Differentiation of Wharton's Jelly Derived Mesenchymal Stem Cells into Insulin Producing Cells
-
Hossein Ranjbaran
,
Saeid Abediankenari
,
Alireza Khalilian
,
Zahra Rahmani
,
Marzei Momeninezhad Amiri
,
Zahra Hosseini Khah
Abstract
Background: Diabetes caused by insulin production disturbance is considered as the most common metabolic disorder all over the world. Diabetes may outbreak because of low insulin secretion by Islets of Langerhans β-cells, insulin resistance or both of them. In this way, using stem cells, which have the capability to differentiate into Pancreatic β-cells, is one of novel methods in this field. MSCs are the most important candidates for cellular therapy.
Materials and Methods: Insulin level was examined using ELIZA method. In order to examine the morphology of differentiated cells, they were stained by Dithizone. Insulin-producer cells are cells which turn into red as a result of staining. Specific gene involving insulin-producing cells was evaluated by Real Time-PCR method.
Results: The ELISA results showed that the treated cells secreted more insulin than the control group. Moreover, we found differentiation of MSCs toward insulin-secreting cells. In order to evaluate insulin production in clusters on day 21 of differentiation, we used dithizone (DTZ) staining. PDX-1 gene was confirmed by RT- PCR analysis.
Conclusion: In this study, we differentiated MSCs into insulin-producing cells in vitro. It is concluded that MSCs may be considered as an excellent candidate in β-cell therapy in diabetes patients.
American Diabetes Association. Diagnosis and classification of diabetes mellitus .Diabetes Care. 2010; 33(Suppl 1):S62-S69.
-Abu-Rmeileh NM, Husseini A, Capewell S, et al. Preventing type 2 diabetes among Palestinians: comparing five future policy scenarios. BMJ open. 2013; 3(12):e003558.
Abediankenari S, Eslami MB, Sarrafnejad A, et al. Dendritic cells bearing HLA-G inhibit T-Cell activation in type 1 diabetes. Allergy Asthma. Immunol. 2007 6(1): 1-7.
Abediankenari S, Ghasemi M. Generation of immune inhibitory dendritic cells and CD4+T regulatory cells inducing by TGF-beta.Iran J Allergy Asthma Immunol. 2009 8(1):p.25-30.
Li G, Abediankenari S, Kim YJ, et al. TGF-beta combined with M-CSF and IL-4 induces generation of immune inhibitory cord blood dendritic cells capable of enhancing cytokine-induced ex vivo xpansion of myeloid progenitors. Blood. 2007. 110(8): 2872-9.
Tang DQ, Cao LZ, Burkhardt BR, et al. In vivo and in vitro characterization of insulin- producing cells obtained from murine bone marrow.Diabetes. 2004; 53(7):1721-32.
Gnecchi M, He H, Liang OD, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature Med. 2005; 11(4):367–80.
Schuleri KH, Feigenbaum GS, Centola M, et al. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischemic cardiomyopathy. Eur Heart J. 2009; 30(22):2722–32.
Hatzistergos KE, Quevedo H, Oskouei BN, et al. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res. 2010; 107(7):913–22.
Amado LC, Schuleri KH, Saliaris AP, et al. Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol. 2006; 48(10):2116–24.
Karantalis V, DiFede DL, Gerstenblith G, et al. Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: the prospective randomized study of mesenchymal stem cell therapy in patients undergoing cardiac surgery (PROMETHEUS) trial. Circ Res. 2014; 114(8):1302–10.
Heldman AW, DiFede DL, Fishman JE, et al. Tran’s endocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 2014; 311(1):62–73.
Hare JM, Traverse JH, Henry TD, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009; 54(24):2277–86.
Hare JM, DiFede DL, Castellanos AM, et al. Randomized Comparison of Allogeneic Vs. Autologous Mesenchymal Stem Cells for Non-ischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017; 69(5):526–37.
Watt FM, Hogan BL. Out of Eden: stem cells and their niches. Science. 2000; 287(5457):1427-30.
Becker AJ, McCuloch EA, Tili JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells .Nature. 1963; 197:452-4.
Mishra PJ, Mishra PJ, Glod JW, et al. Mesenchymal stem cell: flip side of the coin. Cancer Res. 2009; 69(4):1255-8.
Vaca P, Martin F, Vegara-Meseguer JM, et al.Induction of differentiation of embryonic stem cells into insulin-secreting cells by fetal soluble factors. Stem cells. 2006; 24(2):258-65.
Mafi R, Hindocha S, Mafi P, et al. Sources of adult mesenchymal stem cells applicable for musculoskeletal applications-a systematic review of the literature. Open Orthop J. 2011; 5Suppl 2:242-8.
Lee OK , Kuo TK, Chen WM , et al. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2004; 103(5):1669-75.
Vater C, Kasten P, Stiehler M. Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater. 20011; 7(2):463-77.
Lumelsky N, Blondel O, Laeng P, et al., Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science. 2001; 292 (5520): 1389-94.
Kim SK, Hebrok M, Melton DA. Melton,Notochord to endoderm signaling is required for pancreas development. Development. 1997; 124(21): 4243-52.
Schwitzgebel VM, Scheel DW, Conners JR, et al. Expression of neurogenin3 reveal an islet cell precursor population in the pancreas. Development. 2000; 127(16): 3533-42.
Miyazaki S, Yamato E, Miyazaki J. Regulated expression of PDX-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. Diabetes. 2004; 53(4): 1030-7.
Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein.Cell.1990; 60(4): 585-95.
