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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.


Islet residual rate, viability, and stimulation index following culture with or without Matrigel.Islets were cultured for 96 h with or without Matrigel before the assessment of residual rate, viability, and the ratio of insulin released in response to stimulation by high and low concentration glucose solutions (SI). (A) The residual rate of islets in the GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. (B) Islet cell viability in GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. Right figures; green: viable cells, red: dead cells. Scale bar, 100 μm. (C) The SI was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group. *P < 0.05. GFR, growth factor reduced; SI, stimulation index.
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pone.0140910.g002: Islet residual rate, viability, and stimulation index following culture with or without Matrigel.Islets were cultured for 96 h with or without Matrigel before the assessment of residual rate, viability, and the ratio of insulin released in response to stimulation by high and low concentration glucose solutions (SI). (A) The residual rate of islets in the GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. (B) Islet cell viability in GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. Right figures; green: viable cells, red: dead cells. Scale bar, 100 μm. (C) The SI was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group. *P < 0.05. GFR, growth factor reduced; SI, stimulation index.

Mentions: Islet residual rates (n = 5 per group) in the GFR Matrigel and Matrigel groups were significantly higher than those in the islets-only group (islets-only, 80.9% ± 2.19%; GFR Matrigel, 97.6% ± 90.36%; Matrigel, 97.5% ± 0.35%; P = 0.0001 for islets-only vs. GFR Matrigel; P = 0.0002 for islets-only vs. Matrigel; Fig 2A). Islet cell viability (n = 5 per group) in the GFR Matrigel and Matrigel groups was significantly higher than that in the islets-only group (islets-only, 88.7% ± 1.16%; GFR Matrigel, 98.1% ± 0.22%; Matrigel, 98.2% ± 0.28%; P = 0.0001 for islets-only vs. GFR Matrigel; P = 0.0001 for islets-only vs. Matrigel; Fig 2B). The SI (n = 4) was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group (islets-only, 1.77 ± 0.39; GFR Matrigel, 4.02 ± 0.54; Matrigel, 3.69 ± 0.45; P = 0.026 for islets-only vs. GFR Matrigel; P = 0.031 for islets-only vs. Matrigel; Fig 2C). These data demonstrate the utility of ECM (regardless of growth factors) in reducing islet injury and preserving islet endocrine function during in vitro culture conditions.


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)

Islet residual rate, viability, and stimulation index following culture with or without Matrigel.Islets were cultured for 96 h with or without Matrigel before the assessment of residual rate, viability, and the ratio of insulin released in response to stimulation by high and low concentration glucose solutions (SI). (A) The residual rate of islets in the GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. (B) Islet cell viability in GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. Right figures; green: viable cells, red: dead cells. Scale bar, 100 μm. (C) The SI was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group. *P < 0.05. GFR, growth factor reduced; SI, stimulation index.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4608691&req=5

pone.0140910.g002: Islet residual rate, viability, and stimulation index following culture with or without Matrigel.Islets were cultured for 96 h with or without Matrigel before the assessment of residual rate, viability, and the ratio of insulin released in response to stimulation by high and low concentration glucose solutions (SI). (A) The residual rate of islets in the GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. (B) Islet cell viability in GFR Matrigel or Matrigel groups was significantly higher than that in the islets-only group. Right figures; green: viable cells, red: dead cells. Scale bar, 100 μm. (C) The SI was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group. *P < 0.05. GFR, growth factor reduced; SI, stimulation index.
Mentions: Islet residual rates (n = 5 per group) in the GFR Matrigel and Matrigel groups were significantly higher than those in the islets-only group (islets-only, 80.9% ± 2.19%; GFR Matrigel, 97.6% ± 90.36%; Matrigel, 97.5% ± 0.35%; P = 0.0001 for islets-only vs. GFR Matrigel; P = 0.0002 for islets-only vs. Matrigel; Fig 2A). Islet cell viability (n = 5 per group) in the GFR Matrigel and Matrigel groups was significantly higher than that in the islets-only group (islets-only, 88.7% ± 1.16%; GFR Matrigel, 98.1% ± 0.22%; Matrigel, 98.2% ± 0.28%; P = 0.0001 for islets-only vs. GFR Matrigel; P = 0.0001 for islets-only vs. Matrigel; Fig 2B). The SI (n = 4) was significantly higher in the GFR Matrigel and Matrigel groups compared with the islets-only group (islets-only, 1.77 ± 0.39; GFR Matrigel, 4.02 ± 0.54; Matrigel, 3.69 ± 0.45; P = 0.026 for islets-only vs. GFR Matrigel; P = 0.031 for islets-only vs. Matrigel; Fig 2C). These data demonstrate the utility of ECM (regardless of growth factors) in reducing islet injury and preserving islet endocrine function during in vitro culture conditions.

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.