Development of Mesenchymal Stem Cells Therapy for the Treatment of Polyglutamine SCA: From Bench to Bedside

Ho, Chih-Yuan; Lai, Hsiu-Yu; Wang, Ling-Mei; Soong, Bing-wen

doi:10.1007/978-3-031-24345-5_19

Chih-Yuan Ho⁶^na1,
Hsiu-Yu Lai⁶^na1,
Ling-Mei Wang⁶^na1 &
…
Bing-wen Soong^7,8^na1

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

362 Accesses

Abstract

This chapter focuses on the clinical application of mesenchymal stem cells (MSCs) for the treatment of spinocerebellar ataxia (SCA). SCA is a progressive neurodegenerative disease with complex etiologies. The therapy of SCA is an unmet medical need and the effective drug for this disease is yet to be developed. Fastly progressing gene- and cell-based therapies offer the alternative therapeutic approaches and may provide more potentials to treat the diseases resulting from multiple pathogenesis pathways. This chapter covers the overview of SCA, MSCs, and their potentials, functional assessment of MSCs on treating SCA in pre-clinical disease models, and potential mechanisms of actions (MoAs) exerted by MSCs. Moreover, clinical trials of utilizing adipose-derived MSCs (ADMSCs) for the treatment of spinocerebellar ataxia type 2 (SCA2) and spinocerebellar ataxia type 3 (SCA3) will be discussed in this chapter. Finally, the opportunities and challenges facing the development of MSCs as the therapeutics for SCA as well as other neurodegenerative diseases will also be discussed in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Chapter: USD 29.95; Price excludes VAT (USA)

eBook: USD 189.00; Price excludes VAT (USA)

Hardcover Book: USD 249.99; Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

¹⁸F-FDG:: ¹⁸F-fluorodeoxyglucose
AD:: Alzheimer’s disease
ADL:: Activities of daily living
ADMSCs:: adipose-derived MSCs
ALS:: amyotrophic lateral sclerosis
ATMP:: Advanced therapy medicinal products
ATP:: adenosine triphosphate
ATXN1:: ataxin-1 protein
ATXN2:: ataxin-2 protein
ATXN3 :: ataxin-3 gene
ATXN3:: ataxin-3 protein
ATXN7:: ataxin-7 protein
Aβ:: amyloid-β
BBB:: blood-brain barrier
BBS:: Berg Balance Scale
Bcl-2 :: B-cell lymphoma 2
BDNF:: brain-derived neurotrophic factor
BLA:: Biologics License Application
BMMSCs:: bone marrow-derived MSCs
CA :: cerebellar ataxia
CD:: cluster of differentiation
CM:: conditioned medium
CNS :: central nervous system
CO₂:: carbon dioxide
CSF :: cerebrospinal fluid
DNA:: deoxyribonucleic acid
EMA:: European Medicines Agency
ESCs:: embryonic stem cells
EVs :: exosomes
FDA:: Food and Drug Administration
FGF2:: fibroblast growth factor 2
GDNF:: glial cell line-derived neurotrophic factor
GFP:: green fluorescent protein
GPx:: glutathione peroxidase
HD:: Huntington’s disease
HLA-DR:: human leukocyte antigen-DR
ICAM-1:: intercellular adhesion molecule 1
ICARS:: International Cooperative Ataxia Rating Scale
IL-10:: interleukin-10
IL-1β:: interleukin-1 beta
iPSCs:: induced pluripotent stem cells
LPS :: lipopolysaccharide
miRNA:: microRNA
MoAs:: mechanisms of actions
MSA:: multiple system atrophy
MSA-C:: multiple system atrophy, cerebellar type
MSCs:: mesenchymal stem cells
mtDNA:: mitochondrial DNA
NT-3:: neurotrophin-3
ODAC:: Oncologic Drugs Advisory Committee
PD:: Parkinson’s disease
PET:: positron emission tomography
PGE2:: prostaglandin E2
PMDA:: Pharmaceuticals and Medical Devices Agency
polyQ:: polyglutamine
RMAT:: regenerative medicine advanced therapy
RNA:: ribonucleic acid
ROS:: reactive oxygen species
SARA:: Scale for the Assessment and Rating of Ataxia
SCA:: spinocerebellar ataxia
SCA1:: spinocerebellar ataxia type 1
SCA17:: spinocerebellar ataxia type 17
SCA2:: spinocerebellar ataxia type 2
SCA3:: spinocerebellar ataxia type 3
SCA6:: spinocerebellar ataxia type 6
SCA7:: spinocerebellar ataxia type 7
SOT:: Sensory Organization Testing
SR-aGVHD:: steroid-refractory acute graft versus host disease
TNFα:: tumor necrosis factor alpha
TSG6:: TNFα-stimulated gene-6
UCBMSCs:: umbilical cord blood-derived MSCs
UCMSCs:: umbilical cord-derived MSCs
VCAM-1:: vascular cell adhesion molecule
VEGF:: vascular endothelial growth factor

