Login Register Cart 0
Generic placeholder image

Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Effects of Mesenchymal Stem Cell-conditioned Media with Natural Immunomodulatory Agent Resveratrol on Type 1 Diabetes

In Press, (this is not the final "Version of Record"). Available online 08 March, 2024
Author(s): Krushna Abhale*, Veeranjaneyulu Addepalli*, Shivani Desai, Avinash Sanap and Ramesh Bhonde
Published on: 08 March, 2024

Article ID: e080324227818

DOI: 10.2174/0115701638276524240305054259

Price: $95

Abstract

Background: Type 1 diabetes mellitus (T1DM) is a condition marked by elevated blood sugar levels and primarily recognized by the destruction of beta cells caused by an autoimmune attack, which is a significant characteristic of T1DM. Recent studies have demonstrated the regenerative potential of conditioned medium therapy. In light of this, the current research sought to assess the impact of Mesenchymal Stem Cell conditioned media (CM) and CM with resveratrol (CM+ Resveratrol) on the management of T1DM in Swiss albino mice. By leveraging and modifying existing conditioned medium therapy, this study aims to evaluate its effectiveness in treating T1DM.

Materials & Methods: Diabetes was induced in animals using the diabetes-inducing agent streptozotocin (STZ). The animals were then divided into five groups: Normal control, Disease Control, Resveratrol, Condition Media, and CM + Resveratrol. Treatments were given to the animals accordingly. The study period was 28 days. During this time, the animals were monitored for foodwater intake twice a week, blood glucose levels, and body weight. At the conclusion of the 28-day study period, biochemical estimations were performed for serum insulin levels, C-peptide levels, anti-inflammatory cytokines levels and pro-inflammatory cytokines levels. Additionally, histopathology of the pancreas was performed.

Results: The test groups showed a significant decrease in blood glucose levels, an increase in Cpeptide levels, and a decrease in pro-inflammatory cytokine levels compared to the disease group. However, no statistically significant change within groups was observed in terms of serum insulin and anti-inflammatory cytokine levels. The improvement in diabetic symptoms, such as polyphagia, polydipsia, and weight loss, was observed in the treatment group, along with pancreatic regeneration, which indicated improved insulin secretion.

Conclusion: In the current investigation, we concluded that CM and CM+ Resveratrol, as natural immunomodulators, have the capacity to regenerate injured pancreatic beta cells and have antidiabetic action, together with immunomodulating impact. Nonetheless, future studies on this therapy appear to be promising.

