Mesenchymal stem cells that located in the electromagnetic fields improves rat model of Parkinson's disease

Document Type: Original Article

Authors

1 Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

2 Research Center of Nervous System Stem Cells, Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

3 Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

4 Department of Anatomy, School of Medicine, AJA Medical University, Tehran, Iran

Abstract

Objective(s): The main characteristic of mesenchymal stem cells (MSCs) is their ability to produce other cell types. Electromagnetic field (EMF) stimulates differentiation of MSCs into other cells. In this study, we investigated whether EMF can effect on the differentiation of MSCs into dopaminergic (DA) neurons.
Materials and Methods: An EMF with a frequency of 50 Hz and two intensities of 40 and 400 µT 1hr/day was generated around the cells for a week. Afterwards, these cells were injected into the left ventricle of Parkinsonian rats. The rats survived for 2 weeks, and then sampling was performed.
Results: The injected cells differentiated into DA neurons and sporadically settled in the substantia nigra pars compacta (SNpc). Transplanted rats exhibited significant partial correction apomorphine-induced rotational behavior compared to Parkinsonian rats (5.0±0.1 vs 7.57±0.08). Results demonstrated that endogenous serum and brain derived neurotrophic factor (BDNF) were altered in all experimental groups. The greatest increase was in group of 400 µT EMF in comparison with Parkinsonian rats (398±15 vs. 312±11.79 pg ⁄ mg). Current study have shown that 6-Hydroxydopamine can cause severe loss of dopaminergic neurons (68±6.58), but injected MSCs that exposed to 40 and 400 µT EMF increased dopaminergic neurons in SNpc ( 108±2.33  & 126±3.89) (P<0.001).
Conclusion: Electromagnetic fields with particular frequencies stimulate MSCs. So, these cells had anti-Parkinsonian properties in our studies.

Keywords


1. Chen CC, Shih YY, Chang C. Dopaminergic imaging of nonmotor manifestations in a rat model of Parkinson's disease by fMRI. Neurobiol Dis 2013; 49:99-106.

2. Danielyan L, Beer-Hammer S, Stolzing A, Schäfer R, Siegel G, Fabian C, et al. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease. Cell Transplant 2014; 1:123-139.

3. Lin YC, Hsieh AR, Hsiao CL, Wu SJ, Wang HM, Lian IeB, et al. Identifying rare and common disease asso-ciated variants in genomic data using Parkinson's disease as a model. J Biomed Sci 2014; 21:88.

4. Capitelli CS, Lopes CS, Alves AC, Barbiero J, Oliveira LF, da Silva VJ, et al. Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson'sdisease: a comparison study of mononuclear and mesenchymal stem cells. Int J Med Sci 2014; 11:1049-1064.

5. Glavaski-Joksimovic A, Bohn MC. Mesenchymal stem cells and neurodegeneration in Parkinson's  disease. Exp Neurol 2013; 247:25-38.

6. Wang Y, Yang J, Li H, Wang X, Zhu L, Fan M, et al. Hypoxia promotes dopaminergic differentiation of mesenchymal stem cells and shows benefits for transplantation in a rat model of Parkinson's disease. PLoS One 2013; 8:54296.

7. Khan MS, Tabrez S, Priyadarshini M, Priyamvada S, Khan MM. Targeting Parkinson's-tyrosine hydroxyl-lase and oxidative stress as points of interventions. CNS Neurol Disord Drug Targets 2012; 11:369-380.

8. Shukla A, Mohapatra TM, Parmar D, Seth K. Neuroprotective potentials of neurotrophin rich olfactory ensheathing cell's conditioned media against 6OHDA-induced oxidative damage. Free Radic Res 2014; 48:560-571.

9. Golbach LA, Scheer MH, Cuppen JJ, Savelkoul H, Verburg-van Kemenade BM. Low-frequency electromagnetic field exposure enhances extra-cellular trap formation by human neutrophils through the NADPH Pathway. J Innate Immun 2015; 7:459-465.

10. Amaroli A, Chessa MG, Bavestrello G, Bianco B. Effects of an extremely low-frequency electro-magnetic field on stress factors: a study in Dictyostelium discoideum cells. Eur J Protistol 2013; 49:400-405.

