Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica

Yang,Chunsheng; Yang,Yang; Ma,Li; Zhang,Guang‑Xian; Shi,Fu‑Dong; Yan,Yaping; Chang,Guoqiang

doi:10.3892/ijmm.2019.4056

Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica

Authors:
- Chunsheng Yang
- Yang Yang
- Li Ma
- Guang‑Xian Zhang
- Fu‑Dong Shi
- Yaping Yan
- Guoqiang Chang
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Affiliations: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300052, P.R. China, Department of Neurosurgery and Neuro‑Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China, Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Published online on: January 9, 2019 https://doi.org/10.3892/ijmm.2019.4056
Pages: 1395-1405
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow‑derived mesenchymal stem cells (BM‑MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM‑MSCs from patients with NMO, which may influence any therapeutic effects. The present study aimed to compare the proliferation, differentiation and senescence of BM‑MSCs from patients with NMO with that of age‑ and sex‑matched healthy subjects. It was revealed that there were no significant differences in terms of cell morphology or differentiation capacities in the BM‑MSCs from the patients with NMO. However, in comparison with healthy controls, BM‑MSCs derived from the Patients with NMO exhibited a decreased proliferation rate, in addition to a decreased expression of several cell cycle‑promoting and proliferation‑associated genes. Furthermore, the cell death rate increased in BM‑MSCs from patients under normal culture conditions and an assessment of the gene expression profile further confirmed that the BM‑MSCs from patients with NMO were more vulnerable to senescence. Platelet‑derived growth factor (PDGF), as a major mitotic stimulatory factor for MSCs and a potent therapeutic cytokine in demyelinating disease, was able to overcome the decreased proliferation rate and increased senescence defects in BM‑MSCs from the patients with NMO. Taken together, the results from the present study have enabled the proposition of the possibility of combining the application of autologous BM‑MSCs and PDGF for refractory and severe patients with NMO in order to elicit improved therapeutic effects, or, at the least, to include PDGF as a necessary and standard growth factor in the current in vitro formula for the culture of NMO patient‑derived BM‑MSCs.

