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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.


Related in: MedlinePlus

Condition of intraportally and intramuscularly transplanted islets at POD3.Substantial inflammatory infiltrates adjacent to intramuscularly transplanted islets with hemorrhage around islets were observed. Transplanted islets were observed as clustered aggregates with necrotic and apoptotic islet cells at the center of clusters. Necrotic and apoptotic cells were rarely observed following intrahepatic islet transplantation. Scale bar, 100 μm.
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pone.0140910.g001: Condition of intraportally and intramuscularly transplanted islets at POD3.Substantial inflammatory infiltrates adjacent to intramuscularly transplanted islets with hemorrhage around islets were observed. Transplanted islets were observed as clustered aggregates with necrotic and apoptotic islet cells at the center of clusters. Necrotic and apoptotic cells were rarely observed following intrahepatic islet transplantation. Scale bar, 100 μm.

Mentions: The proportion of mice achieving normoglycemia following intramuscular and intraportal transplantations is shown in Table 2. Normoglycemia was induced with the intraportal transplantation of 200 islets; however, a minimum of 300 intramuscularly transplanted islets was required to induce the same effect. Histological findings at POD 3 revealed substantial inflammatory infiltrates adjacent to intramuscularly transplanted islets. Transplanted islets were observed as clustered aggregates with necrotic cells, observed as cells with eosinophilic cytoplasm and nuclear shedding, and apoptotic cells observed at the center of clustered aggregates. Conversely, while a number of hepatic infarctions were observed following intraportal islet transplantation, necrotic or apoptotic islets were rarely observed following intraportal transplantation (Fig 1).


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)

Condition of intraportally and intramuscularly transplanted islets at POD3.Substantial inflammatory infiltrates adjacent to intramuscularly transplanted islets with hemorrhage around islets were observed. Transplanted islets were observed as clustered aggregates with necrotic and apoptotic islet cells at the center of clusters. Necrotic and apoptotic cells were rarely observed following intrahepatic islet transplantation. Scale bar, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140910.g001: Condition of intraportally and intramuscularly transplanted islets at POD3.Substantial inflammatory infiltrates adjacent to intramuscularly transplanted islets with hemorrhage around islets were observed. Transplanted islets were observed as clustered aggregates with necrotic and apoptotic islet cells at the center of clusters. Necrotic and apoptotic cells were rarely observed following intrahepatic islet transplantation. Scale bar, 100 μm.
Mentions: The proportion of mice achieving normoglycemia following intramuscular and intraportal transplantations is shown in Table 2. Normoglycemia was induced with the intraportal transplantation of 200 islets; however, a minimum of 300 intramuscularly transplanted islets was required to induce the same effect. Histological findings at POD 3 revealed substantial inflammatory infiltrates adjacent to intramuscularly transplanted islets. Transplanted islets were observed as clustered aggregates with necrotic cells, observed as cells with eosinophilic cytoplasm and nuclear shedding, and apoptotic cells observed at the center of clustered aggregates. Conversely, while a number of hepatic infarctions were observed following intraportal islet transplantation, necrotic or apoptotic islets were rarely observed following intraportal transplantation (Fig 1).

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.


Related in: MedlinePlus