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Abstract

Human Pluripotent Stem Cells from Diabetic and Nondiabetics Improve Retinal Pathology in Diabetic Mice †

by
Chang-Hyun Gil
1,2,
Dibyendu Chakraborty
3,
Cristiano P. Vieira
3,
Nutan Prasain
1,4,
Sergio Li Calzi
3,
Seth D. Fortmann
3,5,
Ping Hu
3,
Kimihiko Banno
1,6,
Mohamed Jamal
7,8,
Chao Huang
3,
Micheli S. Sielski
3,
Yang Lin
1,9,
Xinxin Huang
10,11,
Mariana D. Dupont
3,
Jason L. Floyd
3,
Ram Prasad
3,
Ana Leda F. Longhini
3,12,
Trevor J. McGill
13,
Hyung-Min Chung
14,
Michael P. Murphy
2,
Darrell N. Kotton
7,
Michael E. Boulton
3,
Mervin C. Yoder
1,15 and
Maria B. Grant
3,*add Show full author list remove Hide full author list
1
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham (UAB), Birmingham, AL 35294, USA
4
Astellas Institute for Regenerative Medicine (AIRM), Westborough, MA 01581, USA
5
Medical Scientist Training Program (MSTP), School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
6
Department of Physiology II, Nara Medical University, Kashihara, Nara 634-8521, Japan
7
Center for Regenerative Medicine, Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
8
Department of Endodontics, Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates
9
Department of Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, New York, NY 10021, USA
10
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
11
Zhongshan-Xuhui Hospital and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 310104, China
12
Flow Cytometry Core Facility, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA
13
Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239, USA
14
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea
15
Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN 46202, USA
 
add Show full affiliation list
 
remove Hide full affiliation list
*
Author to whom correspondence should be addressed.
†
Presented at Cells, Cells and Nothing but Cells: Discoveries, Challenges and Directions, 6–8 March 2023; Available online: https://cells2023.sciforum.net/.
Biol. Life Sci. Forum 2023, 21(1), 33; https://doi.org/10.3390/blsf2023021033
Published: 14 April 2023
(This article belongs to the Proceedings of Cells, Cells and Nothing but Cells: Discoveries, Challenges and Directions)
Versions Notes

Human-induced pluripotent stem cells (hiPSCs) cells have the proliferative potential and ability to differentiate into numerous cell types. We have previously generated vascular wall-derived reparative cells called endothelial colony-forming cells (ECFCs) from iPSCs derived from well-characterized, healthy, and diabetic individuals [1]. Our studies showed that these human iPSCs incorporate into blood vessels when implanted subcutaneously into immune compromised mice. These cells, of either diabetic or nondiabetic origin, when injected into the vitreous of diabetic mice with retinal damage, are incorporated into retinal blood vessels and restore perfusion to ischemic areas. Our studies also show that iPSCs from diabetic donors are able to function in vivo and that reprogramed diabetic iPSC cells behave similarly to nondiabetic hiPSCs. The iPSC-derived ECFCs improved the electroretinograms of the diabetic mice and their ocular kinetic responses. These studies support the notion that iPSCs of diabetic and nondiabetic origin, when differentiated into ECFCs, can correct vascular dysfunction, which in turn improves key functions of the neural retina.

Author Contributions

Conceptualization: C.-H.G., D.C., N.P., M.C.Y., M.E.B. and M.B.G.; methodology: C.-H.G., D.C., N.P., K.B., Y.L., H.-M.C., M.C.Y. and M.B.G.; investigation: C.-H.G., D.C., C.P.V., N.P., S.L.C., S.D.F., P.H., C.H., M.S.S., Y.L., X.H., M.D.D., J.L.F., R.P., A.L.F.L., T.J.M., M.E.B., M.J. and D.N.K.; writing—original draft: C.-H.G., D.C., N.P., M.C.Y. and M.B.G.; writing—review and editing: C.-H.G., D.C., D.N.K., M.E.B., M.C.Y. and M.B.G.; funding acquisition: M.E.B., D.N.K., M.P.M., M.C.Y. and M.B.G.; supervision: M.C.Y. and M.B.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by National Eye Institute (NEI) [EY012601].

Institutional Review Board Statement

IRB-300000173 University of Alabama.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data will be made available upon request.

Conflicts of Interest

M.C.Y. and N.P. are inventors on a pending patent US20190211304A1 related to this work filed by Indiana University Research and Technology Corp (no. 16/323,722, filed 4 August 2017, published 11 July 2019). M.C.Y. is the scientific founder and holds equity in Vascugen Inc., a biotechnology company deriving regenerative medicine cell therapies from iPSCs.

Reference

  1. Gil, C.-H.; Chakraborty, D.; Vieira, C.P.; Prasain, N.; Calzi, S.L.; Fortmann, S.D.; Hu, P.; Banno, K.; Jamal, M.; Huang, C.; et al. Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice. Sci Adv. 2022, 8, eabm5559. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Gil, C.-H.; Chakraborty, D.; Vieira, C.P.; Prasain, N.; Calzi, S.L.; Fortmann, S.D.; Hu, P.; Banno, K.; Jamal, M.; Huang, C.; et al. Human Pluripotent Stem Cells from Diabetic and Nondiabetics Improve Retinal Pathology in Diabetic Mice. Biol. Life Sci. Forum 2023, 21, 33. https://doi.org/10.3390/blsf2023021033

AMA Style

Gil C-H, Chakraborty D, Vieira CP, Prasain N, Calzi SL, Fortmann SD, Hu P, Banno K, Jamal M, Huang C, et al. Human Pluripotent Stem Cells from Diabetic and Nondiabetics Improve Retinal Pathology in Diabetic Mice. Biology and Life Sciences Forum. 2023; 21(1):33. https://doi.org/10.3390/blsf2023021033

Chicago/Turabian Style

Gil, Chang-Hyun, Dibyendu Chakraborty, Cristiano P. Vieira, Nutan Prasain, Sergio Li Calzi, Seth D. Fortmann, Ping Hu, Kimihiko Banno, Mohamed Jamal, Chao Huang, and et al. 2023. "Human Pluripotent Stem Cells from Diabetic and Nondiabetics Improve Retinal Pathology in Diabetic Mice" Biology and Life Sciences Forum 21, no. 1: 33. https://doi.org/10.3390/blsf2023021033

APA Style

Gil, C. -H., Chakraborty, D., Vieira, C. P., Prasain, N., Calzi, S. L., Fortmann, S. D., Hu, P., Banno, K., Jamal, M., Huang, C., Sielski, M. S., Lin, Y., Huang, X., Dupont, M. D., Floyd, J. L., Prasad, R., Longhini, A. L. F., McGill, T. J., Chung, H. -M., ... Grant, M. B. (2023). Human Pluripotent Stem Cells from Diabetic and Nondiabetics Improve Retinal Pathology in Diabetic Mice. Biology and Life Sciences Forum, 21(1), 33. https://doi.org/10.3390/blsf2023021033

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