Stem Cell-Based Therapies: A New Ray of Hope for Diabetic Patients

Author(s): Junaid Khan, Amit Alexander*, Mukta Agrawal, Ajazuddin, Sunil Kumar Dubey, Sabahuddin Siddique, Swarnlata Saraf, Shailendra Saraf

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 2 , 2019

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Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing β cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

Keywords: Stem cell, diabetes, insulin, β cells regeneration, tissue regeneration, patients.

Christopher JB, Shanta JP, Peter MJ. Diabetes Mellitus: A potential target for stem cell therapy. Curr Stem Cell Res Ther 2006; 1(2): 255-66.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103(2): 137-49.
Giri T, Alexander A, Agrawal M, Saraf S. Current status of stem cell therapies in tissue repair and regeneration. Curr Stem Cell Res Ther 2018.
Shuyu Ng C, Toh MP, Ko Y, Yu-Chia Lee J. Direct medical cost of type 2 diabetes in singapore. PLoS One 2015; 10(3): e0122795.
Yue J, Mao X, Xu K, et al. Prevalence, Awareness, Treatment and Control of Diabetes Mellitus in a Chinese Population. PLoS One 2016; 11(4): e0153791.
Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants. Lancet (London, England) 2016; 387(10027): 1513-30.
Leyla Turker S, Isil A. Challenge of mesenchymal stem cells against diabetic foot ulcer. Curr Stem Cell Res Ther 2015; 10(6): 530-4.
Ramachandran A, Snehalatha C, Shetty AS, Nanditha A. Trends in prevalence of diabetes in Asian countries. World J Diabetes 2012; 3(6): 110-7.
Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: A review of current trends. Oman Med J 2012; 27(4): 269-73.
Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci 2014; 11(11): 1185-200.
Muhammad Shareef M, Muhammad Q, Muhammad Umar A. Translating the potential of stem cells for diabetes mellitus: Challenges and opportunities. Curr Stem Cell Res Ther 2017; 12(8): 611-23.
Lozito TP, Tuan RS. Lizard tail regeneration as an instructive model of enhanced healing capabilities in an adult amniote. Connect Tissue Res 2017; 58(2): 145-54.
Christ GJ, Saul JM, Furth ME, Andersson KE. The pharmacology of regenerative medicine. Pharmacol Rev 2013; 65(3): 1091-133.
Albiero M, Avogaro A, Fadini GP. Restoring stem cell mobilization to promote vascular repair in diabetes. Vascul Pharmacol 2013; 58(4): 253-8.
Kumar R, Sharma A, Pattnaik AK, Varadwaj PK. Stem cells: An overview with respect to cardiovascular and renal disease. J Nat Sci Biol Med 2010; 1(1): 43-52.
Alexander A, Saraf S, Agrawal M, Patel R, Agrawal P, Khan J. Amalgamation of stem cells with nanotechnology: A unique therapeutic approach. Curr Stem Cell Res Ther 2018. [Epub ahead of print].
Biancamaria L, Franco M. Stem Cell-Based Immunomodulation in Type 1 Diabetes: Beyond the regenerative approach. Curr Pharm Des 2011; 17(29): 3229-42.
Chhabra P, Brayman KL. Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med 2013; 2(5): 328-36.
Anandwardhan AH, Justin GL, Kuldip SS, Emily C, Bernard ET. Stem-cell therapy for diabetes cure: How close are we? Curr Stem Cell Res Ther 2006; 1(3): 425-36.
Condic ML. Totipotency: What it is and what it is not. Stem Cells Dev 2014; 23(8): 796-812.
de Kretser D. Totipotent, pluripotent or unipotent stem cells: A complex regulatory enigma and fascinating biology. J Law Med 2007; 15(2): 212-8.
Giri TK, Verma S, Alexander A, Badwaik H, Tripathy M, Tripathi DK. Crosslinked biodegradable alginate hydrogel floating beads for stomach site specific controlled delivery of metronidazole. Farmacia 2013; 61(3): 533-50.
Polejaeva I, Mitalipov S. Stem cell potency and the ability to contribute to chimeric organisms. Reproduction (Cambridge, England) 2013; 145(3): R81-8.
Balboa D, Otonkoski T. Human pluripotent stem cell based islet models for diabetes research. Best Pract Res Clin Endocrinol Metab 2015; 29(6): 899-909.
Abdelalim EM, Bonnefond A, Bennaceur-Griscelli A, Froguel P. Pluripotent stem cells as a potential tool for disease modelling and cell therapy in diabetes. Stem Cell Rev 2014; 10(3): 327-37.
Mitalipov S, Wolf D. Totipotency, pluripotency and nuclear reprogramming. Adv Biochem Eng Biotechnol 2009; 114: 185-99.