Zulewski H, Abraham EJ, Gerlach MJ, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiation ex vivo into pancreatic endocrine, and hepatic phenotypes. Diabetes. 2001; 50(3): 521-33.
Crossley JA, Jennifer A, Berry E, et al. Insulin-dependent diabetes mellitus and prenatal screening results: current experience from a regional screening programme. Prenatal Diagnosis.1996; 16(11): 1039-42.
Abraham EJ, Leech CA, Lin JC, et al. Insulintropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producin cells. Endocrinology. 2002; 143(8):3152-61.
Selander L, Edlund H. Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev. 2002; 113(2): 189-92.
Treutelaar MK, Skidmore JM, Dias-Leme CL, et al. Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet. Diabetes. 2003; 52(10): 2503-12.
Humphrey RK, Bucay N, Beattie GM, et al. Characterization and isolation of promoter-defined nestin-positive cells from the human fetal pancreas. Diabetes. 2003; 52(10): 2519-25.
Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002; 418(6893): 41–9.
Chandra V, G S, Phadnis S, Nair PD, et al. Generation
of pancreatic hormone-expressing islet-like cell aggregates from murine adipose tissue derived stem cells. Stem Cells. 2009; 27(8): 1941–53.
Aguayo-Mazzucato C, Bonner-Weir S. Stem Cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol.2010; 6(3):139-48.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T) Method. Methods. 2001; 25(4): 402–8.
Shiroi A, Yoshikawa M, Yokota H, et al. Identification of insulin-producing cells derived from embryonic stem cells by zinc-chelating dithizone. Stem cells. 2002; 20(4):284-92.
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284(5411). 143–7.
Govindasamy V, Ronald VS, Abdullah AN, et al. Differentiation of dental pulp stem cells into islet-like aggregates. J Dent Res. 2011; 90(5):646-52.
Koblas T, Zacharovová K, Berková Z, et al. In vivo differentiation of human umbilical cord blood-derived cells into insulin-producing beta cells. Folia Biol (Praha). 2009; 55(6):224-32.
Tang DQ, Cao LZ, Burkhardt BR, et al. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes. 2004; 53(7):1721-32.
Yang LJ. Liver stem cell-derived beta-cell surrogates for treatment of type 1 diabetes. Autoimmun Rev. 2006; 5(6):409-13.
Tang DQ, Lu S, Sun YP, et al. Reprogramming liver-stem WB cells into functional insulin-producing cells by persistent expression of Pdx1- and Pdx1-VP16 mediated by lentiviral vectors. Lab Invest. 2006. 86 (1) 83–93.
Gao F, Wu DQ, Hu YH, et al. In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells. Transl Res. 2008; 151(6):293–302.
Chandra V, Swetha G, Muthyala S, et al. Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice. PLoS ONE. 2011; 6(6):e20615.
Zhang N, Li J, Luo R, et al. Bone marrow mesenchymal stem cells induce angiogenesis and attenuate the remodeling of diabetic cardiomyopathy. Exp Clin Endocrinal Diabetes. 2008; 116(2):104–11.
Yang Z, Li K, Yan X, et al. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes Arch Clin Exp Ophthalmol. 2010; 248(10):1415-22.
Shibata T, Naruse K, Kamiya H, et al. Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes. 2008; 57(11):3099–3107.
Ezquer FE, Ezquer ME, Parrau DB, et al. Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice. Biol Blood Marrow Transpl. 2008; 14(6):631–40.
Wu Y, Chen L, Scott PG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007; 25(10):2648–59.
Kuo, CY, Lin CH. Stem cell therapy: differentiation potential of insulin producing cells from human adipose derived stem cells and umbilical cord MSCs. International Journal of Clinical Medicine Research. 2014; 1(1): 21–25.
Tuan RS, Boland G, Tuli R. Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther. 2003; 5(1):32-45.
Domínguez-Bendala J, Lanzoni G, Inverardi L, et al. Concise review: mesenchymal stem cells for diabetes. Stem Cells Transl Med. 2012; 1(1):59-63.
Rahmati S, Alijani N, Kadivar M. In vitro generation of glucose-responsive insulin producing cells using lentiviral based PDX-1 gene transduction of mouse (C57BL/6) mesenchymal stem cells. Biochem Biophys Res Commun. 2013; 437(3):413-9.
Sipione S, Eshpeter A, Lyon JG. Insulin expressing cells from differentiated embryonic stem cells are not beta cells.Diabetologia.2004; 47(3): 499-508.
Hansson M, Tonning A, Frandsen U, et al. Artifactual insulin release from differentiated embryonic stem cells. Diabetes. 2004; 53(10): 2603-9.
Rajagopal J, Anderson WJ, Kume S, et al. Insulin staining of ES cell progeny from insulin uptake.Science.2003;299(5605): 363.
D'Amour KA, Bang AG, Eliazer S, et al. Production of pancreatic hormone – expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006; 24(11): 1392 –401.
Shim JH, Kim SE, Woo DH, et al. Directed differentiation of human embryonic stem cells towards pancreatic cell fate.Diabetologia.2007; 50(6): 1228 – 38.
Hu YH, Wu DQ, Gao F, et al. Notch signaling : a novel regulating differentiation mechanism of human umbilical cord blood – derived mesenchymal stem cells into insulin _producing cells in vitro. Chin Med J (Engl).2010; 123(5):606 – 14.
Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010; 6(3):139 – 48.
| Files | ||
| Issue | Vol 12, No 3 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Mesenchymal stem cells Wharton`s jelly Differentiation Insulin producing cells | ||
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