[1]
Pellegrini S, Cantarelli E, Sordi V, Nano R, Piemonti L. The state of the art of islet transplantation and cell therapy in type 1 diabetes. Acta Diabetol 2016; 53(5): 683-91.
[http://dx.doi.org/10.1007/s00592-016-0847-z]
[2]
Wu H, Mahato RI. Mesenchymal stem cell-based therapy for type 1 diabetes. Discov Med 2014; 17(93): 139-43.
[3]
Yi L, Swensen AC, Qian WJ. Serum biomarkers for diagnosis and prediction of type 1 diabetes. Transl Res 2018; 201: 13-25.
[http://dx.doi.org/10.1016/j.trsl.2018.07.009]
[4]
Op de Beeck A, Eizirik DL. Viral infections in type 1 diabetes mellitus — why the β cells? Nat Rev Endocrinol 2016; 12(5): 263-73.
[http://dx.doi.org/10.1038/nrendo.2016.30]
[5]
Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 2005; 54(S2): S97-S107.
[http://dx.doi.org/10.2337/diabetes.54.suppl_2.S97]
[6]
Leung PS, Leung PS. The Renin-Angiotensin System: Current Research Progress in The Pancreas. Springer 2010.
[http://dx.doi.org/10.1007/978-90-481-9060-7_1]
[7]
In’t Veld P, Marichal M. Microscopic anatomy of the human islet of Langerhans. Adv Exp Med Biol 2010; 654: 1-19.
[http://dx.doi.org/10.1007/978-90-481-3271-3_1]
[8]
Lew M, Pang J. Exocrine glands (Salivary Gland and Pancreas). Normal Cytology: An Illustrated, Practical Guide 2023; 41-9.
[9]
Zhang J, Liu F. Tissue-specific insulin signaling in the regulation of metabolism and aging. IUBMB Life 2014; 66(7): 485-95.
[http://dx.doi.org/10.1002/iub.1293]
[10]
Gil-Rivera M, Medina-Gali RM, Martínez-Pinna J, Soriano S. Physiology of pancreatic β-cells: Ion channels and molecular mechanisms implicated in stimulus-secretion coupling. Int Rev Cell Mol Biol 2021; 359: 287-323.
[http://dx.doi.org/10.1016/bs.ircmb.2021.02.006]
[11]
Rorsman P, Ashcroft FM. Pancreatic β-cell electrical activity and insulin secretion: Of mice and men. Physiol Rev 2018; 98(1): 117-214.
[http://dx.doi.org/10.1152/physrev.00008.2017]
[12]
Fu ZR, Gilbert E, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev 2013; 9(1): 25-53.
[http://dx.doi.org/10.2174/157339913804143225]
[13]
Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet 2014; 383(9911): 69-82.
[http://dx.doi.org/10.1016/S0140-6736(13)60591-7]
[14]
Trung LQ, An DTT. Is resveratrol a cancer immunomodulatory molecule? Front Pharmacol 2018; 9: 1255.
[http://dx.doi.org/10.3389/fphar.2018.01255]
[15]
Shakoor H, Feehan J, Apostolopoulos V, et al. Immunomodulatory effects of dietary polyphenols. Nutrients 2021; 13(3): 728.
[http://dx.doi.org/10.3390/nu13030728]
[16]
Gianchecchi E, Fierabracci A. Insights on the effects of resveratrol and some of its derivatives in cancer and autoimmunity: A molecule with a dual activity. Antioxidants 2020; 9(2): 91.
[http://dx.doi.org/10.3390/antiox9020091]
[17]
Zhang LX, Li CX, Kakar MU, et al. Resveratrol (RV): A pharmacological review and call for further research. Biomed Pharmacother 2021; 143: 112164.
[http://dx.doi.org/10.1016/j.biopha.2021.112164]
[18]
Hoca M, Becer E, Vatansever HS. The role of resveratrol in diabetes and obesity associated with insulin resistance. Arch Physiol Biochem 2021; 129(2): 555-61.
[19]
Maqsood M, Kang M, Wu X, Chen J, Teng L, Qiu L. Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine. Life Sci 2020; 256: 118002.
[http://dx.doi.org/10.1016/j.lfs.2020.118002]
[20]
Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: Amazing remedies for bone and cartilage defects. Stem Cell Res Ther 2020; 11(1): 492.
[http://dx.doi.org/10.1186/s13287-020-02001-1]
[21]
Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential. Trends Pharmacol Sci 2020; 41(9): 653-64.
[http://dx.doi.org/10.1016/j.tips.2020.06.009]
[22]
Galipeau J, Sensébé L. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell 2018; 22(6): 824-33.
[http://dx.doi.org/10.1016/j.stem.2018.05.004]
[23]
Krampera M, Le Blanc K. Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy. Cell Stem Cell 2021; 28(10): 1708-25.
[http://dx.doi.org/10.1016/j.stem.2021.09.006]
[24]
Ilonen J, Lempainen J, Veijola R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol 2019; 15(11): 635-50.
[http://dx.doi.org/10.1038/s41574-019-0254-y]
[25]
Warshauer JT, Bluestone JA, Anderson MS. New frontiers in the treatment of type 1 diabetes. Cell Metab 2020; 31(1): 46-61.
[http://dx.doi.org/10.1016/j.cmet.2019.11.017]
[26]
Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc 2021; 1(4): e78.