References

Akhtar A, Andleeb A, Waris TS, Bazzar M, Moradi A-R, Awan NR, Yar M. Neurodegenerative diseases and effective drug delivery: a review of challenges and novel therapeutics. J Control Release. 2021;330:1152–67. https://doi.org/10.1016/j.jconrel.2020.11.021.
Article CAS PubMed Google Scholar
Amin A, Perera ND, Beart PM, Turner BJ, Shabanpoor F. Amyotrophic lateral sclerosis and autophagy: dysfunction and therapeutic targeting. Cells (Basel, Switzerland). 2020;9(11):2413. https://doi.org/10.3390/cells9112413.
Article CAS Google Scholar
Andrzejewska A, Lukomska B, Janowski M. Concise review: mesenchymal stem cells: from roots to boost. Stem Cells (Dayton, Ohio). 2019;37(7):855–64. https://doi.org/10.1002/stem.3016.
Article PubMed Google Scholar
Angeloni C, Gatti M, Prata C, Hrelia S, Maraldi T. Role of mesenchymal stem cells in counteracting oxidative stress-related neurodegeneration. Int J Mol Sci. 2020;21(9):3299. https://doi.org/10.3390/ijms21093299.
Article CAS PubMed PubMed Central Google Scholar
Appelt PA, Comella K, de Souza LAPS, Luvizutto GJ. Effect of stem cell treatment on functional recovery of spinocerebellar ataxia: systematic review and meta-analysis. Cerebell Atax. 2021;8(1):8. https://doi.org/10.1186/s40673-021-00130-8.
Article Google Scholar
Araujo J, Breuer P, Dieringer S, Krauss S, Dorn S, Zimmermann K, et al. FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3. Hum Mol Genet. 2011;20(15):2928–41. https://doi.org/10.1093/hmg/ddr197.
Article CAS PubMed Google Scholar
Ashizawa T, Figueroa KP, Perlman SL, Gomez CM, Wilmot GR, Schmahmann JD, et al. Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J Rare Dis. 2013;8(1):177. https://doi.org/10.1186/1750-1172-8-177.
Article PubMed PubMed Central Google Scholar
Ashizawa T, Öz G, Paulson HL. Spinocerebellar ataxias: prospects and challenges for therapy development. Nat Rev Neurol. 2018;14(10):590–605. https://doi.org/10.1038/s41582-018-0051-6.
Article PubMed PubMed Central Google Scholar
Atta RM, Ameen AM, Korayem HE, Abogresha N, El-Wazir Y. Adipose tissue-derived mesenchymal stem cells have better restorative capacity than bone marrow-derived cells in a cerebellar ataxia rat model. Arch Med Sci. 2020; https://doi.org/10.5114/aoms.2020.100833.
Baez-Jurado E, Guio-Vega G, Hidalgo-Lanussa O, González J, Echeverria V, Ashraf GM, et al. Mitochondrial neuroglobin is necessary for protection induced by conditioned medium from human adipose-derived mesenchymal stem cells in astrocytic cells subjected to scratch and metabolic injury. Mol Neurobiol. 2019;56(7):5167–87. https://doi.org/10.1007/s12035-018-1442-9.
Article CAS PubMed Google Scholar
Bao X, Wei J, Feng M, Lu S, Li G, Dou W, et al. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Brain Res. 2011;1367:103–13. https://doi.org/10.1016/j.brainres.2010.10.063.
Article CAS PubMed Google Scholar
Besson MT, Alegría K, Garrido-Gerter P, Barros LF, Liévens J-C. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model. PLoS One. 2015;10(3):e0118765. https://doi.org/10.1371/journal.pone.0118765.
Article CAS PubMed PubMed Central Google Scholar
Bodart-Santos V, de Carvalho LRP, de Godoy MA, Batista AF, Saraiva LM, Lima LG, et al. Extracellular vesicles derived from human Wharton’s jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers. Stem Cell Res Ther. 2019;10(1):332. https://doi.org/10.1186/s13287-019-1432-5.
Article CAS PubMed PubMed Central Google Scholar
Bonafede R, Scambi I, Peroni D, Potrich V, Boschi F, Benati D, et al. Exosome derived from murine adipose-derived stromal cells: neuroprotective effect on in vitro model of amyotrophic lateral sclerosis. Exp Cell Res. 2016;340(1):150–8. https://doi.org/10.1016/j.yexcr.2015.12.009.
Article CAS PubMed Google Scholar
Brooker SM, Edamakanti CR, Akasha SM, Kuo S-H, Opal P. Spinocerebellar ataxia clinical trials: opportunities and challenges. Ann Clin Transl Neurol. 2021;8(7):1543–56. https://doi.org/10.1002/acn3.51370.
Article PubMed PubMed Central Google Scholar
Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease. Science (New York, NY). 2017;357(6357):1255–61. https://doi.org/10.1126/science.aam9080.
Article CAS Google Scholar
Byun J, Kang E, Park S, Kang D. Isolation of human mesenchymal stem cells from the skin and their neurogenic differentiation in vitro. J Korean Assoc Oral Maxillofac Surg. 2012;38:343–53.
Article Google Scholar
Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, et al. Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases. J Clin Invest. 2019;129(10):4539–49. https://doi.org/10.1172/JCI129987.
Article PubMed PubMed Central Google Scholar
Calió ML, Marinho DS, Ko GM, Ribeiro RR, Carbonel AF, Oyama LM, et al. Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model. Free Radic Biol Med. 2014;70:141–54. https://doi.org/10.1016/j.freeradbiomed.2014.01.024.
Article CAS PubMed Google Scholar
Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9(5):641–50. https://doi.org/10.1002/jor.1100090504.
Article CAS PubMed Google Scholar
Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–5. https://doi.org/10.1016/j.stem.2011.06.008.
Article CAS PubMed PubMed Central Google Scholar
Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–84. https://doi.org/10.1002/jcb.20886.
Article CAS PubMed Google Scholar
Ceccariglia S, Cargnoni A, Silini AR, Parolini O. Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells. Autophagy. 2020;16(1):28–37. https://doi.org/10.1080/15548627.2019.1630223.
Article CAS PubMed Google Scholar
Cenini G, Lloret A, Cascella R. Oxidative stress in neurodegenerative diseases: from a mitochondrial point of view. Oxidative Med Cell Longev. 2019;2019:2105607. https://doi.org/10.1155/2019/2105607.
Article CAS Google Scholar
Chang Y-K, Chen M-H, Chiang Y-H, Chen Y-F, Ma W-H, Tseng C-Y, et al. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells. J Biomed Sci. 2011;18(1):54. https://doi.org/10.1186/1423-0127-18-54.
Article CAS PubMed PubMed Central Google Scholar
Chang K-H, Chen W-L, Lee L-C, Lin C-H, Kung P-J, Lin T-H, et al. Aqueous extract of Paeonia lactiflora and paeoniflorin as aggregation reducers targeting chaperones in cell models of spinocerebellar ataxia 3. Evid Based Complement Alternat Med. 2013;2013:471659. https://doi.org/10.1155/2013/471659.
Article PubMed PubMed Central Google Scholar
Chen Y-S, Hong Z-X, Lin S-Z, Harn H-J. Identifying therapeutic targets for spinocerebellar ataxia type 3/Machado-Joseph disease through integration of pathological biomarkers and therapeutic strategies. Int J Mol Sci. 2020;21(9):3063. https://doi.org/10.3390/ijms21093063.
Article CAS PubMed PubMed Central Google Scholar
Cornelius N, Wardman JH, Hargreaves IP, Neergheen V, Bie AS, Tümer Z, et al. Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: effect of coenzyme Q10 supplementation on these parameters. Mitochondrion. 2017;34:103–14. https://doi.org/10.1016/j.mito.2017.03.001.
Article CAS PubMed Google Scholar
Cremades N, Cohen SIA, Deas E, Abramov AY, Chen AY, Orte A, et al. Direct observation of the interconversion of normal and toxic forms of α-synuclein. Cell. 2012;149(5):1048–59. https://doi.org/10.1016/j.cell.2012.03.037.
Article CAS PubMed PubMed Central Google Scholar
