Microfluidic vascular formation model for assessing angiogenic capacities of single islets.
Yuji NashimotoAn KonnoTakuto ImaizumiKaori NishikawaKosuke InoTakeshi HoriHirokazu KajiHirofumi ShintakuMasafumi GotoHitoshi ShikuPublished in: Biotechnology and bioengineering (2023)
Pancreatic islet transplantation presents a promising therapy for individuals suffering from type 1 diabetes. To maintain the function of transplanted islets in vivo, it is imperative to induce angiogenesis. However, the mechanisms underlying angiogenesis triggered by islets remain unclear. In this study, we introduced a microphysiological system to study the angiogenic capacity and dynamics of individual islets. The system, which features an open-top structure, uniquely facilitates the inoculation of islets and the longitudinal observation of vascular formation in in vivo like microenvironment with islet-endothelial cell communication. By leveraging our system, we discovered notable islet-islet heterogeneity in the angiogenic capacity. Transcriptomic analysis of the vascularized islets revealed that islets with high angiogenic capacity exhibited upregulation of genes related to insulin secretion and downregulation of genes related to angiogenesis and fibroblasts. In conclusion, our microfluidic approach is effective in characterizing the vascular formation of individual islets and holds great promise for elucidating the angiogenic mechanisms that enhance islet transplantation therapy.
Keyphrases
- endothelial cells
- single cell
- type diabetes
- stem cells
- cell proliferation
- vascular endothelial growth factor
- rna seq
- metabolic syndrome
- signaling pathway
- circulating tumor cells
- gene expression
- cell therapy
- mesenchymal stem cells
- machine learning
- transcription factor
- cross sectional
- skeletal muscle
- weight loss
- big data
- high glucose