[http://dx.doi.org/10.1002/cpz1.78]
[27]
Lee SM, Yang H, Tartar DM, et al. Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes. Diabetologia 2011; 54(5): 1136-46.
[http://dx.doi.org/10.1007/s00125-011-2064-1]
[28]
Roep BO, Thomaidou S, van Tienhoven R, Zaldumbide A. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?). Nat Rev Endocrinol 2021; 17(3): 150-61.
[http://dx.doi.org/10.1038/s41574-020-00443-4]
[29]
Faist E, Schinkel C, Zimmer S. Update on the mechanisms of immune suppression of injury and immune modulation. World J Surg 1996; 20(4): 454-9.
[http://dx.doi.org/10.1007/s002689900071]
[30]
Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S. Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab 2017; 6(9): 943-57.
[http://dx.doi.org/10.1016/j.molmet.2017.06.019]
[31]
Chung L, Maestas DR Jr, Housseau F, Elisseeff JH. Key players in the immune response to biomaterial scaffolds for regenerative medicine. Adv Drug Deliv Rev 2017; 114: 184-92.
[http://dx.doi.org/10.1016/j.addr.2017.07.006]
[32]
Northrup L, Christopher MA, Sullivan BP, Berkland C. Combining antigen and immunomodulators: Emerging trends in antigen-specific immunotherapy for autoimmunity. Adv Drug Deliv Rev 2016; 98: 86-98.
[http://dx.doi.org/10.1016/j.addr.2015.10.020]
[33]
Thacker EL. Immunomodulators, immunostimulants, and immunotherapies in small animal veterinary medicine. Vet Clin North Am Small Anim Pract 2010; 40(3): 473-83.
[http://dx.doi.org/10.1016/j.cvsm.2010.01.004]
[34]
Oliveira AL, Monteiro VV, Navegantes-Lima KC, et al. Natural immunomodulators role in autoimmune disease—a mini-review. Nutrients 2017; 9(12): 1306.
[http://dx.doi.org/10.3390/nu9121306]
[35]
Apaya MK, Kuo TF, Yang MT, et al. Phytochemicals as modulators of β-cells and immunity for the therapy of type 1 diabetes: Recent discoveries in pharmacological mechanisms and clinical potential. Pharmacol Res 2020; 156: 104754.
[http://dx.doi.org/10.1016/j.phrs.2020.104754]
[36]
Sorrenti V, Benedetti F, Buriani A, et al. Immunomodulatory and antiaging mechanisms of resveratrol, rapamycin, and metformin: Focus on mTOR and AMPK signaling networks. Pharmaceuticals 2022; 15(8): 912.
[http://dx.doi.org/10.3390/ph15080912]
[37]
Ali SA, Singh G, Datusalia AK. Potential therapeutic applications of phytoconstituents as immunomodulators: Pre‐clinical and clinical evidences. Phytother Res 2021; 35(7): 3702-31.
[http://dx.doi.org/10.1002/ptr.7068]
[38]
Kasahara N, Teratani T, Doi J, et al. Use of mesenchymal stem cell-conditioned medium to activate islets in preservation solution. Cell Med 2013; 5(2-3): 75-81.
[http://dx.doi.org/10.3727/215517913X666477]
[39]
Jayasinghe M, Prathiraja O, Perera PB, et al. The role of mesenchymal stem cells in the treatment of type 1 diabetes. Cureus 2022; 14(7)
[http://dx.doi.org/10.7759/cureus.27337]
[40]
Makino E, Nakamura N, Miyabe M, et al. Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti-inflammatory, neuroprotective and angiogenic actions: Cell-free regenerative medicine for diabetic polyneuropathy. J Diabetes Investig 2019; 10(5): 1199-208.
[http://dx.doi.org/10.1111/jdi.13045]
[41]
Yuan Y, Shi M, Li L, et al. Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1α pathway. Clin Sci 2016; 130(23): 2181-98.
[http://dx.doi.org/10.1042/CS20160235]
[42]
Sanap A, Bhonde R, Joshi K. Mesenchymal stem cell conditioned medium ameliorates diabetic serum-induced insulin resistance in 3T3-L1 cells. Chronic Dis Transl Med 2021; 7(01): 47-56.
[43]
Moudgil KD, Venkatesha SH. The anti-inflammatory and immunomodulatory activities of natural products to control autoimmune inflammation. Int J Mol Sci 2022; 24(1): 95.
[http://dx.doi.org/10.3390/ijms24010095]
[44]
Shnayder NA, Ashhotov AV, Trefilova VV, et al. Cytokine imbalance as a biomarker of intervertebral disk degeneration. Int J Mol Sci 2023; 24(3): 2360.
[http://dx.doi.org/10.3390/ijms24032360]
[45]
Shree N, Bhonde RR. Conditioned media from adipose tissue derived mesenchymal stem cells reverse insulin resistance in cellular models. J Cell Biochem 2017; 118(8): 2037-43.
[http://dx.doi.org/10.1002/jcb.25777]
[46]
Masithoh DB, Fibrianto YH, Anggita M, Nugroho WS, Budipitojo T. PCS-11 mesenchymal stem cell-conditioned medium improve the recovery of pancreatic α and β cells in type 1 diabetes mellitus. Hemera Zoa 2018.

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy