Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells

We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or neg...

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Main Authors: Kaixuan Zhao, Yue Shi, Jia Yu, Lina Yu, Amber Mael, Yuxin Li, Anthony Kolton, Thomas Joyce, Jon Odorico, Per-Olof Berggren, Shao-Nian Yang
Format: Article
Language:English
Published: SAGE Publishing 2022-01-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/09636897211066508
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author Kaixuan Zhao
Yue Shi
Jia Yu
Lina Yu
Amber Mael
Yuxin Li
Anthony Kolton
Thomas Joyce
Jon Odorico
Per-Olof Berggren
Shao-Nian Yang
author_facet Kaixuan Zhao
Yue Shi
Jia Yu
Lina Yu
Amber Mael
Yuxin Li
Anthony Kolton
Thomas Joyce
Jon Odorico
Per-Olof Berggren
Shao-Nian Yang
author_sort Kaixuan Zhao
collection DOAJ
description We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.
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spelling doaj.art-7a6d115ffef14711b7ae33a0c85f8b382022-12-22T01:51:45ZengSAGE PublishingCell Transplantation1555-38922022-01-013110.1177/09636897211066508Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine CellsKaixuan Zhao0Yue Shi1Jia Yu2Lina Yu3Amber Mael4Yuxin Li5Anthony Kolton6Thomas Joyce7Jon Odorico8Per-Olof Berggren9Shao-Nian Yang10 The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden Regenerative Medical Solutions, Inc., Madison, WI, USA National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China Regenerative Medical Solutions, Inc., Madison, WI, USA Regenerative Medical Solutions, Inc., Madison, WI, USA Regenerative Medical Solutions, Inc., Madison, WI, USA The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, ChinaWe exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.https://doi.org/10.1177/09636897211066508
spellingShingle Kaixuan Zhao
Yue Shi
Jia Yu
Lina Yu
Amber Mael
Yuxin Li
Anthony Kolton
Thomas Joyce
Jon Odorico
Per-Olof Berggren
Shao-Nian Yang
Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells
Cell Transplantation
title Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells
title_full Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells
title_fullStr Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells
title_full_unstemmed Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells
title_short Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells
title_sort intracameral microimaging of maturation of human ipsc derivatives into islet endocrine cells
url https://doi.org/10.1177/09636897211066508
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