Skip to content
2000
Volume 22, Issue 1
  • ISSN: 1570-1638
  • E-ISSN: 1875-6220

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 food-water 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 C-peptide 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.

Loading

Article metrics loading...

/content/journals/cddt/10.2174/0115701638276524240305054259
2025-01-01
2024-11-01
Loading full text...

Full text loading...

References

  1. PellegriniS. CantarelliE. SordiV. NanoR. PiemontiL. The state of the art of islet transplantation and cell therapy in type 1 diabetes.Acta Diabetol.201653568369110.1007/s00592‑016‑0847‑z
    [Google Scholar]
  2. WuH. MahatoR.I. Mesenchymal stem cell-based therapy for type 1 diabetes.Discov. Med.20141793139143
    [Google Scholar]
  3. YiL. SwensenA.C. QianW.J. Serum biomarkers for diagnosis and prediction of type 1 diabetes.Transl. Res.2018201132510.1016/j.trsl.2018.07.009
    [Google Scholar]
  4. Op de BeeckA. EizirikD.L. Viral infections in type 1 diabetes mellitus — why the β cells?Nat. Rev. Endocrinol.201612526327310.1038/nrendo.2016.30
    [Google Scholar]
  5. CnopM. WelshN. JonasJ.C. JörnsA. LenzenS. EizirikD.L. Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities.Diabetes200554S2S97S10710.2337/diabetes.54.suppl_2.S97
    [Google Scholar]
  6. LeungPS LeungPS The Renin-Angiotensin System: Current Research Progress in The PancreasSpringer201010.1007/978‑90‑481‑9060‑7_1
    [Google Scholar]
  7. In’t VeldP MarichalM. Microscopic anatomy of the human islet of Langerhans.Adv Exp Med Biol201065411910.1007/978‑90‑481‑3271‑3_1
    [Google Scholar]
  8. LewM PangJ. Exocrine glands (Salivary Gland and Pancreas).Normal Cytology: An Illustrated, Practical GuideChampSpringer International Publishing20234149
    [Google Scholar]
  9. ZhangJ. LiuF. Tissue-specific insulin signaling in the regulation of metabolism and aging.IUBMB Life201466748549510.1002/iub.1293
    [Google Scholar]
  10. Gil-RiveraM. Medina-GaliR.M. Martínez-PinnaJ. SorianoS. Physiology of pancreatic β-cells: Ion channels and molecular mechanisms implicated in stimulus-secretion coupling.Int. Rev. Cell Mol. Biol.202135928732310.1016/bs.ircmb.2021.02.006
    [Google Scholar]
  11. RorsmanP. AshcroftF.M. Pancreatic β-cell electrical activity and insulin secretion: Of mice and men.Physiol. Rev.201898111721410.1152/physrev.00008.2017
    [Google Scholar]
  12. FuZ.R. GilbertE. LiuD. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes.Curr. Diabetes Rev.201391255310.2174/157339913804143225
    [Google Scholar]
  13. AtkinsonM.A. EisenbarthG.S. MichelsA.W. Type 1 diabetes.Lancet20143839911698210.1016/S0140‑6736(13)60591‑7
    [Google Scholar]
  14. TrungL.Q. AnD.T.T. Is resveratrol a cancer immunomodulatory molecule?Front. Pharmacol.20189125510.3389/fphar.2018.01255
    [Google Scholar]
  15. ShakoorH. FeehanJ. ApostolopoulosV. PlatatC. Al DhaheriA.S. AliH.I. IsmailL.C. BosevskiM. StojanovskaL. Immunomodulatory effects of dietary polyphenols.Nutrients202113372810.3390/nu13030728
    [Google Scholar]
  16. GianchecchiE. FierabracciA. Insights on the effects of resveratrol and some of its derivatives in cancer and autoimmunity: A molecule with a dual activity.Antioxidants2020929110.3390/antiox9020091