Suad A, Patrick RJF, Ernst W. Advances in reprogramming to pluripotency. Curr Stem Cell Res Ther 2015; 10(3): 193-207.
Laura F, Anna CB. Stem cell technologies based on hemangioblast technology focusing on human blood cells. Recent Pat Drug Deliv Formul 2013; 7(1): 4-8.
Seale P, Asakura A, Rudnicki MA. The potential of muscle stem cells. Dev Cell 2001; 1(3): 333-42.
Seita J, Weissman IL. Hematopoietic stem cell: Self-renewal versus differentiation. Wiley Interdiscip Rev Syst Biol Med 2010; 2(6): 640-53.
Bruin JE, Saber N, Braun N, et al. Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs. Stem Cell Reports 2015; 4(4): 605-20.
Agrawal M, Alexander A, Khan J, et al. Recent biomedical applications on stem cell therapy: A brief overview. Curr Stem Cell Res The 2018.
Ozawa M, Sakatani M, Yao J, et al. Global gene expression of the inner cell mass and trophectoderm of the bovine blastocyst. BMC Dev Biol 2012; 12: 33.
Vazin T, Freed WJ. Human embryonic stem cells: derivation, culture, and differentiation: A review. Restor Neurol Neurosci 2010; 28(4): 589-603.
Hebrok M. Generating beta cells from stem cells-the story so far. Cold Spring Harb Perspect Med 2012; 2(6): a007674.
da Silva CL, Goncalves R, Porada CD, et al. Differences amid bone marrow and cord blood hematopoietic stem/progenitor cell division kinetics. J Cell Physiol 2009; 220(1): 102-11.
Ballard VL. Stem cells for heart failure in the aging heart. Heart Fail Rev 2010; 15(5): 447-56.
Zhou C, Grottkau BE, Zou S. Regulators of stem cells proliferation in tissue regeneration. Curr Stem Cell Rep 2016; 11(3): 177-87.
Visvader JE, Clevers H. Tissue-specific designs of stem cell hierarchies. Nat Cell Biol 2016; 18(4): 349-55.
Brack AS, Rando TA. Tissue-specific stem cells: Lessons from the skeletal muscle satellite cell. Cell Stem Cell 2012; 10(5): 504-14.
Saraf S, Gupta A, Alexander A, Khan J, Jangde M, Saraf S. Advancements and avenues in nanophytomedicines for better pharmacological responses. J Nanosci Nanotechnol 2015; 15(6): 4070-9.
Viswanathan C, Kulkarni R, Bopardikar A, Ramdasi S. Significance of CD34 negative hematopoietic stem cells and cd34 positive mesenchymal stem cells - a valuable dimension to the current understanding. Curr Stem Cell Rep 2017; 12(6): 476-83.
Tsolaki E, Yannaki E. Stem cell-based regenerative opportunities for the liver: State of the art and beyond. World J Gastroenterol 2015; 21(43): 12334-50.
Bergstrom T, Forsberg-Nilsson K. Neural stem cells: brain building blocks and beyond. Ups J Med Sci 2012; 117(2): 132-42.
Li Z, Leung M, Hopper R, Ellenbogen R, Zhang M. Feeder-free self-renewal of human embryonic stem cells in 3D porous natural polymer scaffolds. Biomaterials 2010; 31(3): 404-12.
Ji L, Liu YX, Yang C, et al. Self-renewal and pluripotency is maintained in human embryonic stem cells by co-culture with human fetal liver stromal cells expressing hypoxia inducible factor 1alpha. J Cell Physiol 2009; 221(1): 54-66.
Loeser RF. Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med 2010; 26(3): 371-86.
Joseph R, Srivastava OP, Pfister RR. Modeling keratoconus using induced pluripotent stem cells. Invest Ophthalmol Vis Sci 2016; 57(8): 3685-97.
Sun C, Wilson GS, Fan JG, Qiao L. Potential applications of induced pluripotent stem cells (iPSCs) in hepatology research. Curr Stem Cell Res Ther 2015; 10(3): 208-15.
Soejitno A, Prayudi PK. The prospect of induced pluripotent stem cells for diabetes mellitus treatment. Ther Adv Endocrinol Metab 2011; 2(5): 197-210.
Mortada I, Bilani N. Advances in the production and application of induced pluripotent stem cells. Curr Stem Cell Res Ther 2017; 12(8): 637-43.
Pal R, Mariappan I, Velayudhan SR. Editorial: Induced pluripotent stem cell-derived mesenchymal stem cells: ushering of a new era in personalized cell therapies. Curr Stem Cell Res Ther 2016; 11(2): 97-8.
Hosokawa Y, Toyoda T, Fukui K, et al. Insulin-producing cells derived from ‘induced pluripotent stem cells’ of patients with fulminant type 1 diabetes: Vulnerability to cytokine insults and increased expression of apoptosis-related genes. J Diabetes Investig 2017. [Epub ahead of print].
Stepniewski J, Kachamakova-Trojanowska N, Ogrocki D, et al. Induced pluripotent stem cells as a model for diabetes investigation. Sci Rep 2015; 5: 8597.
