Microfluidic vascular formation model for assessing angiogenic capacities of single islets

Author:

Nashimoto Yuji12345ORCID,Konno An4,Imaizumi Takuto4,Nishikawa Kaori5,Ino Kosuke3ORCID,Hori Takeshi1ORCID,Kaji Hirokazu1ORCID,Shintaku Hirofumi56ORCID,Goto Masafumi7,Shiku Hitoshi34ORCID

Affiliation:

1. Institute of Biomaterials and Bioengineering (IBB) Tokyo Medical and Dental University (TMDU) Tokyo Japan

2. Frontier Research Institute for Interdisciplinary Sciences (FRIS) Tohoku University Miyagi Japan

3. Graduate School of Engineering Tohoku University Miyagi Japan

4. Graduate School of Environmental Studies Tohoku University Miyagi Japan

5. Cluster for Pioneering Research, RIKEN Saitama Japan

6. Institute for Life and Medical Sciences Kyoto University Kyoto Japan

7. Division of Transplantation and Regenerative Medicine, Graduate School of Medicine Tohoku University Miyagi Japan

Abstract

AbstractPancreatic 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.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Applied Microbiology and Biotechnology,Bioengineering,Biotechnology

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