Croce KR, Yamamoto A. A role for autophagy in Huntington’s disease. Neurobiol Dis. 2019;122:16–22. https://doi.org/10.1016/j.nbd.2018.08.010.
Article CAS PubMed Google Scholar
Cvetanovic M, Ingram M, Orr H, Opal P. Early activation of microglia and astrocytes in mouse models of spinocerebellar ataxia type 1. Neuroscience. 2015;289:289–99. https://doi.org/10.1016/j.neuroscience.2015.01.003.
Article CAS PubMed Google Scholar
da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119(Pt 11):2204–13. https://doi.org/10.1242/jcs.02932.
Article CAS PubMed Google Scholar
de Assis AM, Saute JAM, Longoni A, Haas CB, Torrez VR, Brochier AW, et al. Peripheral oxidative stress biomarkers in spinocerebellar ataxia type 3/Machado-Joseph disease. Front Neurol. 2017;8:485. https://doi.org/10.3389/fneur.2017.00485.
Article PubMed PubMed Central Google Scholar
De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44(8):1928–42. https://doi.org/10.1002/1529-0131(200108)44:8<1928::AID-ART331>3.0.CO;2-P.
Article PubMed Google Scholar
de Oliveira MR, Custódio de Souza IC, Fürstenau CR. Promotion of mitochondrial protection by naringenin in methylglyoxal-treated SH-SY5Y cells: involvement of the Nrf2/GSH axis. Chem Biol Interact. 2019;310(108728):108728. https://doi.org/10.1016/j.cbi.2019.108728.
Article CAS PubMed Google Scholar
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7(1):11–20. https://doi.org/10.1016/j.cmet.2007.10.002.
Article CAS PubMed Google Scholar
Dennis A-G, Almaguer-Mederos LE, Raúl R-A, Roberto R-L, Luis V-P, Dany C-A, et al. Redox imbalance associates with clinical worsening in spinocerebellar ataxia type 2. Oxidative Med Cell Longev. 2021;2021:9875639. https://doi.org/10.1155/2021/9875639.
Article CAS Google Scholar
Di Meo S, Reed TT, Venditti P, Victor VM. Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Med Cell Longev. 2016;2016:1245049. https://doi.org/10.1155/2016/1245049.
Article CAS Google Scholar
Diallo A, Jacobi H, Tezenas du Montcel S, Klockgether T. Natural history of most common spinocerebellar ataxia: a systematic review and meta-analysis. J Neurol. 2021;268(8):2749–56. https://doi.org/10.1007/s00415-020-09815-2.
Article PubMed Google Scholar
Díaz-García CM, Mongeon R, Lahmann C, Koveal D, Zucker H, Yellen G. Neuronal stimulation triggers neuronal glycolysis and not lactate uptake. Cell Metab. 2017;26(2):361–374.e4. https://doi.org/10.1016/j.cmet.2017.06.021.
Article CAS PubMed PubMed Central Google Scholar
Doi D, Magotani H, Kikuchi T, Ikeda M, Hiramatsu S, Yoshida K, et al. Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease. Nat Commun. 2020;11(1):3369. https://doi.org/10.1038/s41467-020-17165-w.
Article CAS PubMed PubMed Central Google Scholar
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7. https://doi.org/10.1080/14653240600855905.
Article CAS PubMed Google Scholar
Dongmei H, Jing L, Mei X, Ling Z, Hongmin Y, Zhidong W, et al. Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells. Cytotherapy. 2011;13(8):913–7. https://doi.org/10.3109/14653249.2011.579958.
Article PubMed Google Scholar
Duarte-Silva S, Neves-Carvalho A, Soares-Cunha C, Silva JM, Teixeira-Castro A, Vieira R, et al. Neuroprotective effects of creatine in the CMVMJD135 mouse model of spinocerebellar ataxia type 3. Move Disord. 2018;33(5):815–26. https://doi.org/10.1002/mds.27292.
Article CAS Google Scholar
Elfawy HA, Das B. Crosstalk between mitochondrial dysfunction, oxidative stress, and age-related neurodegenerative disease: etiologies and therapeutic strategies. Life Sci. 2019;218:165–84. https://doi.org/10.1016/j.lfs.2018.12.029.
Article CAS PubMed Google Scholar
Folger A, Wang Y. The cytotoxicity and clearance of mutant Huntingtin and other misfolded proteins. Cells (Basel, Switzerland). 2021;10(11) https://doi.org/10.3390/cells10112835.
Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6(2):230–47. Opgehaal van https://www.ncbi.nlm.nih.gov/pubmed/5654088
Article CAS PubMed Google Scholar
Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of Guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3(4):393–403. https://doi.org/10.1111/j.1365-2184.1970.tb00347.x.
Article CAS PubMed Google Scholar
Garcia-Contreras M, Thakor AS. Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia. Cell Death Discov. 2021;7(1):98. https://doi.org/10.1038/s41420-021-00471-7.
Article CAS PubMed PubMed Central Google Scholar
Ghannam S, Pène J, Moquet-Torcy G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol. 2010;185(1):302–12. https://doi.org/10.4049/jimmunol.0902007.
Article CAS PubMed Google Scholar
Gkekas I, Gioran A, Boziki MK, Grigoriadis N, Chondrogianni N, Petrakis S. Oxidative stress and neurodegeneration: interconnected processes in PolyQ diseases. Antioxidants (Basel, Switzerland). 2021;10(9):1450. https://doi.org/10.3390/antiox10091450.
Article CAS PubMed Google Scholar
Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3–12. https://doi.org/10.1002/path.2697.
Article CAS PubMed PubMed Central Google Scholar
Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11(4):367–8. https://doi.org/10.1038/nm0405-367.
Article CAS PubMed Google Scholar
Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20(6):661–9. https://doi.org/10.1096/fj.05-5211com.
Article CAS PubMed Google Scholar
Gomzikova MO, James V, Rizvanov AA. Mitochondria donation by mesenchymal stem cells: current understanding and mitochondria transplantation strategies. Front Cell Dev Biol. 2021;9:653322. https://doi.org/10.3389/fcell.2021.653322.
Article PubMed PubMed Central Google Scholar
Gu Y, Zhang Y, Bi Y, Liu J, Tan B, Gong M, et al. Mesenchymal stem cells suppress neuronal apoptosis and decrease IL-10 release via the TLR2/NFκB pathway in rats with hypoxic-ischemic brain damage. Mol Brain. 2015;8(1):65. https://doi.org/10.1186/s13041-015-0157-3.
Article CAS PubMed PubMed Central Google Scholar
Guillamat-Prats R. The role of MSC in wound healing, scarring and regeneration. Cells (Basel, Switzerland). 2021;10(7):1729. https://doi.org/10.3390/cells10071729.
Article CAS Google Scholar
Guo Y, Yu Y, Hu S, Chen Y, Shen Z. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis. 2020;11(5):349. https://doi.org/10.1038/s41419-020-2542-9.
Article PubMed PubMed Central Google Scholar
Harmuth T, Prell-Schicker C, Weber JJ, Gellerich F, Funke C, Drießen S, et al. Mitochondrial morphology, function and homeostasis are impaired by expression of an N-terminal calpain cleavage fragment of ataxin-3. Front Mol Neurosci. 2018;11:368. https://doi.org/10.3389/fnmol.2018.00368.
Article CAS PubMed PubMed Central Google Scholar
Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9(1):12. https://doi.org/10.1186/1478-811X-9-12.
Article CAS PubMed PubMed Central Google Scholar
Healy ME, Bergin R, Mahon BP, English K. Mesenchymal stromal cells protect against caspase 3-mediated apoptosis of CD19(+) peripheral B cells through contact-dependent upregulation of VEGF. Stem Cells Dev. 2015;24(20):2391–402. https://doi.org/10.1089/scd.2015.0089.
Article CAS PubMed Google Scholar
Hentze H, Soong PL, Wang ST, Phillips BW, Putti TC, Dunn NR. Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res. 2009;2(3):198–210. https://doi.org/10.1016/j.scr.2009.02.002.
