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Integration of Primary Endocrine Cells and Supportive Cells Using Functionalized Silk Promotes the Formation of Prevascularized Islet-like Clusters
KTH.
KTH.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
Karolinska Univ Hosp, Stockholm, Sweden..
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2020 (English)In: ACS BIOMATERIALS SCIENCE & ENGINEERING, ISSN 2373-9878, Vol. 6, no 2, p. 1186-1195Article in journal (Refereed) Published
Abstract [en]

Pancreatic islet transplantation has not yet succeeded as an overall treatment for type 1 diabetes because of limited access to donor islets, as well as low efficacy and poor reproducibility of the current procedure. Herein, a method to create islets-like composite clusters (coclusters) from dispersed endocrine cells and supportive cells is described, attempting to improve compatibility with the recipient and more efficiently make use of the donor-derived material. To mimic the extracellular matrix environment, recombinant,spider silk functionalized with cell binding motifs are used as 3D support for the coclusters. A cell binding motif derived from fibronectin (FN) was found superior in promoting cell adherence, while a plain RGD-motif incorporated in the repetitive part of the silk protein (2R) increased the mobility and cluster formation of endocrine cells. Self-assembly of a mixture of FN/2R silk is utilized to integrate endocrine cells together with endothelial and mesenchymal cells into islet-like coclusters. Both xenogenic and allogenic versions of these coclusters were found to be viable and were able to respond to dynamic glucose stimulation with insulin release. Moreover, the endothelial cells were found to be colocalized with the endocrine cells, showing that the silk combined with supportive cells may promote vascularization. This method to engineer combined islet-like coclusters allows donor-derived endocrine cells to be surrounded by supportive cells from the recipient, which have the potential to further promote engraftment in the host and considerably reduce risk of rejection.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2020. Vol. 6, no 2, p. 1186-1195
Keywords [en]
recombinant spider silk, pancreatic islets, islet-like clusters, insulin release, vascularization
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-270884DOI: 10.1021/acsbiomaterials.9b01573ISI: 000513086900037Scopus ID: 2-s2.0-85078673921OAI: oai:DiVA.org:kth-270884DiVA, id: diva2:1416756
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QC 20200325

Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-25Bibliographically approved

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Shalaly, Nancy DekkiHjelm, Linnea C.Hedhammar, My

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Johansson, UlrikaShalaly, Nancy DekkiHjelm, Linnea C.Hedhammar, My
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KTHProtein ScienceCentre for Bioprocess Technology, CBioPTProtein Technology
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