Indirect co‐culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells

Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The curre...

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Veröffentlicht in:Cell biochemistry and function 2023-04, Vol.41 (3), p.296-308
Hauptverfasser: Sabet Sarvestani, Fatemeh, Tamaddon, Ali‐Mohammad, Yaghoobi, Ramin, Geramizadeh, Bita, Abolmaali, Samira Sadat, Kaviani, Maryam, Keshtkar, Somayeh, Pakbaz, Sara, Azarpira, Negar
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container_issue 3
container_start_page 296
container_title Cell biochemistry and function
container_volume 41
creator Sabet Sarvestani, Fatemeh
Tamaddon, Ali‐Mohammad
Yaghoobi, Ramin
Geramizadeh, Bita
Abolmaali, Samira Sadat
Kaviani, Maryam
Keshtkar, Somayeh
Pakbaz, Sara
Azarpira, Negar
description Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM‐MSCS with angiomiR‐126 and ‐210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow‐mesenchymal stem cells (BM‐MSCs), followed by 3‐day indirect co‐culturing with islets laden in collagen (Col)‐based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN‐containing scaffolds, particularly in the miRNA‐126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM‐MSCs/miRNA‐126 treated group. VEGF was upregulated in the LMN‐containing scaffolds in both miRNA‐treated groups, specifically in the miRNA‐210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN‐free scaffolds; while a drastic downregulation was seen in the LMN‐containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA‐126. LMN‐containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status. Significance statement This study investigated the synergy effect of LMN and angiomiRs on islet cells. It was shown that LMN‐containing scaffolds, once combined with miRNAs‐126 and ‐210 might help islets survive and restore function, thereby enhancing angiogenesis and glycemic status. These data could help to improve islets transplantation state in diabetic conditions.
doi_str_mv 10.1002/cbf.3781
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One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM‐MSCS with angiomiR‐126 and ‐210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow‐mesenchymal stem cells (BM‐MSCs), followed by 3‐day indirect co‐culturing with islets laden in collagen (Col)‐based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN‐containing scaffolds, particularly in the miRNA‐126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM‐MSCs/miRNA‐126 treated group. VEGF was upregulated in the LMN‐containing scaffolds in both miRNA‐treated groups, specifically in the miRNA‐210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN‐free scaffolds; while a drastic downregulation was seen in the LMN‐containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA‐126. LMN‐containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status. Significance statement This study investigated the synergy effect of LMN and angiomiRs on islet cells. It was shown that LMN‐containing scaffolds, once combined with miRNAs‐126 and ‐210 might help islets survive and restore function, thereby enhancing angiogenesis and glycemic status. 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One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM‐MSCS with angiomiR‐126 and ‐210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow‐mesenchymal stem cells (BM‐MSCs), followed by 3‐day indirect co‐culturing with islets laden in collagen (Col)‐based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN‐containing scaffolds, particularly in the miRNA‐126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM‐MSCs/miRNA‐126 treated group. VEGF was upregulated in the LMN‐containing scaffolds in both miRNA‐treated groups, specifically in the miRNA‐210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN‐free scaffolds; while a drastic downregulation was seen in the LMN‐containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA‐126. LMN‐containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status. Significance statement This study investigated the synergy effect of LMN and angiomiRs on islet cells. It was shown that LMN‐containing scaffolds, once combined with miRNAs‐126 and ‐210 might help islets survive and restore function, thereby enhancing angiogenesis and glycemic status. 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subjects Angiogenesis
Autoimmune diseases
Biocompatibility
Bone marrow
bone marrow mesenchymal stem cells
Cell culture
Coculture Techniques
Collagen
Collagen - metabolism
Dextran
Dextrans
Diabetes mellitus
Gene expression
Hydrogels
Insulin
Insulin - metabolism
Insulin secretion
Islet cells
Islets of Langerhans
Laminin
Laminin - metabolism
Laminin - pharmacology
Mesenchymal stem cells
Mesenchymal Stem Cells - metabolism
MicroRNAs
MicroRNAs - metabolism
miRNA
pancreatic islet
Recovery of function
Ribonucleic acid
RNA
Scaffolds
Secretion
Stem cells
Survival
Tissue Scaffolds
Transplantation
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
title Indirect co‐culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells
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