Article PubMed Google Scholar
Hernández AE, García E. Mesenchymal stem cell therapy for Alzheimer’s disease. Stem Cells Int. 2021;2021:7834421. https://doi.org/10.1155/2021/7834421.
Article CAS PubMed PubMed Central Google Scholar
Herrera MB, Bruno S, Buttiglieri S, Tetta C, Gatti S, Deregibus MC, et al. Isolation and characterization of a stem cell population from adult human liver. Stem Cells (Dayton, Ohio). 2006;24(12):2840–50. https://doi.org/10.1634/stemcells.2006-0114.
Article CAS PubMed Google Scholar
Hoban DB, Howard L, Dowd E. GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease. Neuroscience. 2015;303:402–11. https://doi.org/10.1016/j.neuroscience.2015.07.014.
Article CAS PubMed Google Scholar
Hong CT, Chau K-Y, Schapira AHV. Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models. Sci Rep. 2016;6:25344. https://doi.org/10.1038/srep25344.
Article CAS PubMed PubMed Central Google Scholar
Hsu J-Y, Jhang Y-L, Cheng P-H, Chang Y-F, Mao S-H, Yang H-I, et al. The truncated C-terminal fragment of mutant ATXN3 disrupts mitochondria dynamics in spinocerebellar ataxia type 3 models. Front Mol Neurosci. 2017;10:196. https://doi.org/10.3389/fnmol.2017.00196.
Article CAS PubMed PubMed Central Google Scholar
Huda F, Fan Y, Suzuki M, Konno A, Matsuzaki Y, Takahashi N, Chan JKY, Hirai H. Fusion of human fetal mesenchymal stem cells with “degenerating” cerebellar neurons in spinocerebellar ataxia type 1 model mice. PLoS One. 2016;11(11):e0164202. https://doi.org/10.1371/journal.pone.0164202.
Article CAS PubMed PubMed Central Google Scholar
In’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GMJS, Claas FHJ, Fibbe WE, Kanhai HHH. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells (Dayton, Ohio). 2004;22(7):1338–45. https://doi.org/10.1634/stemcells.2004-0058.
Article PubMed Google Scholar
Ionescu L, Byrne RN, van Haaften T, Vadivel A, Alphonse RS, Rey-Parra GJ, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. 2012;303(11):L967–77. https://doi.org/10.1152/ajplung.00144.2011.
Article CAS PubMed PubMed Central Google Scholar
Ising C, Heneka MT. Functional and structural damage of neurons by innate immune mechanisms during neurodegeneration. Cell Death Dis. 2018;9(2):120. https://doi.org/10.1038/s41419-017-0153-x.
Article CAS PubMed PubMed Central Google Scholar
Jacobi H, du Montcel ST, Bauer P, Giunti P, Cook A, Labrum R, et al. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study. Lancet Neurol. 2015;14(11):1101–8. https://doi.org/10.1016/S1474-4422(15)00202-1.
Article PubMed Google Scholar
Jezierska-Wozniak K, Sinderewicz E, Czelejewska W, Wojtacha P, Barczewska M, Maksymowicz W. Influence of bone marrow-derived mesenchymal stem cell therapy on oxidative stress intensity in minimally conscious state patients. J Clin Med. 2020;9(3):683. https://doi.org/10.3390/jcm9030683.
Article PubMed PubMed Central Google Scholar
Jin J-L, Liu Z, Lu Z-J, Guan D-N, Wang C, Chen Z-B, et al. Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res. 2013;10(1):11–20. https://doi.org/10.2174/156720213804805936.
Article CAS PubMed Google Scholar
Jones J, Jaramillo-Merchán J, Bueno C, Pastor D, Viso-León M, Martínez S. Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia. Neurobiol Dis. 2010;40(2):415–23. https://doi.org/10.1016/j.nbd.2010.07.001.
Article PubMed Google Scholar
Jones J, Estirado A, Redondo C, Bueno C, Martínez S. Human adipose stem cell-conditioned medium increases survival of Friedreich’s ataxia cells submitted to oxidative stress. Stem Cells Dev. 2012;21(15):2817–26. https://doi.org/10.1089/scd.2012.0029.
Article CAS PubMed Google Scholar
Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med. 2010;5(6):933–46. https://doi.org/10.2217/rme.10.72.
Article PubMed Google Scholar
Jung KJ, Lee GW, Park CH, Lee TJ, Kim JY, Sung EG, et al. Mesenchymal stem cells decrease oxidative stress in the bowels of interleukin-10 knockout mice. Gut Liver. 2020;14(1):100–7. https://doi.org/10.5009/gnl18438.
Article CAS PubMed Google Scholar
Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells (Dayton, Ohio). 2006;24(5):1294–301. https://doi.org/10.1634/stemcells.2005-0342.
Article CAS PubMed Google Scholar
Khan S, Khan RS, Newsome PN. Cell therapy for liver disease: from promise to reality. Semin Liver Dis. 2020;40(4):411–26. https://doi.org/10.1055/s-0040-1717096.
Article PubMed Google Scholar
Kim HJ, Cho KR, Jang H, Lee NK, Jung YH, Kim JP, et al. Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial. Alzheimers Res Ther. 2021;13(1):154. https://doi.org/10.1186/s13195-021-00897-2.
Article CAS PubMed PubMed Central Google Scholar
Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004;94(5):678–85. https://doi.org/10.1161/01.RES.0000118601.37875.AC.
Article CAS PubMed Google Scholar
Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, et al. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci. 2005;12(1):47–57. https://doi.org/10.1007/s11373-004-8183-7.
Article CAS PubMed Google Scholar
Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101(9):3722–9. https://doi.org/10.1182/blood-2002-07-2104.
Article CAS PubMed Google Scholar
Kristensen LV, Oppermann FS, Rauen MJ, Fog K, Schmidt T, Schmidt J, et al. Mass spectrometry analyses of normal and polyglutamine expanded ataxin-3 reveal novel interaction partners involved in mitochondrial function. Neurochem Int. 2018;112:5–17. https://doi.org/10.1016/j.neuint.2017.10.013.
Article CAS PubMed Google Scholar
Laço MN, Oliveira CR, Paulson HL, Rego AC. Compromised mitochondrial complex II in models of Machado-Joseph disease. Biochim Biophys Acta. 2012;1822(2):139–49. https://doi.org/10.1016/j.bbadis.2011.10.010.
Article CAS PubMed Google Scholar
Laidou S, Alanis-Lobato G, Pribyl J, Raskó T, Tichy B, Mikulasek K, et al. Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery. Redox Biol. 2020;32(101458):101458. https://doi.org/10.1016/j.redox.2020.101458.
Article CAS PubMed PubMed Central Google Scholar
Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringdén O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003;57(1):11–20. https://doi.org/10.1046/j.1365-3083.2003.01176.x.
Article PubMed Google Scholar
Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, Oh W, et al. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer’s disease mouse model through modulation of neuroinflammation. Neurobiol Aging. 2012;33(3):588–602. https://doi.org/10.1016/j.neurobiolaging.2010.03.024.
Article CAS PubMed Google Scholar
Lévy E, El Banna N, Baïlle D, Heneman-Masurel A, Truchet S, Rezaei H, et al. Causative links between protein aggregation and oxidative stress: a review. Int J Mol Sci. 2019;20(16):3896. https://doi.org/10.3390/ijms20163896.
Article CAS PubMed PubMed Central Google Scholar
Li X, Liu H, Fischhaber PL, Tang T-S. Toward therapeutic targets for SCA3: insight into the role of Machado-Joseph disease protein ataxin-3 in misfolded proteins clearance. Prog Neurobiol. 2015;132:34–58. https://doi.org/10.1016/j.pneurobio.2015.06.004.
Article CAS PubMed Google Scholar
Liang X, Ding Y, Zhang Y, Tse H-F, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014;23(9):1045–59. https://doi.org/10.3727/096368913X667709.
