AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.2996
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REVIEW

Decoding and understanding molecular mechanisms: Cell signaling pathways, pancreatic β-cell regeneration, and stem cell niche engineering for diabetes

Rajiv Kumar1* ,  Gerardo Caruso2
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1 Faculty of Science, University of Delhi, New Delhi, India
2 Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Unit of Neurosurgery, University of Messina, Messina, Sicily
GPD 2024, 3(2), 2996 https://doi.org/10.36922/gpd.2996
Submitted: 22 February 2024 | Accepted: 26 March 2024 | Published: 6 June 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Stem cell bioengineering addresses regenerative medicine and cellular therapies by applying advanced techniques to stem-cell-derived systems. Despite their promise, stem cell applications are limited by incomplete knowledge. Stem cells and phytochemicals show potential in treating diabetes by halting β-cell degeneration and promoting endogenous islet regeneration. Current diabetes cell therapies include stem cells, mature pancreatic cells, endocrine progenitors, and β-cells, with researchers actively seeking new cell sources for clinically relevant β-cells. Stem cell-derived pancreatic cells are particularly promising for pancreatic islet regeneration. Diabetes mellitus results from cell loss or malfunction: Type 1 diabetes stems from autoimmune damage, whereas Type 2 diabetes is largely attributed to cell malfunction or insulin resistance. The only operative therapy, islet transplantation, necessitates lifelong immune suppression. Significant progress has been made in strategies for therapeutic adult β-cell regeneration. This review assesses studies on cellular signaling pathways linked to β-cell survival and proliferation, exploring regenerative medicine methodologies for pancreatic islet replacement or regeneration. While the “replacement” technique involves cell transplantation, the “regeneration” strategy preserves cell populations through replication. Moreover, artemether and gamma-aminobutyric acid induce pancreatic cells to adopt β-cell-like phenotypes, potentially aiding in the development of new β-cell-like cells for treating severe diabetes in rats. Understanding G-protein-coupled receptor activation pathways is crucial, as new treatment strategies for insulin-dependent diabetic mellitus may emerge from this knowledge.

Keywords
Stem cell bioengineering
Cell signaling pathways
Stem cell niche
Pancreatic β cell regeneration
Clinical and preclinical agents
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Kochar IS, Jain R. Pancreas transplant in type 1 diabetes mellitus: The emerging role of islet cell transplant. Ann Pediatr Endocrinol Metab. 2021;26:86-91. doi: 10.6065/apem.2142012.006

 

  1. Balboa D, Barsby T, Lithovius V, et al. Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Nat Biotechnol. 2022;40:1042-1055. doi: 10.1038/s41587-022-01219-z

 

  1. Tewary M, Shakiba N, Zandstra PW. Stem cell bioengineering: Building from stem cell biology. Nat Rev Genet. 2018;19:595-614. doi: 10.1038/s41576-018-0040-z.

 

  1. Khand BK, Bhonde RR. Can functionally mature islet β-cells be derived from pluripotent stem cells? A step towards ready-to-use β-cells in type 1 diabetes. Curr Stem Cell Res Ther. 2020;16:231-237. doi: 10.2174/1574888x15666200621171726

 

  1. Hamada S, Matsumoto R and Masamune A. Pancreatic stellate cells and metabolic alteration: Physiology and pathophysiology. Front Physiol. 2022;13:865105. doi: 10.3389/fphys.2022.865105

 

  1. Sim EZ, Shiraki N, Kume S. Recent progress in pancreatic islet cell therapy. Inflamm Regen. 2021;41:1. doi: 10.1186/s41232-020-00152-5

 

  1. Lombardo C, Perrone VG, Amorese G, et al. Update on pancreatic transplantation on the management of diabetes. Minerva Med. 2017;108:405-414. doi: 10.23736/S0026-4806.17.05224-7

 

  1. Adams GB, Martin RP, Alley IR, et al. Therapeutic targeting of a stem cell niche. Nat Biotechnol. 2007;25:238-243. doi: 10.1038/nbt1281

 

  1. Kimani CN, Reuter H, Kotzé SH, Muller CJ. Regeneration of pancreatic beta cells by modulation of molecular targets using plant-derived compounds: Pharmacological mechanisms and clinical potential. Curr Issues Mol Biol. 2023;45:6216-6245. doi: 10.3390/cimb45080392

 

  1. Thor D. G protein-coupled receptors as regulators of pancreatic islet functionality. Biochim Biophys Acta Mol Cell Res. 2022;1869:119235. doi: 10.1016/j.bbamcr.2022.119235

 

  1. Jiang WJ, Peng YC, Yang KM. Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes (Review). Exp Ther Med. 2018;16:3275-3285. doi: 10.3892/etm.2018.6603

 

  1. Herranz N, Gil J. Mechanisms and functions of cellular senescence. J Clin Invest. 2018;128:1238-1246. doi: 10.1172/JCI95148