    [Google Scholar]
  17. ZhangL.X. LiC.X. KakarM.U. KhanM.S. WuP.F. AmirR.M. DaiD.F. NaveedM. LiQ.Y. SaeedM. ShenJ.Q. RajputS.A. LiJ-H. Resveratrol (RV): A pharmacological review and call for further research.Biomed. Pharmacother.202114311216410.1016/j.biopha.2021.112164
    [Google Scholar]
  18. HocaM. BecerE. VatanseverH.S. The role of resveratrol in diabetes and obesity associated with insulin resistance.Arch. Physiol. Biochem.20211292555561
    [Google Scholar]
  19. MaqsoodM. KangM. WuX. ChenJ. TengL. QiuL. Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine.Life Sci.202025611800210.1016/j.lfs.2020.118002
    [Google Scholar]
  20. KangariP. Talaei-KhozaniT. Razeghian-JahromiI. RazmkhahM. Mesenchymal stem cells: Amazing remedies for bone and cartilage defects.Stem Cell Res. Ther.202011149210.1186/s13287‑020‑02001‑1
    [Google Scholar]
  21. SongN. ScholtemeijerM. ShahK. Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential.Trends Pharmacol. Sci.202041965366410.1016/j.tips.2020.06.009
    [Google Scholar]
  22. GalipeauJ. SensébéL. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities.Cell Stem Cell201822682483310.1016/j.stem.2018.05.004
    [Google Scholar]
  23. KramperaM. Le BlancK. Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy.Cell Stem Cell202128101708172510.1016/j.stem.2021.09.006
    [Google Scholar]
  24. IlonenJ. LempainenJ. VeijolaR. The heterogeneous pathogenesis of type 1 diabetes mellitus.Nat. Rev. Endocrinol.2019151163565010.1038/s41574‑019‑0254‑y
    [Google Scholar]
  25. WarshauerJ.T. BluestoneJ.A. AndersonM.S. New frontiers in the treatment of type 1 diabetes.Cell Metab.2020311466110.1016/j.cmet.2019.11.017
    [Google Scholar]
  26. FurmanB.L. Streptozotocin-induced diabetic models in mice and rats.Curr. Protoc.202114e7810.1002/cpz1.78
    [Google Scholar]
  27. LeeS.M. YangH. TartarD.M. GaoB. LuoX. YeS.Q. ZaghouaniH. FangD. Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes.Diabetologia20115451136114610.1007/s00125‑011‑2064‑1
    [Google Scholar]
  28. RoepB.O. ThomaidouS. van TienhovenR. ZaldumbideA. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?).Nat. Rev. Endocrinol.202117315016110.1038/s41574‑020‑00443‑4
    [Google Scholar]
  29. FaistE. SchinkelC. ZimmerS. Update on the mechanisms of immune suppression of injury and immune modulation.World J. Surg.199620445445910.1007/s002689900071
    [Google Scholar]
  30. ChenC. CohrsC.M. StertmannJ. BozsakR. SpeierS. Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis.Mol. Metab.20176994395710.1016/j.molmet.2017.06.019
    [Google Scholar]
  31. ChungL. MaestasD.R.Jr HousseauF. ElisseeffJ.H. Key players in the immune response to biomaterial scaffolds for regenerative medicine.Adv. Drug Deliv. Rev.201711418419210.1016/j.addr.2017.07.006
    [Google Scholar]
  32. NorthrupL. ChristopherM.A. SullivanB.P. BerklandC. Combining antigen and immunomodulators: Emerging trends in antigen-specific immunotherapy for autoimmunity.Adv. Drug Deliv. Rev.201698869810.1016/j.addr.2015.10.020
    [Google Scholar]
  33. ThackerE.L. Immunomodulators, immunostimulants, and immunotherapies in small animal veterinary medicine.Vet. Clin. North Am. Small Anim. Pract.201040347348310.1016/j.cvsm.2010.01.004
