Article Text
Abstract
Objective Esterified collagen (EC) can be functionalized with heparin to enhance islet graft stability. Growth factors secreted by human adipose-derived stem cells (hADSCs) can bind efficiently to EC-heparin (EC-Hep), which enhances revascularization and cell protection. We investigated the therapeutic potential of a combined heparin-esterified collagen-hADSC (HCA)-islet sheet to enhance islet engraftment.
Research design and methods This study was designed to assess the efficiency of using EC-Hep as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. After the hADSC-cocultured islets were seeded in the EC-Hep scaffold, islet function was measured by glucose-stimulated insulin secretion test and growth factors in the culture supernatants were detected by protein array. Islet transplantation was performed in mice, and graft function and survival were monitored by measuring the blood glucose levels. β-Cell mass and vascular densities were assessed by immunohistochemistry.
Results The EC-Hep composite allowed sustained release of growth factors. Secretion of growth factors and islet functionality in the HCA-islet sheet were significantly increased compared with the control groups of islets alone or combined with native collagen. In vivo, stable long-term glucose control by the graft was achieved after subcutaneous transplantation of HCA-islet sheet due to enhanced capillary network formation around the sheet.
Conclusions The findings indicate the potential of the HCA-islet sheet to enhance islet revascularization and engraftment in a hADSC dose-dependent manner, following clinical islet transplantation for the treatment of diabetes mellitus.
- human adipose tissue
- bioengineering
- islet transplantation
- revascularization
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Footnotes
YHK, JHK and SL contributed equally.
Contributors YHK: performed research and analyzed data, designed research and interpreted data, wrote the manuscript; JHK and SL: performed research and analyzed data, designed research and interpreted data; JYO, GSJ and S-NP: designed research and interpreted data; SCK and IKS: designed research and interpreted data, supervised data analysis and edited the manuscript.
Funding This work was supported by a grant from Ministry of Science, ICT & Future Planning (2017M3A9C6032060) and Asan Institute for Life Science (2018–7001).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the Asan Medical Center Institutional Review Board (IRB: 2012–0244). All animal experiments were approved by the Institutional Animal Care and Use Committee of Asan Medical Center (IACUC-2014-13-217).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.