 

  1. Kumar R. Ischemia-reperfusion injury: A mechanistic concept. Atheroscler Open Access. 2021;6:4. doi: 10.4172/asoa.1000153

 

  1. Wang KL, Tao M, Wei TJ, Wei R. Pancreatic β cell regeneration induced by clinical and preclinical agents. World J Stem Cells. 2021;13:64-77. doi: 10.4252/wjsc.v13.i1.64

 

  1. Gasteiger J, Engel T. Applied Chemoinformatics: Achievements and Future Opportunities. United States: Wiley; 2018. doi: 10.1002/9783527806539.ch6h

 

  1. Drawnel FM, Boccardo S, Prummer M, et al. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells. Cell Rep. 2014;9:810-821. doi: 10.1016/j.celrep.2014.09.055.

 

  1. Rajiv K. Host-environment interface, host defense, and mast cell: Autoimmunity, allergy, inflammation, and immune response. JSM Clin Pharm. 2021;5:1018.

 

  1. Yang B, Covington BA, Chen W. In vivo generation and regeneration of β cells in zebrafish. Cell Regen. 2020;9:9. doi: 10.1186/s13619-020-00052-6

 

  1. Nawaz M, Shah N, Zanetti B, et al. Extracellular vesicles and matrix remodeling enzymes: The Emerging roles in extracellular matrix remodeling, progression of diseases and tissue repair. Cells. 2018;7:167. doi: 10.3390/cells7100167

 

  1. Ul-Haq Z, Madura JD. Frontiers in Computational Chemistry. Netherlands: Elsevier Inc.; 2015. doi: 10.2174/97816810816701170301

 

  1. Chueng ST, Yang L, Zhang Y, Lee KB. Multidimensional nanomaterials for the control of stem cell fate. Nano Converg. 2016;3:23. doi: 10.1186/s40580-016-0083-9.

 

  1. Gillespie PG, Müller U. Mechanotransduction by hair cells: Models, molecules, and mechanisms. Cell. 2009;139:33-44. doi: 10.1016/j.cell.2009.09.010

 

  1. Farahzadi R, Valipour B, Montazersaheb S, Fathi E. Targeting the stem cell niche micro-environment as therapeutic strategies in aging. Front Cell Dev Biol. 2023;111162136. doi: 10.3389/fcell.2023.1162136

 

  1. Madl CM, Heilshorn SC. Bioorthogonal strategies for engineering extracellular matrices. Adv Funct Mater. 2018;28:1706046. doi: 10.1002/adfm.201706046

 

  1. Kumar N, Kumar R. Nanotechnology and Nanomaterials in the Treatment of Life-Threatening Diseases. Netherlands: Elsevier; 2013. doi: 10.1016/C2013-0-13374-0

 

  1. Weersma RK, Zhernakova A, Fu J. Interaction between drugs and the gut microbiome. Gut. 2020;69:1510-1519. doi: 10.1136/gutjnl-2019-320204

 

  1. Kumar R, Gulia K. The convergence of nanotechnology‐stem cell, nanotopography‐mechanobiology, and biotic‐abiotic interfaces: Nanoscale tools for tackling the top killer, arteriosclerosis, strokes, and heart attacks. Nano Sel. 2021;2:655-687. doi: 10.1002/nano.202000192

 

  1. Kumar R. Emerging role of neutrophils in wound healing and tissue repair: The routes of healing. Biomed J Sci Tech Res. 2021;36:28687-28688. doi: 10.26717/BJSTR.2021.36.005877

 

  1. Unlu G, Levic DS, Melville DB, Knapik EW. Trafficking mechanisms of extracellular matrix macromolecules: Insights from vertebrate development and human diseases. Int J Biochem Cell Biol. 2014;47:57-67. doi: 10.1016/j.biocel.2013.11.005

 

  1. Ju F, Atyah MM, Horstmann N, et al. Characteristics of the cancer stem cell niche and therapeutic strategies. Stem Cell Res Ther. 2022;13:233. doi: 10.1186/s13287-022-02904-1

 

  1. Blank U, Karlsson G, Karlsson S. Signaling pathways governing stem-cell fate. Blood. 2008;111:492-503. doi: 10.1182/blood-2007-07-075168

 

  1. Thangadurai, D, Sangeetha J. Genomics and Proteomics: Principles, Technologies, and Applications. United States: CRC Press; 2015. doi: 10.1201/b18597

 

  1. Petukhov PA. Cheminformatics approaches to virtual screening. J Am Chem Soc. 2009;131:3407-3408. doi: 10.1021/ja9007326

 

  1. Vining KH, Mooney DJ. Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol. 2017;18:728-742. doi: 10.1038/nrm.2017.108

 

  1. Borlongan CV, Steinberg GK. Editorial: Stem cells and aging. Front Aging Neurosci. 2021;13:690613. doi: 10.3389/fnagi.2021.690613

 

  1. Kumar R. Molecular entities of antimicrobial drugsand resistance mechanism underlying: Bioaccessibility, bioavailability, and bioaccumulation. Int J Bioorg Med Chem. 2021;1:17-19.