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1	Jarius S and Wildemann B: Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: A critical review of the literature. Brain Pathol. 23:661–683. 2013. View Article : Google Scholar : PubMed/NCBI
2	Vodopivec I, Matiello M and Prasad S: Treatment of neuromyelitis optica. Curr Opin Ophthalmol. 26:476–483. 2015. View Article : Google Scholar : PubMed/NCBI
3	Wingerchuk DM, Pittock SJ, Lucchinetti CF, Lennon VA and Weinshenker BG: A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 68:603–605. 2007. View Article : Google Scholar : PubMed/NCBI
4	Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, Takai Y, Takahashi T, Misu T, Elsone L, et al: Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 135:1834–1849. 2012. View Article : Google Scholar : PubMed/NCBI
5	Wingerchuk DM and Weinshenker BG: Neuromyelitis optica: Clinical predictors of a relapsing course and survival. Neurology. 60:848–853. 2003. View Article : Google Scholar : PubMed/NCBI
6	Cabre P, González-Quevedo A, Bonnan M, Saiz A, Olindo S, Graus F, Smadja D, Merle H, Thomas L and Cabrera-Gomez JA: Relapsing neuromyelitis optica: Long term history and clinical predictors of death. J Neurol Neurosurg Psychiatry. 80:1162–1164. 2009. View Article : Google Scholar : PubMed/NCBI
7	Watanabe S, Nakashima I, Misu T, Miyazawa I, Shiga Y, Fujihara K and Itoyama Y: Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult Scler. 13:128–132. 2007. View Article : Google Scholar : PubMed/NCBI
8	De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, Pascual CY, Aller MA, Arias J and Arnalich-Montiel F: Immunosuppressive properties of mesenchymal stem cells: Advances and applications. Curr Mol Med. 12:574–591. 2012. View Article : Google Scholar : PubMed/NCBI
9	Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC and Zhao W: Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab. 33:1322–1334. 2013. View Article : Google Scholar : PubMed/NCBI
10	Zhang X, Bowles AC, Semon JA, Scruggs BA, Zhang S, Strong AL, Gimble JM and Bunnell BA: Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model. PLoS One. 9:e850072014. View Article : Google Scholar : PubMed/NCBI
11	Li D, Chai J, Shen C, Han Y and Sun T: Human umbilical cord-derived mesenchymal stem cells differentiate into epidermal-like cells using a novel co-culture technique. Cytotechnology. 66:699–708. 2014. View Article : Google Scholar : PubMed/NCBI
12	Zacharek A, Shehadah A, Chen J, Cui X, Roberts C, Lu M and Chopp M: Comparison of bone marrow stromal cells derived from stroke and normal rats for stroke treatment. Stroke. 41:524–530. 2010. View Article : Google Scholar : PubMed/NCBI
13	Cohen JA: Mesenchymal stem cell transplantation in multiple sclerosis. J Neurol Sci. 333:43–49. 2013. View Article : Google Scholar : PubMed/NCBI
14	El-Akabawy G and Rashed LA: Beneficial effects of bone marrow-derived mesenchymal stem cell transplantation in a non-immune model of demyelination. Ann Anat. 198:11–20. 2015. View Article : Google Scholar : PubMed/NCBI
15	Fu Y, Yan Y, Qi Y, Yang L, Li T, Zhang N, Yu C, Su L, Zhang R, Shen Y, et al: Impact of autologous mesenchymal stem cell infusion on neuromyelitis optica spectrum disorder: A pilot, 2-year observation study. CNS Neurosci Ther. 22:677–685. 2016. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
17	Belotti D, Capelli C, Resovi A, Introna M and Taraboletti G: Thrombospondin-1 promotes mesenchymal stromal cell functions via TGFβ and in cooperation with PDGF. Matrix Biol. 55:106–116. 2016. View Article : Google Scholar : PubMed/NCBI
18	Papadopoulos N and Lennartsson J: The PDGF/PDGFR pathway as a drug target. Mol Aspects Med. 62:75–88. 2018. View Article : Google Scholar
19	Chen W, Baylink DJ, Brier-Jones J, Neises A, Kiroyan JB, Rundle CH, Lau KH and Zhang XB: PDGFB-based stem cell gene therapy increases bone strength in the mouse. Proc Natl Acad Sci USA. 112:E3893–E3900. 2015. View Article : Google Scholar : PubMed/NCBI
20	Solchaga LA, Bendele A, Shah V, Snel LB, Kestler HK, Dines JS and Hee CK: Comparison of the effect of intra-tendon applications of recombinant human platelet-derived growth factor-BB, platelet-rich plasma, steroids in a rat achilles tendon collagenase model. J Orthop Res. 32:145–150. 2014. View Article : Google Scholar
21	Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I and Weinshenker BG: A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet. 364:2106–2112. 2004. View Article : Google Scholar : PubMed/NCBI
22	Xiao J, Yang R, Biswas S, Qin X, Zhang M and Deng W: Mesenchymal stem cells and induced pluripotent stem cells as therapies for multiple sclerosis. Int J Mol Sci. 16:9283–9302. 2015. View Article : Google Scholar : PubMed/NCBI
23	Greco R, Bondanza A, Vago L, Moiola L, Rossi P, Furlan R, Martino G, Radaelli M, Martinelli V, Carbone MR, et al: Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica. Ann Neurol. 75:447–453. 2014. View Article : Google Scholar
24	Matiello M, Pittock SJ, Porrata L and Weinshenker BG: Failure of autologous hematopoietic stem cell transplantation to prevent relapse of neuromyelitis optica. Arch Neurol. 68:953–955. 2011. View Article : Google Scholar : PubMed/NCBI
25	Wilkins A, Kemp K, Ginty M, Hares K, Mallam E and Scolding N: Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem Cell Res. 3:63–70. 2009. View Article : Google Scholar : PubMed/NCBI
26	Cramer SC, Sur M, Dobkin BH, O'Brien C, Sanger TD, Trojanowski JQ, Rumsey JM, Hicks R, Cameron J, Chen D, et al: Harnessing neuroplasticity for clinical applications. Brain. 134:1591–1609. 2011. View Article : Google Scholar : PubMed/NCBI
27	Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH and Bang OY: STARTING collaborators: A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 28:1099–1106. 2010. View Article : Google Scholar : PubMed/NCBI
28	Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, et al: Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: An open-label phase 2a proof-of-concept study. Lancet Neurol. 11:150–156. 2012. View Article : Google Scholar : PubMed/NCBI
29	Park HJ, Shin JY, Lee BR, Kim HO and Lee PH: Mesenchymal stem cells augment neurogenesis in the subventricular zone and enhance differentiation of neural precursor cells into dopaminergic neurons in the substantia nigra of a parkinsonian model. Cell Transplant. 21:1629–1640. 2012. View Article : Google Scholar : PubMed/NCBI
30	Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Bernhard F, Verleysdonk S, Buadze M, Lourhmati A, Klopfer T, Schaumann F, Schmid B, et al: Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Res. 14:3–16. 2011. View Article : Google Scholar : PubMed/NCBI
31	Lu Z, Ye D, Qian L, Zhu L, Wang C, Guan D, Zhang X and Xu Y: Human umbilical cord mesenchymal stem cell therapy on neuromyelitis optica. Curr Neurovasc Res. 9:250–255. 2012. View Article : Google Scholar : PubMed/NCBI
32	Zaiss DMW, Gause WC, Osborne LC and Artis D: Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair. Immunity. 42:216–226. 2015. View Article : Google Scholar : PubMed/NCBI
33	Jeon H and Boo YC: Senescent endothelial cells are prone to TNF-α-induced cell death due to expression of FAS receptor. Biochem Biophys Res Commun. 438:277–282. 2013. View Article : Google Scholar : PubMed/NCBI
34	Ols ML, Cullen JL, Turqueti-Neves A, Giles J and Shlomchik MJ: Dendritic cells regulate extrafollicular autoreactive B cells via T cells expressing Fas and Fas ligand. Immunity. 45:1052–1065. 2016. View Article : Google Scholar : PubMed/NCBI
35	Cruz AC, Ramaswamy M, Ouyang C, Klebanoff CA, Sengupta P, Yamamoto TN, Meylan F, Thomas SK, Richoz N, Eil R, et al: Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction. Nat Commun. 7:138952016. View Article : Google Scholar : PubMed/NCBI
36	Ikezawa K, Hikita H, Shigekawa M, Iwahashi K, Eguchi H, Sakamori R, Tatsumi T and Takehara T: Increased Bcl-xL expression in pancreatic neoplasia promotes carcinogenesis by inhibiting senescence and apoptosis. Cell Mol Gastroenterol Hepatol. 4:185–200.e181. 2017. View Article : Google Scholar : PubMed/NCBI
37	Aouacheria A, Baghdiguian S, Lamb HM, Huska JD, Pineda FJ and Hardwick JM: Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins. Neurochem Int. 109:141–161. 2017. View Article : Google Scholar : PubMed/NCBI
38	Huang Y and Dreyfus CF: The role of growth factors as a therapeutic approach to demyelinating disease. Exp Neurol. 283:531–540. 2016. View Article : Google Scholar : PubMed/NCBI