Article PubMed Google Scholar
Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787–95. https://doi.org/10.1038/nature05292.
Article CAS PubMed Google Scholar
Lin C-H, Wu Y-R, Yang J-M, Chen W-L, Chao C-Y, Chen I-C, et al. Novel lactulose and melibiose targeting autophagy to reduce PolyQ aggregation in cell models of spinocerebellar ataxia 3. CNS Neurol Disord Drug Targets. 2016;15(3):351–9. https://doi.org/10.2174/1871527314666150821101522.
Article CAS PubMed Google Scholar
Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One. 2014;9(9):e107001. https://doi.org/10.1371/journal.pone.0107001.
Article CAS PubMed PubMed Central Google Scholar
Liu X-L, Zhang W, Tang S-J. Intracranial transplantation of human adipose-derived stem cells promotes the expression of neurotrophic factors and nerve repair in rats of cerebral ischemia-reperfusion injury. Int J Clin Exp Pathol. 2014;7(1):174–83. Opgehaal van https://www.ncbi.nlm.nih.gov/pubmed/24427337
PubMed Google Scholar
Lo Sicco C, Reverberi D, Balbi C, Ulivi V, Principi E, Pascucci L, et al. Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects: endorsement of macrophage polarization. Stem Cells Transl Med. 2017;6(3):1018–28. https://doi.org/10.1002/sctm.16-0363.
Article CAS PubMed PubMed Central Google Scholar
Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011;27(1):441–64. https://doi.org/10.1146/annurev-cellbio-092910-154237.
Article CAS PubMed Google Scholar
Ma T, Gong K, Ao Q, Yan Y, Song B, Huang H, et al. Intracerebral transplantation of adipose-derived mesenchymal stem cells alternatively activates microglia and ameliorates neuropathological deficits in Alzheimer’s disease mice. Cell Transplant. 2013;22(1_suppl):S113–26. https://doi.org/10.3727/096368913X672181.
Article Google Scholar
Malagelada C, Jin ZH, Jackson-Lewis V, Przedborski S, Greene LA. Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson’s disease. J Neurosci Off J Soc Neurosci. 2010;30(3):1166–75. https://doi.org/10.1523/JNEUROSCI.3944-09.2010.
Article CAS Google Scholar
Marfia G, Navone SE, Hadi LA, Paroni M, Berno V, Beretta M, et al. The adipose mesenchymal stem cell secretome inhibits inflammatory responses of microglia: evidence for an involvement of sphingosine-1-phosphate signalling. Stem Cells Dev. 2016;25(14):1095–107. https://doi.org/10.1089/scd.2015.0268.
Article CAS PubMed Google Scholar
Markov A, Thangavelu L, Aravindhan S, Zekiy AO, Jarahian M, Chartrand MS, et al. Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders. Stem Cell Res Ther. 2021;12(1):192. https://doi.org/10.1186/s13287-021-02265-1.
Article CAS PubMed PubMed Central Google Scholar
McElreavey KD, Irvine AI, Ennis KT, McLean WH. Isolation, culture and randomization of fibroblast-like cells derived from the Wharton’s jelly portion of human umbilical cord. Biochem Soc Trans. 1991;19(1):29S. https://doi.org/10.1042/bst019029s.
Article CAS PubMed Google Scholar
McIntosh CS, Li D, Wilton SD, Aung-Htut MT. Polyglutamine ataxias: our current molecular understanding and what the future holds for antisense therapies. Biomedicine. 2021;9(11):1499. https://doi.org/10.3390/biomedicines9111499.
Article CAS Google Scholar
McLoughlin HS, Moore LR, Chopra R, Komlo R, McKenzie M, Blumenstein KG, et al. Oligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice. Ann Neurol. 2018;84(1):64–77. https://doi.org/10.1002/ana.25264.
Article CAS PubMed PubMed Central Google Scholar
Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain J Neurol. 2010;133(Pt 1):93–104. https://doi.org/10.1093/brain/awp292.
Article CAS Google Scholar
Minakawa EN, Nagai Y. Protein aggregation inhibitors as disease-modifying therapies for polyglutamine diseases. Front Neurosci. 2021;15:621996. https://doi.org/10.3389/fnins.2021.621996.
Article PubMed PubMed Central Google Scholar
Mohamed-Ahmed S, Fristad I, Lie SA, Suliman S, Mustafa K, Vindenes H, Idris SB. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison. Stem Cell Res Ther. 2018;9(1):168. https://doi.org/10.1186/s13287-018-0914-1.
Article CAS PubMed PubMed Central Google Scholar
Muddapu VR, Dharshini SAP, Chakravarthy VS, Gromiha MM. Neurodegenerative diseases — is metabolic deficiency the root cause? Front Neurosci. 2020;14:213. https://doi.org/10.3389/fnins.2020.00213.
Article PubMed PubMed Central Google Scholar
Mukai T, Sei K, Nagamura-Inoue T. Mesenchymal stromal cells perspective: new potential therapeutic for the treatment of neurological diseases. Pharmaceutics. 2021;13(8):1159. https://doi.org/10.3390/pharmaceutics13081159.
Article CAS PubMed PubMed Central Google Scholar
Nam Y, Yoon D, Hong J, Kim MS, Lee TY, Kim KS, et al. Therapeutic effects of human mesenchymal stem cells in a mouse model of cerebellar ataxia with neuroinflammation. J Clin Med. 2020;9(11):3654. https://doi.org/10.3390/jcm9113654.
Article CAS PubMed PubMed Central Google Scholar
Nascimento-Ferreira I, Nóbrega C, Vasconcelos-Ferreira A, Onofre I, Albuquerque D, Aveleira C, et al. Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado-Joseph disease. Brain J Neurol. 2013;136(Pt 7):2173–88. https://doi.org/10.1093/brain/awt144.
Article Google Scholar
Nishizawa M, Onodera O, Hirakawa A, Shimizu Y, Yamada M, Rovatirelin Study Group. Effect of rovatirelin in patients with cerebellar ataxia: two andomized double-blind placebo-controlled phase 3 trials. J Neurol Neurosurg Psychiatry. 2020;91(3):254–62. https://doi.org/10.1136/jnnp-2019-322168.
Article PubMed Google Scholar
Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013;19(8):983–97. https://doi.org/10.1038/nm.3232.
Article CAS PubMed Google Scholar
Ocampo A, Zambrano A, Barrientos A. Suppression of polyglutamine-induced cytotoxicity in Saccharomyces cerevisiae by enhancement of mitochondrial biogenesis. FASEB J. 2010;24(5):1431–41. https://doi.org/10.1096/fj.09-148601.
Article CAS PubMed Google Scholar
Oliveira Miranda C. Mesenchymal stem cells for lysosomal storage and polyglutamine disorders: possible shared mechanisms. Eur J Clin Investig. 2021;e13707 https://doi.org/10.1111/eci.13707.
Oliveira Miranda C, Marcelo A, Silva TP, Barata J, Vasconcelos-Ferreira A, Pereira D, et al. Repeated mesenchymal stromal cell treatment sustainably alleviates Machado-Joseph disease. Mol Ther J Am Soc Gene Ther. 2018;26(9):2131–51. https://doi.org/10.1016/j.ymthe.2018.07.007.
Article CAS Google Scholar
Onofre I, Mendonça N, Lopes S, Nobre R, de Melo JB, Carreira IM, et al. Fibroblasts of Machado Joseph disease patients reveal autophagy impairment. Sci Rep. 2016;6:28220. https://doi.org/10.1038/srep28220.
Article CAS PubMed PubMed Central Google Scholar
Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Belló C, et al. Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res Genet Toxicol Environ Mutagen. 2013;757(2):99–103. https://doi.org/10.1016/j.mrgentox.2013.06.023.
Article CAS PubMed Google Scholar
Park H, Chang K-A. Therapeutic potential of repeated intravenous transplantation of human adipose-derived stem cells in subchronic MPTP-induced Parkinson’s disease mouse model. Int J Mol Sci. 2020;21(21):8129. https://doi.org/10.3390/ijms21218129.
Article CAS PubMed PubMed Central Google Scholar