 

  1. Mammucari C, Rizzuto R. Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev. 2010;131:536-543. doi: 10.1016/j.mad.2010.07.003

 

  1. Lustig A, Margi R, Orlov A, Orlova D, Azaria L, Gefen A. The mechanobiology theory of the development of medical device-related pressure ulcers revealed through a cell-scale computational modeling framework. Biomech Model Mechanobiol. 2021;20:851-860. doi: 10.1007/s10237-021-01432-w

 

  1. Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: Past, present, and future. Stem Cell Res Ther. 2019;10:68. doi: 10.1186/s13287-019-1165-5

 

  1. Dorland YL, Huveneers S. Cell-cell junctional mechanotransduction in endothelial remodeling. Cell Mol Life Sci. 2016;74:279-292. doi: 10.1007/s00018-016-2325-8.

 

  1. Wu J, Han Y, Zou X, et al. Silica nanoparticles as an enhancer in the IL-1β-induced inflammation cycle of A549 cells. Immunopharmacol Immunotoxicol. 2019;41:199-206. doi: 10.1080/08923973.2019.1569046

 

  1. Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell. 2009;5:17-26. doi: 10.1016/j.stem.2009.06.016

 

  1. Gurevich VV, Gurevich EV. Biased GPCR signaling: Possible mechanisms and inherent limitations. Pharmacol Ther. 2020;211:107540. doi: 10.1016/j.pharmthera.2020.107540

 

  1. Cuminetti V, Arranz L. Bone marrow adipocytes: The enigmatic components of the hematopoietic stem cell niche. J Clin Med. 2019;8:707. doi: 10.3390/jcm8050707

 

  1. Min Wei X, Wumaier G, Zhu N, et al. Protein tyrosine phosphatase L1 represses endothelial-mesenchymal transition by inhibiting IL-1β/NF-κB/Snail signaling. Acta Pharmacol Sin. 2020;41:1102-1110. doi: 10.1038/s41401-020-0374-x

 

  1. Varshavsky A. The N-end rule pathway and regulation by proteolysis. Protein Sci. 2011;20:1298-1345. doi: 10.1002/pro.666

 

  1. Kumar R, Chhikara BS, Gulia K, Chhillar M. Review of nanotheranostics for molecular mechanisms underlying psychiatric disorders and commensurate nanotherapeutics for neuropsychiatry: The mind knockout. Nanotheranostics. 2021;5:288-308. doi: 10.7150/ntno.49619

 

  1. Lal M, Caplan M. Regulated intramembrane proteolysis: Signaling pathways and biological functions. Physiology (Bethesda). 2011;26:34-44. doi: 10.1152/physiol.00028.2010

 

  1. Strauss R, Hamerlik P, Lieber A, Bartek J. Regulation of stem cell plasticity: Mechanisms and relevance to tissue biology and cancer. Mol Ther. 2012;20:887-897. doi: 10.1038/mt.2012.2

 

  1. Martindale JL, Holbrook NJ. Cellular response to oxidative stress: Signaling for suicide and survival. J Cell Physiol. 2002;192:1-15. doi: 10.1002/jcp.10119

 

  1. Gilfillan AM, Beaven MA. Regulation of mast cell responses in health and disease. Crit Rev Immunol. 2011;31:475-530. doi: 10.1615/critrevimmunol.v31.i6.30

 

  1. Pedro MP, Lund K, Iglesias-Bartolome R. The landscape of GPCR signaling in the regulation of epidermal stem cell fate and skin homeostasis. Stem Cells. 2020;38:1520-1531. doi: 10.1002/stem.3273

 

  1. Verma A, Sharda S, Rathi B, Somvanshi P, Pandey BD. Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach. Sci Rep. 2020;10:15131. doi: 10.1038/s41598-020-71674-8

 

  1. Marano F, Hussain S, Rodrigues-Lima F, Baeza-Squiban A, Boland S. Nanoparticles: Molecular targets and cell signalling. Arch Toxicol. 2011;85:733-741. doi: 10.1007/s00204-010-0546-4

 

  1. Luu W, Sharpe LJ, Gelissen IC, Brown AJ. The role of signalling in cellular cholesterol homeostasis. IUBMB Life. 2013;65:675-684. doi: 10.1002/iub.1182

 

  1. Petrova G, Ferrante A, Gorski J. Cross-reactivity of T cells and its role in the immune system. Crit Rev Immunol. 2012;32:349-372. doi: 10.1615/CritRevImmunol.v32.i4.50

