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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

Intramuscular transplanted islets at POD 3.A. A large number of inflammatory infiltrates (yellow circle) were observed surrounding islets with a number of islets found to have underwent necrosis in the islets-only group. B. Islets in the GFR Matrigel and Matrigel groups were separated from surrounding inflammatory cells by extracellular matrix. Few necrotic islets were observed in the Matrigel groups. Upper panel, hematoxylin and eosin. Lower panel, insulin immunohistochemistry. Scale bar, 100 μm. POD, postoperative day.
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pone.0140910.g005: Intramuscular transplanted islets at POD 3.A. A large number of inflammatory infiltrates (yellow circle) were observed surrounding islets with a number of islets found to have underwent necrosis in the islets-only group. B. Islets in the GFR Matrigel and Matrigel groups were separated from surrounding inflammatory cells by extracellular matrix. Few necrotic islets were observed in the Matrigel groups. Upper panel, hematoxylin and eosin. Lower panel, insulin immunohistochemistry. Scale bar, 100 μm. POD, postoperative day.

Mentions: Fig 5 shows HE and insulin immunohistochemistry in intramuscularly transplanted islets at POD 3. Substantial inflammatory infiltrates were observed adjacent to islets with a number of necrotic islets in the islets-only group (Fig 5A), whereas islets in the GFR Matrigel and Matrigel groups were separated from inflammatory cells by ECM. Few necrotic islets were seen in the GFR Matrigel and Matrigel groups (Fig 5B).


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)

Intramuscular transplanted islets at POD 3.A. A large number of inflammatory infiltrates (yellow circle) were observed surrounding islets with a number of islets found to have underwent necrosis in the islets-only group. B. Islets in the GFR Matrigel and Matrigel groups were separated from surrounding inflammatory cells by extracellular matrix. Few necrotic islets were observed in the Matrigel groups. Upper panel, hematoxylin and eosin. Lower panel, insulin immunohistochemistry. Scale bar, 100 μm. POD, postoperative day.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140910.g005: Intramuscular transplanted islets at POD 3.A. A large number of inflammatory infiltrates (yellow circle) were observed surrounding islets with a number of islets found to have underwent necrosis in the islets-only group. B. Islets in the GFR Matrigel and Matrigel groups were separated from surrounding inflammatory cells by extracellular matrix. Few necrotic islets were observed in the Matrigel groups. Upper panel, hematoxylin and eosin. Lower panel, insulin immunohistochemistry. Scale bar, 100 μm. POD, postoperative day.
Mentions: Fig 5 shows HE and insulin immunohistochemistry in intramuscularly transplanted islets at POD 3. Substantial inflammatory infiltrates were observed adjacent to islets with a number of necrotic islets in the islets-only group (Fig 5A), whereas islets in the GFR Matrigel and Matrigel groups were separated from inflammatory cells by ECM. Few necrotic islets were seen in the GFR Matrigel and Matrigel groups (Fig 5B).

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