Park HJ, Shin JY, Kim HN, Oh SH, Lee PH. Neuroprotective effects of mesenchymal stem cells through autophagy modulation in a parkinsonian model. Neurobiol Aging. 2014;35(8):1920–8. https://doi.org/10.1016/j.neurobiolaging.2014.01.028.
Article CAS PubMed Google Scholar
Park K-R, Hwang CJ, Yun H-M, Yeo IJ, Choi D-Y, Park P-H, et al. Prevention of multiple system atrophy using human bone marrow-derived mesenchymal stem cells by reducing polyamine and cholesterol-induced neural damages. Stem Cell Res Ther. 2020;11(1):63. https://doi.org/10.1186/s13287-020-01590-1.
Article CAS PubMed PubMed Central Google Scholar
Paulson HL, Shakkottai VG, Clark HB, Orr HT. Polyglutamine spinocerebellar ataxias — from genes to potential treatments. Nat Rev Neurosci. 2017;18(10):613–26. https://doi.org/10.1038/nrn.2017.92.
Article CAS PubMed PubMed Central Google Scholar
Phinney DG. Functional heterogeneity of mesenchymal stem cells: implications for cell therapy. J Cell Biochem. 2012;113(9):2806–12. https://doi.org/10.1002/jcb.24166.
Article CAS PubMed Google Scholar
Pohl F, Teixeira-Castro A, Costa MD, Lindsay V, Fiúza-Fernandes J, Goua M, et al. GST-4-dependent suppression of neurodegeneration in C. elegans models of Parkinson’s and Machado-Joseph disease by rapeseed pomace extract supplementation. Front Neurosci. 2019;13:1091. https://doi.org/10.3389/fnins.2019.01091.
Article PubMed PubMed Central Google Scholar
Pollock K, Dahlenburg H, Nelson H, Fink KD, Cary W, Hendrix K, et al. Human mesenchymal stem cells genetically engineered to overexpress brain-derived neurotrophic factor improve outcomes in Huntington’s disease mouse models. Mol Ther J Am Soc Gene Ther. 2016;24(5):965–77. https://doi.org/10.1038/mt.2016.12.
Article CAS Google Scholar
Puig-Pijuan T, de Godoy MA, Pinheiro Carvalho LR, Bodart-Santos V, Lindoso RS, Pimentel-Coelho PM, Mendez-Otero R. Human Wharton’s jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms. Future Sci OA. 2020;6(9):FSO627. https://doi.org/10.2144/fsoa-2020-0036.
Article CAS PubMed PubMed Central Google Scholar
Radi E, Formichi P, Battisti C, Federico A. Apoptosis and oxidative stress in neurodegenerative diseases. J Alzheimer’s Dis. 2014;42 Suppl 3(s3):S125–52. https://doi.org/10.3233/JAD-132738.
Article CAS Google Scholar
Raposo M, Ramos A, Santos C, Kazachkova N, Teixeira B, Bettencourt C, Lima M. Accumulation of mitochondrial DNA common deletion since the preataxic stage of Machado-Joseph disease. Mol Neurobiol. 2019;56(1):119–24. https://doi.org/10.1007/s12035-018-1069-x.
Article CAS PubMed Google Scholar
Reina CP, Zhong X, Pittman RN. Proteotoxic stress increases nuclear localization of ataxin-3. Hum Mol Genet. 2010;19(2):235–49. https://doi.org/10.1093/hmg/ddp482.
Article CAS PubMed Google Scholar
Ren G, Zhao X, Zhang L, Zhang J, L’Huillier A, Ling W, et al. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol. 2010;184(5):2321–8. https://doi.org/10.4049/jimmunol.0902023.
Article CAS PubMed Google Scholar
Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells (Dayton, Ohio). 2003;21(1):105–10. https://doi.org/10.1634/stemcells.21-1-105.
Article PubMed Google Scholar
Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42(3):174–83. https://doi.org/10.1159/000358801.
Article PubMed Google Scholar
Ruetenik AL, Ocampo A, Ruan K, Zhu Y, Li C, Zhai RG, Barrientos A. Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging. Microbial Cell (Graz, Austria). 2016;3(8):338–51. https://doi.org/10.15698/mic2016.08.518.
Article CAS PubMed Google Scholar
Sabatini F, Petecchia L, Tavian M, Jodon de Villeroché V, Rossi GA, Brouty-Boyé D. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Investig. 2005;85(8):962–71. https://doi.org/10.1038/labinvest.3700300.
Article CAS PubMed Google Scholar
Salas A, Duarri A, Fontrodona L, Ramírez DM, Badia A, Isla-Magrané H, et al. Cell therapy with hiPSC-derived RPE cells and RPCs prevents visual function loss in a rat model of retinal degeneration. Mol Ther Methods Clin Dev. 2021;20:688–702. https://doi.org/10.1016/j.omtm.2021.02.006.
Article CAS PubMed PubMed Central Google Scholar
Saute JAM, de Castilhos RM, Monte TL, Schumacher-Schuh AF, Donis KC, D’Ávila R, et al. A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease. Mov Disord. 2014;29(4):568–73. https://doi.org/10.1002/mds.25803.
Article CAS PubMed Google Scholar
Schiess M, Suescun J, Doursout M-F, Adams C, Green C, Saltarrelli JG, et al. Allogeneic bone marrow-derived mesenchymal stem cell safety in idiopathic Parkinson’s disease. Mov Disord. 2021;36(8):1825–34. https://doi.org/10.1002/mds.28582.
Article CAS PubMed PubMed Central Google Scholar
Schmitt I, Linden M, Khazneh H, Evert BO, Breuer P, Klockgether T, Wuellner U. Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination. Biochem Biophys Res Commun. 2007;362(3):734–9. https://doi.org/10.1016/j.bbrc.2007.08.062.
Article CAS PubMed Google Scholar
Scudamore O, Ciossek T. Increased oxidative stress exacerbates α-synuclein aggregation in vivo. J Neuropathol Exp Neurol. 2018;77(6):443–53. https://doi.org/10.1093/jnen/nly024.
Article CAS PubMed Google Scholar
Shen Q, Chen B, Xiao Z, Zhao L, Xu X, Wan X, et al. Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis. Mol Med Rep. 2015;11(4):2831–7. https://doi.org/10.3892/mmr.2014.3092.
Article CAS PubMed Google Scholar
Shin JY, Park HJ, Kim HN, Oh SH, Bae J-S, Ha H-J, Lee PH. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models. Autophagy. 2014;10(1):32–44. https://doi.org/10.4161/auto.26508.
Article CAS PubMed PubMed Central Google Scholar
Sittler A, Muriel M-P, Marinello M, Brice A, den Dunnen W, Alves S. Deregulation of autophagy in postmortem brains of Machado-Joseph disease patients. Neuropathology. 2018;38(2):113–24. https://doi.org/10.1111/neup.12433.
Article CAS PubMed Google Scholar
Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol Sci. 2020;41(9):653–64. https://doi.org/10.1016/j.tips.2020.06.009.
Article CAS PubMed PubMed Central Google Scholar
Soong BW, Morrison PJ. Chapter 10: Spinocerebellar ataxias. In: Manto M, Huisman TAGM, editors. Handbook of clinical neurology, Vol. 155 (3rd series), The cerebellum disorders and treatment, vol. 155. Elsevier B.V; 2018. p. 143–74.
Chapter Google Scholar
Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer’s disease. PLoS One. 2010;5(4):e9979. https://doi.org/10.1371/journal.pone.0009979.
Article CAS PubMed PubMed Central Google Scholar
Staff NP, Jones DT, Singer W. Mesenchymal stromal cell therapies for neurodegenerative diseases. Mayo Clin Proc Mayo Clin. 2019;94(5):892–905. https://doi.org/10.1016/j.mayocp.2019.01.001.
Article PubMed Google Scholar
Stucki DM, Ruegsegger C, Steiner S, Radecke J, Murphy MP, Zuber B, Saxena S. Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ. Free Radic Biol Med. 2016;97:427–40. https://doi.org/10.1016/j.freeradbiomed.2016.07.005.
Article CAS PubMed Google Scholar
Sugiura A, Yonashiro R, Fukuda T, Matsushita N, Nagashima S, Inatome R, Yanagi S. A mitochondrial ubiquitin ligase MITOL controls cell toxicity of polyglutamine-expanded protein. Mitochondrion. 2011;11(1):139–46. https://doi.org/10.1016/j.mito.2010.09.001.
Article CAS PubMed Google Scholar