 

  1. Yin T, Li L. The stem cell niches in bone. J Clin Invest. 2006;116:1195-1201. doi: 10.1172/JCI28568

 

  1. Hayward SD, Liu J, Fujimuro M. Notch and Wnt signaling: Mimicry and manipulation by gamma herpesviruses. Sci. STKE. 2006;335:re4. doi: 10.1126/stke.3352006re4

 

  1. Silberstein L, Goncalves KA, Kharchenko PV, et al. Proximity-based differential single-cell analysis of the niche to identify stem/progenitor cell regulators. Cell Stem Cell. 2016;19:530-543. doi: 10.1016/j.stem.2016.07.004

 

  1. Frank CA. Molecular host mimicry and manipulation in bacterial symbionts. FEMS Microbiol. Lett. 2019;366:fnz038. doi: 10.1093/femsle/fnz038

 

  1. Abdolmaleki F, Gheibi Hayat SM, Bianconi V, Johnston TP, Sahebkar A. Atherosclerosis and immunity: A perspective. Trends Cardiovasc Med. 2019;29:363-371. doi: 10.1016/j.tcm.2018.09.017

 

  1. Fu X, Wei S, Wang T, et al. Research status of the orphan G protein coupled receptor 158 and future perspectives. Cells. 2022;11:1334. doi: 10.3390/cells11081334

 

  1. Liu Q, Yan T, Tan X, et al. Genome-Wide Identification and Gene Expression Analysis of the OTU DUB Family in Oryza sativa. Viruses. 2022;14:392. doi: 10.3390/v14020392

 

  1. Kaplan N, Di Salvo J. Coupling between [arginine8- vasopressin-activated increases in protein tyrosine phosphorylation and cellular calcium in A7r5 aortic smooth muscle cells. Arch Biochem Biophys. 1996;326:271-278. doi: 10.1006/abbi.1996.0076

 

  1. Kim A, Knudsen JG, Madara JC, et al. Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes. Elife. 2021;10:e72919. doi: 10.7554/eLife.72919

 

  1. Van Eps N, Altenbach C, Caro LN, et al. Gi-and Gs-coupled GPCRs show different modes of G-protein binding. Proc Natl Acad Sci U S A. 2018;115:2383-2388. doi: 10.1073/pnas.1721896115

 

  1. Stewart A, Fisher RA. Introduction: G Protein-coupled receptors and RGS proteins. Prog Mol Biol Transl Sci. 2015;133:1-11. doi: 10.1016/bs.pmbts.2015.03.002

 

  1. Yang D, Zhou Q, Labroska Q, et al. G protein-coupled receptors: Structure- and function-based drug discovery, signal transduct. Target Ther. 2021;6:7. doi: 10.1038/s41392-020-00435-w

 

  1. Sun X, Bee YM, Lam SW, et al. Effective treatment recommendations for type 2 diabetes management using reinforcement learning: Treatment recommendation model development and validation. J Med Internet Res. 2021;23:e27858. doi: 10.2196/27858.

 

  1. Ghanemi A. Targeting G protein coupled receptor-related pathways as emerging molecular therapies. Saudi Pharm J. 2015;23:115-129. doi: 10.1016/j.jsps.2013.07.007

 

  1. Tuteja N. Signaling through G protein coupled receptors. Plant Signal Behav. 2009;4:942-947. doi: 10.4161/psb.4.10.9530

 

  1. Glennon MC, Bird GS, Kwan CY, Putney JW Jr. Actions of vasopressin and the Ca(2+)-ATPase inhibitor, thapsigargin, on Ca(2+) signaling in hepatocytes. J Biol Chem. 1992;267:8230-8233. doi: 10.1016/s0021-9258(18)42431-3

 

  1. Kimura H, Sakai Y, Fujii T. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab Pharmacokinet. 2018;33:43-48. doi: 10.1016/j.dmpk.2017.11.003

 

  1. Hilger D, Masureel M, Kobilka BK. Structure and dynamics of GPCR signaling complexes. Nat Struct Mol Biol. 2018;25:4-12. doi: 10.1038/s41594-017-0011-7

 

  1. Dolatshad NF, Hellen N, Jabbour RJ, Harding SE, Földes G. G-protein coupled receptor signaling in pluripotent stem cell-derived cardiovascular cells: Implications for disease modeling. Front Cell Dev Biol. 2015;3:76. doi: 10.3389/fcell.2015.00076

 

  1. Hrovatin K, Bastidas-Ponce A, Bakhti M, et al. Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas. Nat Metab. 2023;5:1615-1637. doi: 10.1038/s42255-023-00876-x

 

  1. Rahman MS, Hossain KS, Das S, et al. Role of insulin in health and disease: An update. Int J Mol Sci. 2021;22:6403. doi: 10.3390/ijms22126403
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