (P = 0.0014 for islets-only vs. GFR Matrigel; P = 0.0024 for islets-only vs. Matrigel). (B) The proportion of Ki67-positive cells (arrows) per islet was significantly higher in the GFR Matrigel and Matrigel groups than that in the islets-only group. The proportion of Ki67-positive cells per islet was 1.38 ± 0.43 in the islets-only group, 3.80 ± 0.55 in the GFR Matrigel group, and 5.58 ± 1.02 in the Matrigel group (P = 0.001 for islets-only vs. GFR Matrigel; P = 0.00025 for islets-only vs. Matrigel). Scale bar, 100 μm GFR, growth factor reduced; TUNEL, TdT-mediated deoxyuridine triphosphate-biotin nick end labeling.
Mentions: The proportion of TUNEL-positive cells per islet was significantly higher in the islets-only group compared with the Matrigel and GFR Matrigel groups. The proportion of apoptotic cells was 7.50% ± 1.79% in the islets-only group, 1.37% ± 0.65% in the GFR Matrigel group, and 1.01% ± 0.41% in the Matrigel group (P = 0.0014 for islets-only vs. GFR Matrigel; P = 0.0024 for islets-only vs. Matrigel; Fig 6A). In addition, the proportion of Ki67-positive cells per islet was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group (islets-only group, 1.38% ± 0.43%; GFR Matrigel group, 3.80% ± 0.55%; Matrigel group, 5.58% ± 1.02%; P = 0.001 for islets-only vs. GFR Matrigel; P = 0.00025 for islets-only vs. Matrigel; Fig 6B). These data indicate ECM inhibits islet cell apoptosis and promotes proliferation of islet cells.

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.