    [Google Scholar]
  34. OliveiraA.L. MonteiroV.V. Navegantes-LimaK.C. ReisJ.F. GomesR.D. RodriguesD.V. GasparS.L. MonteiroM.C. Natural immunomodulators role in autoimmune disease—a mini-review.Nutrients2017912130610.3390/nu9121306
    [Google Scholar]
  35. ApayaM.K. KuoT.F. YangM.T. YangG. HsiaoC.L. ChangS.B. LinY. YangW.C. 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.202015610475410.1016/j.phrs.2020.104754
    [Google Scholar]
  36. SorrentiV. BenedettiF. BurianiA. FortinguerraS. CaudulloG. DavinelliS. ZellaD. ScapagniniG. Immunomodulatory and antiaging mechanisms of resveratrol, rapamycin, and metformin: Focus on mTOR and AMPK signaling networks.Pharmaceuticals202215891210.3390/ph15080912
    [Google Scholar]
  37. AliS.A. SinghG. DatusaliaA.K. Potential therapeutic applications of phytoconstituents as immunomodulators: Pre‐clinical and clinical evidences.Phytother. Res.20213573702373110.1002/ptr.7068
    [Google Scholar]
  38. KasaharaN. TerataniT. DoiJ. IijimaY. MaedaM. UemotoS. FujimotoY. SataN. YasudaY. KobayashiE. Use of mesenchymal stem cell-conditioned medium to activate islets in preservation solution.Cell Med.201352-3758110.3727/215517913X666477
    [Google Scholar]
  39. JayasingheM. PrathirajaO. PereraP.B. JenaR. SilvaM.S. WeerawarnaP.S.H. SinghalM. KayaniA.M.A. KarnakotiS. JainS. The role of mesenchymal stem cells in the treatment of type 1 diabetes.Cureus202214710.7759/cureus.27337
    [Google Scholar]
  40. MakinoE. NakamuraN. MiyabeM. ItoM. KanadaS. HataM. SaikiT. SangoK. KamiyaH. NakamuraJ. MiyazawaK. GotoS. MatsubaraT. NaruseK. 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.20191051199120810.1111/jdi.13045
    [Google Scholar]
  41. YuanY. ShiM. LiL. LiuJ. ChenB. ChenY. AnX. LiuS. LuoR. LongD. ZhangW. NewsholmeP. ChengJ. LuY. Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1α pathway.Clin. Sci.2016130232181219810.1042/CS20160235
    [Google Scholar]
  42. SanapA. BhondeR. JoshiK. Mesenchymal stem cell conditioned medium ameliorates diabetic serum-induced insulin resistance in 3T3-L1 cells.Chronic Dis. Transl. Med.20217014756
    [Google Scholar]
  43. MoudgilK.D. VenkateshaS.H. The anti-inflammatory and immunomodulatory activities of natural products to control autoimmune inflammation.Int. J. Mol. Sci.20222419510.3390/ijms24010095
    [Google Scholar]
  44. ShnayderN.A. AshhotovA.V. TrefilovaV.V. NurgalievZ.A. NovitskyM.A. VaimanE.E. PetrovaM.M. NasyrovaR.F. Cytokine imbalance as a biomarker of intervertebral disk degeneration.Int. J. Mol. Sci.2023243236010.3390/ijms24032360
    [Google Scholar]
  45. ShreeN. BhondeR.R. Conditioned media from adipose tissue derived mesenchymal stem cells reverse insulin resistance in cellular models.J. Cell. Biochem.201711882037204310.1002/jcb.25777
    [Google Scholar]
  46. MasithohDB FibriantoYH AnggitaM NugrohoWS BudipitojoT PCS-11 mesenchymal stem cell-conditioned medium improve the recovery of pancreatic α and β cells in type 1 diabetes mellitus.Hemera Zoa2018
    [Google Scholar]
/content/journals/cddt/10.2174/0115701638276524240305054259
Loading
/content/journals/cddt/10.2174/0115701638276524240305054259
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test