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

Kaixuan Zhao; Yue Shi; Jia Yu; Lina Yu; Amber MaeI; Yuxin Li; Anthony Kolton; Thomas Joyce; Jon Odorico; Per-Olof Berggren; Shao-Nian Yang

doi:10.1177/09636897211066508

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

Kaixuan Zhao, Yue Shi, Jia Yu, Lina Yu, Amber MaeI, Yuxin Li, Anthony Kolton, Thomas Joyce, Jon Odorico, Per-Olof Berggren, Shao-Nian Yang

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Abstract

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

Original language	English
Pages (from-to)	9636897211066508
Journal	Cell Transplantation
Volume	31
DOIs	https://doi.org/10.1177/09636897211066508
Publication status	Published (in print/issue) - 1 Jan 2022

Bibliographical note

Funding Information:
P-OB is the founder and CEO of the biotech company BioCrine AB. S-NY is a consultant to BioCrine. AK and JO are co-founders of Regenerative Medical Solutions, Inc. and have equity interest in the company. The research reported here was supported in part by funding provided by Regenerative Medical Solutions, Inc. AM, and TJ are employees of Regenerative Medical Solutions, Inc.

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by The Bert von Kantzow Foundation, Diabetes and Wellness Foundation, The ERC-2013-AdG 338936-BetaImage, The Family Erling-Persson Foundation, The Family Knut and Alice Wallenberg Foundation, KI Foundations & Funds, Skandia Insurance Company, Ltd., Strategic Research Program in Diabetes at Karolinska Institutet, The Swedish Diabetes Association, The Swedish Research Council and The Stichting af Jochnick Foundation. RMS has been supported by NIH (NIDDK) SBIR grants (2R44DK104497-02, 1R43DK104497-01, 1R43DK108441-01A1, 1R43DK112472-01, 5R44DK104497-03 and 1R43DK109832-01A1).

Publisher Copyright:
© The Author(s) 2022.

Keywords

backscattering
human induced pluripotent stem cells (hiPSCs)
in vivo confocal microscopy
surrogate islet
the anterior chamber of the eye (ACE)
transplantation
vascularization

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1177_09636897211066508Final published version, 1.49 MBLicence: CC BY

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title = "Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells",

abstract = "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",

keywords = "backscattering, human induced pluripotent stem cells (hiPSCs), in vivo confocal microscopy, surrogate islet, the anterior chamber of the eye (ACE), transplantation, vascularization",

author = "Kaixuan Zhao and Yue Shi and Jia Yu and Lina Yu and Amber MaeI and Yuxin Li and Anthony Kolton and Thomas Joyce and Jon Odorico and Per-Olof Berggren and Shao-Nian Yang",

note = "Funding Information: P-OB is the founder and CEO of the biotech company BioCrine AB. S-NY is a consultant to BioCrine. AK and JO are co-founders of Regenerative Medical Solutions, Inc. and have equity interest in the company. The research reported here was supported in part by funding provided by Regenerative Medical Solutions, Inc. AM, and TJ are employees of Regenerative Medical Solutions, Inc. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by The Bert von Kantzow Foundation, Diabetes and Wellness Foundation, The ERC-2013-AdG 338936-BetaImage, The Family Erling-Persson Foundation, The Family Knut and Alice Wallenberg Foundation, KI Foundations & Funds, Skandia Insurance Company, Ltd., Strategic Research Program in Diabetes at Karolinska Institutet, The Swedish Diabetes Association, The Swedish Research Council and The Stichting af Jochnick Foundation. RMS has been supported by NIH (NIDDK) SBIR grants (2R44DK104497-02, 1R43DK104497-01, 1R43DK108441-01A1, 1R43DK112472-01, 5R44DK104497-03 and 1R43DK109832-01A1). Publisher Copyright: {\textcopyright} The Author(s) 2022.",

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doi = "10.1177/09636897211066508",

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volume = "31",

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T1 - Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells

AU - Zhao, Kaixuan

AU - Shi, Yue

AU - Yu, Jia

AU - Yu, Lina

AU - MaeI, Amber

AU - Li, Yuxin

AU - Kolton, Anthony

AU - Joyce, Thomas

AU - Odorico, Jon

AU - Berggren, Per-Olof

AU - Yang, Shao-Nian

N1 - Funding Information: P-OB is the founder and CEO of the biotech company BioCrine AB. S-NY is a consultant to BioCrine. AK and JO are co-founders of Regenerative Medical Solutions, Inc. and have equity interest in the company. The research reported here was supported in part by funding provided by Regenerative Medical Solutions, Inc. AM, and TJ are employees of Regenerative Medical Solutions, Inc. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by The Bert von Kantzow Foundation, Diabetes and Wellness Foundation, The ERC-2013-AdG 338936-BetaImage, The Family Erling-Persson Foundation, The Family Knut and Alice Wallenberg Foundation, KI Foundations & Funds, Skandia Insurance Company, Ltd., Strategic Research Program in Diabetes at Karolinska Institutet, The Swedish Diabetes Association, The Swedish Research Council and The Stichting af Jochnick Foundation. RMS has been supported by NIH (NIDDK) SBIR grants (2R44DK104497-02, 1R43DK104497-01, 1R43DK108441-01A1, 1R43DK112472-01, 5R44DK104497-03 and 1R43DK109832-01A1). Publisher Copyright: © The Author(s) 2022.

PY - 2022/1/1

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N2 - 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

AB - 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

KW - backscattering

KW - human induced pluripotent stem cells (hiPSCs)

KW - in vivo confocal microscopy

KW - surrogate islet

KW - the anterior chamber of the eye (ACE)

KW - transplantation

KW - vascularization

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U2 - 10.1177/09636897211066508

DO - 10.1177/09636897211066508

M3 - Article

C2 - 35156411

SN - 0963-6897

VL - 31

SP - 9636897211066508

JO - Cell Transplantation

JF - Cell Transplantation

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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