Marraffini LA. CRISPR-Cas immunity in prokaryotes. Nature 2015; 526: 55.
Lee KO, Gan SU, Calne RY. Stem cell therapy for diabetes. Indian J Endocrinol Metab 2012; 16(Suppl. 2): S227-9.
Shruti D. Extrinsic factors promoting insulin producing cell-differentiation and insulin expression enhancement-hope for diabetics. Curr Stem Cell Res Ther 2013; 8(6): 471-83.
Song Cheol K, Duck Jong H, Ji Yeon L. Adipose Tissue Derived Stem Cells for Regeneration and Differentiation into Insulin-Producing Cells. Curr Stem Cell Res Ther 2010; 5(2): 190-4.
Carlos Eduardo Barra C, Julio Cesar V. Stem Cell-Based therapies and immunomodulatory approaches in newly diagnosed type 1 diabetes. Curr Stem Cell Res Ther 2011; 6(1): 10-5.
Kim SC, Han DJ, Lee JY. Adipose tissue derived stem cells for regeneration and differentiation into insulin-producing cells. Curr Stem Cell Res Ther 2010; 5(2): 190-4.
El-Demerdash RF, Hammad LN, Kamal MM, El Mesallamy HO. A comparison of Wharton’s jelly and cord blood as a source of mesenchymal stem cells for diabetes cell therapy. Regen Med 2015; 10(7): 841-55.
Ke Y, Shane F, Xiangwei X. Beta cell regeneration in adult mice: Controversy over the involvement of stem cells. Curr Stem Cell Res Ther 2016; 11(7): 542-6.
Aaron CT, Utpal S, Paras KM. Synergy of microRNA and stem cell: A novel therapeutic approach for diabetes mellitus and cardiovascular diseases. Curr Diabetes Rev 2011; 7(6): 367-76.
Samuel AL, Joia S, Josef K. Hematopoietic stem cell transplantation for the treatment of autoimmunity in type 1 diabetes. Curr Stem Cell Res Ther 2011; 6(1): 29-37.
Bruin JESN, Braun N, Fox JK, Mojibian M, Asadi A. Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs. Stem Cell Reports 2015; 4(4): 605-20.
Li M, Li H, Ruan Y, Wang T, Liu J. Stem cell therapy for diabetic erectile dysfunction in rats: A meta-analysis. PLoS One 2016; 11(4): e0154341.
Shukla P, Singh A, Gawri S, Alexander A, Sonwane S. In vitro propagation of Barleria prionitis Linn and its antibacterial activity. IJPPR 2011; 2(1): 170-2.
Rezania A, Bruin JE, Arora P, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol 2014; 32(11): 1121-33.
Scoville DW, Jetten AM. Studying pancreas development and diabetes using human pluripotent stem cells. Stem Cell Investig 2016; 3: 80.
Alluru SR, Kishore K, Norman E. Human umbilical cord blood as an emerging stem cell therapy for diabetes mellitus. Curr Stem Cell Res Ther 2010; 5(4): 356-61.
Villani V, Milanesi A, Sedrakyan S, et al. Amniotic fluid stem cells prevent beta-cell injury. Cytotherapy 2014; 16(1): 41-55.
Bhartiya D. Stem cells to replace or regenerate the diabetic pancreas: Huge potential & existing hurdles. Indian J Med Res 2016; 143(3): 267-74.
Zhao Y, Jiang Z, Zhao T, et al. Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: Phase I/II clinical trial. BMC Med 2013; 11: 160.
Weiskopf K, Schnorr PJ, Pang WW, et al. Myeloid cell origins, differentiation, and clinical implications. Microbiol Spectr 2016; 4(5)
Vrtovec B, Sever M, Jensterle M, et al. Efficacy of CD34+ stem cell therapy in nonischemic dilated cardiomyopathy is absent in patients with diabetes but preserved in patients with insulin resistance. Stem Cells Transl Med 2016; 5(5): 632-8.
Bervar M, Kozelj M, Poglajen G, et al. Effects of transendocardial CD34(+) cell transplantation on diastolic parameters in patients with nonischemic dilated cardiomyopathy. Stem Cells Transl Med 2017; 6(6): 1515-21.
Fadini GP, Fiala M, Cappellari R, et al. Diabetes limits stem cell mobilization following G-CSF but not plerixafor. Diabetes 2015; 64(8): 2969-77.
Delgado E, Perez-Basterrechea M, Suarez-Alvarez B, et al. Modulation of autoimmune T-cell memory by stem cell educator therapy: Phase 1/2 clinical trial. EBioMedicine 2015; 2(12): 2024-36.
Schulz TC. Concise Review: Manufacturing of pancreatic endoderm cells for clinical trials in type 1 diabetes. Stem Cells Transl Med 2015; 4(8): 927-31.
Trounson A, McDonald C. Stem cell therapies in clinical trials: Progress and challenges. Cell Stem Cell 2015; 17(1): 11-22.

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Year: 2019
Page: [146 - 151]
Pages: 6
DOI: 10.2174/1574888X13666181002154110
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