11. Ketabi N, Mobasheri H, Faraji-Dana R. Electromagnetic fields (UHF) increase voltage sensitivity of membrane ion channels; possible indication of cell phone effect on living cells. Electromagn Biol Med 2015; 34:1-313.

12. Kim HJ, Jung J, Park JH, Kim JH, Ko KN, Kim CW. Extremely low-frequency electromagnetic fields induce neural differentiation in bone marrow derived mesenchymal stem cells. Exp Biol Med (Maywood) 2013; 238:923-931.

13. Ross CL, Siriwardane M, Almeida-Porada G, Porada CD, Brink P, Christ GJ, et al. The effect of low-frequency electromagnetic field on human bone marrow stem/progenitor cell differentiation. Stem Cell Res 2015; 15:96-108.

14. Safari M, Jadidi M, Baghian A, Hasanzadeh H. Proliferation and differentiation of rat bone marrow stem cells by 400  µT electromagnetic field. Neurosci Lett 2015; 612:1-6.

15. Datta I, Bhonde R. Can mesenchymal stem cells reduce vulnerability of dopaminergic neurons in the substantia nigra to oxidative insult in individuals at risk to Parkinson's disease? Cell Biol Int 2012; 36:617-624.

16. García Santos JM, Blanquer M, Torres del Río S, Iniesta F, Espuch JG, Pérez-Espejo MA, et al. Acute and chronic MRI changes in the spine and spinal cord after surgical stem cell grafting in patients with definite amyotrophic lateral sclerosis: post-infusion injuries are unrelated with clinical impairment. Magn Reson Imaging 2013; 31:1298-1308.

17. Poniedzialek B, Rzymski P, Nawrocka-Bogusz H, Jaroszyk F, Wiktorowicz K. The effect of electromagnetic field on reactive oxygen species production in human neutrophils in vitro. Electromagn Biol Med 2013; 32:333-341.

18. Zhang M, Li X, Bai L, Uchida K, Bai W, Wu B, et al. Effects of low frequency electromagnetic field on proliferation of human epidermal stem cells: An in vitro study. Bioelectromagnetics 2013; 34:74-80.

19. Zhong C, Zhang X, Xu Z, He R. Effects of low-intensity electromagnetic fields on the proliferation and differentiation of cultured mouse bone marrow stromal cells. Phys Ther 2012; 92:1208-1219. 

20. Eleuteri AM, Amici M, Bonfili L, Cecarini V, Cuccioloni M, Grimaldi S, et al. 50 Hz extremely low frequency electromagnetic fields enhance protein carbonyl groups content in cancer cells: effects on proteasomal systems. J Biomed Biotechnol  2009; 2009: 834239.

21. Pall ML. Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J Cell Mol Med 2013; 17:958-965.

22. Luo FL, Yang N, He C, Li HL, Li C, Chen F, et al. Exposure to extremely low frequency electromagnetic fields alters the calcium dynamics of cultured entorhinal cortex neurons. Environ Res 2014; 135:236-246.

23. Platano D, Mesirca P, Paffi A, Pellegrino M, Liberti M, Apollonio F, et al. Acute exposure to low-level CW and GSM-modulated 900 MHz radiofrequency does not affect Ba 2+ currents through voltage-gated calcium channels in rat cortical neurons. Bioelectromagnetics 2007; 28:599-607.

24. Ge W, Ren C, Duan X, Geng D, Zhang C, Liu X, et al. Differentiation of mesenchymal stem cells into neural stem cells using cerebrospinal fluid. Cell Biochem Biophys 2015; 71:449-455.

25. Schäfer R, Kehlbach R, Muller M, Bantleon R, Kluba T, Ayturan M, et al. Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to adecrease in migration capacity and colony formation ability. Cytotherapy 2009; 11:68-78.

26. Schäfer R, Bantleon R, Kehlbach R, Siegel G, Wiskirchen J, Wolburg, H, et al. Functional investigation on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles. BMC Cell Biol 2010; 11:22. 

27. Ventura C, Maioli M, Asara Y, Santoni D, Mesirca P, Remondini D, et al. Turning on stem cell cardiogenesis with extremely low frequency magnetic fields. FASEB J 2005; 19:155–157, 470.

28. Mascheck L, Sharifpanah F, Tsang SY, Wartenberg M, Sauer H. Stimulation of cardiomyogenesis from mouse embryonic stem cells by nuclear translocation of cardiotrophin-1. Int J Cardiol 2015; 193:23-33.