Sullivan R, Yau WY, O’Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266(2):533–44. https://doi.org/10.1007/s00415-018-9076-4.
Article PubMed Google Scholar
Sykova E, Cizkova D, Kubinova S. Mesenchymal stem cells in treatment of spinal cord injury and amyotrophic lateral sclerosis. Front Cell Dev Biol. 2021;9:695900. https://doi.org/10.3389/fcell.2021.695900.
Article PubMed PubMed Central Google Scholar
Tabera S, Pérez-Simón JA, Díez-Campelo M, Sánchez-Abarca LI, Blanco B, López A, et al. The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica. 2008;93(9):1301–9. https://doi.org/10.3324/haematol.12857.
Article CAS PubMed Google Scholar
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76. https://doi.org/10.1016/j.cell.2006.07.024.
Article CAS PubMed Google Scholar
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science (New York, NY). 1998;282(5391):1145–7. https://doi.org/10.1126/science.282.5391.1145.
Article CAS Google Scholar
Torres-Ramos Y, Montoya-Estrada A, Cisneros B, Tercero-Pérez K, León-Reyes G, Leyva-García N, et al. Oxidative stress in spinocerebellar ataxia type 7 is associated with disease severity. Cerebellum (London, England). 2018;17(5):601–9. https://doi.org/10.1007/s12311-018-0947-0.
Article CAS PubMed Google Scholar
Torres-Torrillas M, Rubio M, Damia E, Cuervo B, Del Romero A, Peláez P, et al. Adipose-derived mesenchymal stem cells: a promising tool in the treatment of musculoskeletal diseases. Int J Mol Sci. 2019;20(12):3105. https://doi.org/10.3390/ijms20123105.
Article CAS PubMed PubMed Central Google Scholar
Tsai M-S, Lee J-L, Chang Y-J, Hwang S-M. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod. 2004;19(6):1450–6. https://doi.org/10.1093/humrep/deh279.
Article PubMed Google Scholar
Tsai Y-A, Liu R-S, Lirng J-F, Yang B-H, Chang C-H, Wang Y-C, et al. Treatment of spinocerebellar ataxia with mesenchymal stem cells: a phase I/Iia clinical study. Cell Transplant. 2017;26(3):503–12. https://doi.org/10.3727/096368916X694373.
Article PubMed PubMed Central Google Scholar
Tsai M-J, Liou D-Y, Lin Y-R, Weng C-F, Huang M-C, Huang W-C, et al. Attenuating spinal cord injury by conditioned medium from bone marrow mesenchymal stem cells. J Clin Med. 2018;8(1) https://doi.org/10.3390/jcm8010023.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, NY). 2009;324(5930):1029–33. https://doi.org/10.1126/science.1160809.
Article CAS Google Scholar
Vasandan AB, Jahnavi S, Shashank C, Prasad P, Kumar A, Prasanna SJ. Human mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism. Sci Rep. 2016;6:38308. https://doi.org/10.1038/srep38308.
Article CAS PubMed PubMed Central Google Scholar
Venkataramana NK, Kumar SKV, Balaraju S, Radhakrishnan RC, Bansal A, Dixit A, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res J Lab Clin Med. 2010;155(2):62–70. https://doi.org/10.1016/j.trsl.2009.07.006.
Article CAS Google Scholar
Vercelli A, Mereuta OM, Garbossa D, Muraca G, Mareschi K, Rustichelli D, et al. Human mesenchymal stem cell transplantation extends survival, improves motor performance, and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. 2008;31(3):395–405. https://doi.org/10.1016/j.nbd.2008.05.016.
Article CAS PubMed Google Scholar
Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci. 2018;15(1):36–45. https://doi.org/10.7150/ijms.21666.
Article CAS PubMed PubMed Central Google Scholar
Volkman R, Offen D. Concise review: mesenchymal stem cells in neurodegenerative diseases. Stem Cells (Dayton, Ohio). 2017;35(8):1867–80. https://doi.org/10.1002/stem.2651.
Article PubMed Google Scholar
Wiatr K, Marczak Ł, Pérot J-B, Brouillet E, Flament J, Figiel M. Broad influence of mutant ataxin-3 on the proteome of the adult brain, young neurons, and axons reveals central molecular processes and biomarkers in SCA3/MJD using knock-in mouse model. Front Mol Neurosci. 2021;14:658339. https://doi.org/10.3389/fnmol.2021.658339.
Article CAS PubMed PubMed Central Google Scholar
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(1):63–70. https://doi.org/10.1016/j.scr.2009.02.006.
Article CAS PubMed Google Scholar
Wu Y-L, Chang J-C, Lin W-Y, Li C-C, Hsieh M, Chen H-W, et al. Treatment with caffeic acid and resveratrol alleviates oxidative stress induced neurotoxicity in cell and Drosophila models of spinocerebellar ataxia Type3. Sci Rep. 2017;7(1):11641. https://doi.org/10.1038/s41598-017-11839-0.
Article CAS PubMed PubMed Central Google Scholar
Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease—a double-edged sword. Neuron. 2002;35(3):419–32. https://doi.org/10.1016/s0896-6273(02)00794-8.
Article CAS PubMed Google Scholar
Yan Y, Jiang W, Tan Y, Zou S, Zhang H, Mao F, et al. HucMSC exosome-derived GPX1 is required for the recovery of hepatic oxidant injury. Mol Ther J Am Soc Gene Ther. 2017;25(2):465–79. https://doi.org/10.1016/j.ymthe.2016.11.019.
Article CAS Google Scholar
Ye L, Swingen C, Zhang J. Induced pluripotent stem cells and their potential for basic and clinical sciences. Curr Cardiol Rev. 2013;9(1):63–72. https://doi.org/10.2174/157340313805076278.
Article CAS PubMed PubMed Central Google Scholar
Yin F, Guo L, Meng C-Y, Liu Y-J, Lu R-F, Li P, Zhou Y-B. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury. Brain Res. 2014;1561:1–10. https://doi.org/10.1016/j.brainres.2014.02.047.
Article CAS PubMed Google Scholar
Yokokawa K, Iwahara N, Hisahara S, Emoto MC, Saito T, Suzuki H, et al. Transplantation of mesenchymal stem cells improves amyloid-β pathology by modifying microglial function and suppressing oxidative stress. J Alzheimer’s Dis. 2019;72(3):867–84. https://doi.org/10.3233/JAD-190817.
Article CAS Google Scholar
You H-J, Fang S-B, Wu T-T, Zhang H, Feng Y-K, Li X-J, et al. Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease. Stem Cell Res Ther. 2020;11(1):222. https://doi.org/10.1186/s13287-020-01727-2.
Article CAS PubMed PubMed Central Google Scholar
Yun C, Lee S. Potential and therapeutic efficacy of cell-based therapy using mesenchymal stem cells for acute/chronic kidney disease. Int J Mol Sci. 2019;20(7):1619. https://doi.org/10.3390/ijms20071619.
Article CAS PubMed PubMed Central Google Scholar
Zesiewicz TA, Greenstein PE, Sullivan KL, Wecker L, Miller A, Jahan I, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology. 2012;78(8):545–50. https://doi.org/10.1212/WNL.0b013e318247cc7a.
Article CAS PubMed Google Scholar
Zheng Z, Zhang L, Qu Y, Xiao G, Li S, Bao S, et al. Mesenchymal stem cells protect against hypoxia-ischemia brain damage by enhancing autophagy through brain derived neurotrophic factor/mammalin target of rapamycin signaling pathway. Stem Cells (Dayton, Ohio). 2018;36(7):1109–21. https://doi.org/10.1002/stem.2808.
Article CAS PubMed Google Scholar
Zhou L, Lin Q, Wang P, Yao L, Leong K, Tan Z, Huang Z. Enhanced neuroprotective efficacy of bone marrow mesenchymal stem cells co-overexpressing BDNF and VEGF in a rat model of cardiac arrest-induced global cerebral ischemia. Cell Death Dis. 2017;8(5):e2774. https://doi.org/10.1038/cddis.2017.184.
Article CAS PubMed PubMed Central Google Scholar
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211–28. https://doi.org/10.1089/107632701300062859.
Article CAS PubMed Google Scholar

