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Recent Advances in the Generation of β-Cells from Induced Pluripotent Stem Cells as a Potential Cure for Diabetes Mellitus

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Cell Biology and Translational Medicine, Volume 14

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1347))

Abstract

Diabetes mellitus (DM) is a group of metabolic disorders characterized by high blood glucose levels due to insufficient insulin secretion, insulin action, or both. The present-day solution to diabetes mellitus includes regular administration of insulin, which brings about many medical complications in diabetic patients. Although islet transplantation from cadaveric subjects was proposed to be a permanent cure, the increased risk of infections, the need for immunosuppressive drugs, and their unavailability had restricted its use. To overcome this, the generation of renewable and transplantable β-cells derived from autologous induced pluripotent stem cells (iPSCs) has gained enormous interest as a potential therapeutic strategy to treat diabetes mellitus permanently. To date, extensive research has been undertaken to derive transplantable insulin-producing β-cells (iβ-cells) from iPSCs in vitro by recapitulating the in vivo developmental process of the pancreas. This in vivo developmental process relies on transcription factors, signaling molecules, growth factors, and culture microenvironment. This review highlights the various factors facilitating the generation of mature β-cells from iPSCs. Moreover, this review also describes the generation of pancreatic progenitors and β-cells from diabetic patient–specific iPSCs, exploring the potential of the diabetes disease model and drug discovery. In addition, the applications of genome editing strategies have also been discussed to achieve patient-specific diabetes cell therapy. Last, we have discussed the current challenges and prospects of iPSC-derived β-cells to improve the relative efficacy of the available treatment of diabetes mellitus.

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Abbreviations

4PBA:

4-phenyl butyric acid

ALK:

Activin receptor-like kinase

BMP:

Bone morphogenetic protein

CYC:

KAAD-cyclopamine

DM:

Diabetes mellitus

EGF:

Epidermal growth factor

ER:

Endoplasmic reticulum

FGF:

Fibroblast growth factor

GLP1:

Glucagon-like peptide-1

GLUT2:

Glucose transporter 2

GSIS:

Glucose-stimulated insulin secretion

GSK3β:

Glycogen synthase kinase 3β

HDAC:

Histone deacetylase

HGF:

Hepatocyte growth factor

HIF:

Hypoxia-inducible factor

IBMX:

3-isobutyl-1-methylxanthine

IGF-II:

Insulin-like growth factor II

ILV:

Indolactam V

iPSCs:

Induced pluripotent stem cells

iβ-cells:

Insulin-producing β-cells

KGF:

Keratinocyte growth factor

MAPK:

Mitogen-activated protein kinase

miR:

MicroRNA

MODY:

Maturity-onset diabetes of the young

OSK:

Oct4, Sox2, and Klf4

OSKM:

Oct4, Sox2, Klf4, and c-Myc

PdBU:

Phorbol 12,13-dibutyrate

PI3K:

Phosphoinositide 3-kinase

PLLA/PVA:

Poly-L-lactic acid/polyvinyl alcohol

RA:

Retinoic acid

ROCK:

Rho-associated protein kinase

SHH:

Sonic hedgehog

T1DM:

Type 1 Diabetes mellitus

T2DM:

Type 2 Diabetes mellitus

T3:

Triiodothyronine

TGF-β:

Transforming growth factor-β

WFS:

Wolfram syndrome

WNT3a:

Wingless-related integration site-3a

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Acknowledgments

We thank all the members of the Laboratory for Stem Cell Engineering and Regenerative Medicine (SCERM) for their critical reading and excellent support. This work was financially supported by the Ministry of Science and Technology, Govt. of India (Ref. No.: BT/COE/34/SP28408/2018) under the North East Center for Biological Sciences and Healthcare Engineering (NECBH) outreach program hosted by Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, sponsored by the Department of Biotechnology (DBT), Govt. of India (NECBH/2019-20/136). This work was partially funded by IIT Guwahati Institutional Top-Up on Start-Up Grant.

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Akriti Agrawal and Gloria Narayan were responsible for conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of the manuscript. Ranadeep Gogoi was responsible for data analysis and interpretation, manuscript writing, and final approval of the manuscript, and Rajkumar P Thummer was responsible for conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of the manuscript, and financial support. All the authors gave consent for publication.

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  1. Authors Akriti Agrawal and Gloria Narayan have equally contributed to this chapter.

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  1. Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India

    Akriti Agrawal, Gloria Narayan & Rajkumar P. Thummer

  2. Department of Biotechnology, National Institute of Pharmaceutical Education and Research Guwahati, Changsari, Guwahati, Assam, India

    Ranadeep Gogoi

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  1. Akriti Agrawal
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  1. (emeritus) Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

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Agrawal, A., Narayan, G., Gogoi, R., Thummer, R.P. (2021). Recent Advances in the Generation of β-Cells from Induced Pluripotent Stem Cells as a Potential Cure for Diabetes Mellitus. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 14. Advances in Experimental Medicine and Biology(), vol 1347. Springer, Cham. https://doi.org/10.1007/5584_2021_653

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