29. Wang X, Zhang H, Nie L, Xu L, Chen M, Ding Z. Myogenic differentiation and reparative activity of stromal cells derived from pericardial adipose in comparison to subcutaneous origin. Stem Cell Res Ther 2014; 5:92.

30. Ventura C, Maioli M, Asara Y, Santoni D, Mesirca P, Remondini D, et al. Turning on stem cell cardiogenesis with extremely low frequency magnetic fields. FASEB J 2004; 19:155–157.

31. Saito A, Takayama Y, Moriguchi H, Kotani K, Jimbo Y. Developmental effects of low frequency magnetic fields on P19-derived neuronal cells. Conf  Proc IEEE  Eng Med Biol Soc 2009; 2009:5942-5945.

32. Zhao W, Ma W, Zhao Z, Fang Z, Wu H. Preliminary research on the proliferation and differentiation of rat bone marrow mesenchymal stem cells with exposure to 50 Hz magnetic fields. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi  2015; 22:510-513.

33. Zhang HY, Song N, Jiang H, Bi MX, Xie JX. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor inhibit ferrous iron influx via divalent metal transporter 1 and iron regulatory protein 1 regulation in ventral mesencephalic neurons. Biochim Biophys Acta 2014; 1843:2967-2975.

34. Safari M, Sameni HR, Badban L, Bandegi AR, Vafaei AA, Rashidy Pour, et al. Protective effects of water extract of propolis on dopaminergic neurons, brain derived neurotrophic factor, and stress oxidative factors in the rat model of Parkinson’s disease. Int J Pharmacol 2015; 11:300-308.

35. Ventriglia M, Zanardini R, Bonomini C, Zanetti O, Volpe D, Pasqualetti P, et al. Serum brain-derived neurotrophic factor levels in different neurological diseases. Biomed Res Int 2013; 2013:901082.

 36. Ziebell M, Khalid U, Klein AB, Aznar S, Thomsen G, Jensen P, et al. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegene-ration. Neurobiol Aging 2012; 33:1-5.

37. Białecka M, Kurzawski M, Roszmann A, Robowski P, Sitek EJ, Honczarenko K, et al. BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson'sdisease. Neurosci Lett 2014; 561:86-90.

38. Gopalakrishna A, Alexander SA. Understan-ding Parkinson Disease: A Complex and Multifaceted Illness. J Neurosci Nurs 2015; 47:320-326.

39. Rizzo F, Riboldi G, Salani S, Nizzardo M, Simone C, Corti S, et al. Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell Mol Life Sci 2014; 71:999-1015.

40. Razgado-Hernandez LF, Espadas-Alvarez AJ, Reyna-Velazquez P, Sierra-Sanchez A, Anaya-Martinez V, Jimenez-Estrada I, et al. The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson's disease. PLoS One 2015; 10:0117391. 

41. Zhou Y, Singh AK, Hoyt RF Jr, Wang S, Yu Z, Hunt T, et al. Regulatory T cells enhance mesenchymal stem cell survival and proliferation following autologous cotransplantation in ischemic myocar-dium. J Thorac Cardiovasc Surg 2014; 148:1131-1137.

 42. Haddad R, Saldanha-Araujo F. Mechanisms of T-cell immunosuppression by mesenchymal stromal cells: what do we know so far? Biomed Res Int 2014; 2014:216806.

 43. Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, et al. Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro. Spine 2011; 36:997–1005.

44. Jager M, Hernigou P, Zilkens C, Herten M, Li X, Fischer J, et al. Cell therapy in bone healing disorders. Orthop Rev 2010; 2:79–87.

45. Croft AP, Przyborski SA. Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells. Exp Neurol 2009; 216:329–341.

46. Wilkins A, Kemp K, Ginty M, Hares K, Mallam E, Scolding N. Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem Cell Res 2009; 3:63–70.

47. Paxinos G, Franlin k. The mouse brain in stereotaxic coordinates. San Diego: Academic Press; 1997.

48. Szapacs ME, Mathews TA, Tessarollo L, Ernest Lyons W, Mamounas LA, Andrews AM. Exploring the relationship between serotonin and brainderived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression. J Neurosci Methods 2004; 140:81-92.