Download references

Author information

Ling-Mei Wang and Bing-wen Soong contributed equally with all other contributors.

Authors and Affiliations

Steminent Biotherapeutics Inc., Taipei City, Taiwan
Chih-Yuan Ho, Hsiu-Yu Lai & Ling-Mei Wang
Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan
Bing-wen Soong
Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
Bing-wen Soong

Authors

Chih-Yuan Ho
View author publications
You can also search for this author in PubMed Google Scholar
Hsiu-Yu Lai
View author publications
You can also search for this author in PubMed Google Scholar
Ling-Mei Wang
View author publications
You can also search for this author in PubMed Google Scholar
Bing-wen Soong
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bing-wen Soong .

Editor information

Editors and Affiliations

Professor of Neurology, Shuang Ho Hospital, Taipei Medical University, Taipei, (Republic of China), Taiwan
Bing-wen Soong
Professor of Neuroanatomy, University of Mons and CHU-Charleroi, Charleroi, Belgium
Mario Manto
Paris Brain Institute, (Institut du Cerveau – ICM), CNRS INSERM, Sorbonne Université, APHP, Paris, France
Alexis Brice
Department of Neurology, Spencer Fox Eccles School of Medicine University of Utah, Salt Lake City, UT, USA
Stefan M. Pulst

Rights and permissions

Reprints and permissions

Copyright information

About this chapter

Cite this chapter

Ho, CY., Lai, HY., Wang, LM., Soong, Bw. (2023). Development of Mesenchymal Stem Cells Therapy for the Treatment of Polyglutamine SCA: From Bench to Bedside. In: Soong, Bw., Manto, M., Brice, A., Pulst, S.M. (eds) Trials for Cerebellar Ataxias. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-031-24345-5_19

Download citation

DOI: https://doi.org/10.1007/978-3-031-24345-5_19
Published: 30 May 2023
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-24344-8
Online ISBN: 978-3-031-24345-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

Publish with us

Policies and ethics