Abstract
Treatments for neurodegenerative diseases have little impact on the long-term patient health. However, cellular transplants of neuroblasts derived from the aborted embryonic brain tissue in animal models of neurodegenerative disorders and in patients have demonstrated survival and functionality in the brain. However, ethical and functional problems due to the use of this fetal tissue stopped most of the clinical trials. Therefore, new cell sources were needed, and scientists focused on neural (NSCs) and mesenchymal stem cells (MSCs). When transplanted in the brain of animals with Parkinson’s or Huntington’s disease, NSCs and MSCs were able to induce partial functional recovery by promoting neuroprotection and immunomodulation. MSCs are more readily accessible than NSCs due to sources such as the bone marrow. However, MSCs are not capable of differentiating into neurons in vivo where NSCs are. Thus, transplantation of NSCs and MSCs is interesting for brain regenerative medicine. In this chapter, we detail the methods for NSCs and MSCs isolation as well as the transplantation procedures used to treat rodent models of neurodegenerative damage.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344:710–719
Hagell P, Piccini P, Bjorklund A, Brundin P, Rehncrona S, Widner H, Crabb L, Pavese N, Oertel WH, Quinn N, Brooks DJ, Lindvall O (2002) Dyskinesias following neural transplantation in Parkinson’s disease. Nat Neurosci 5:627–628
Svendsen CN, Smith AG (1999) New prospects for human stem-cell therapy in the nervous system. Trends Neurosci 22:357–364
Vazey EM, Chen K, Hughes SM, Connor B (2006) Transplanted adult neural progenitor cells survive, differentiate and reduce motor function impairment in a rodent model of Huntington’s disease. Exp Neurol 199:384–396
Michel-Monigadon D, Bonnamain V, Nerrière-Daguin V, Dugast AS, Lévèque X, Plat M, Venturi E, Brachet P, Anegon I, Vanhove B, Neveu I, Naveilhan P (2011) Trophic and immunoregulatory properties of neural precursor cells: benefit for intracerebral transplantation. Exp Neurol 230:35–47
Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G, Martinello M, Cattalini A, Bergami A, Furlan R, Comi G, Constantin G, Martino G (2005) Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 436:266–271
Bonnamain V, Neveu I, Naveilhan P (2011) In vitro analyses of the immunosuppressive properties of neural stem/progenitor cells using anti-CD3/CD28-activated T cells. Methods Mol Biol 677:233–243
Dunbar GL, Sandstrom MI, Rossignol J, Lescaudron L (2006) Neurotrophic enhancers as therapy for behavioral deficits in rodent models of Huntington’s disease: use of gangliosides, substituted pyrimidines, and mesenchymal stem cells. Behav Cogn Neurosci Rev 5:63–79
Dey ND, Bombard MC, Roland BP, Davidson S, Lu M, Rossignol J, Sandstrom MI, Skeel RL, Lescaudron L, Dunbar GL (2010) Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington’s disease. Behav Brain Res 214:193–200
Rossignol J, Boyer C, Lévèque X, Fink KD, Thinard R, Blanchard F, Dunbar GL, Lescaudron L (2011) Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington’s disease: morphological and behavioral outcomes. Behav Brain Res 217:369–378
Rossignol J, Boyer C, Thinard R, Remy S, Dugast AS, Dubayle D, Dey ND, Boeffard F, Delecrin J, Heymann D, Vanhove B, Anegon I, Naveilhan P, Dunbar GL, Lescaudron L (2009) Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation. J Cell Mol Med 13:2547–2558
Michel DC, Nerrière-Daguin V, Josien R, Brachet P, Naveilhan P, Neveu I (2006) Dendritic cell recruitment following xenografting of pig fetal mesencephalic cells into the rat brain. Exp Neurol 202:76–84
von Hörsten S, Schmitt I, Nguyen HP, Holzmann C, Schmidt T, Walther T, Bader M, Pabst R, Kobbe P, Krotova J, Stiller D, Kask A, Vaarmann A, Rathke-Hartlieb S, Schulz JB, Grasshoff U, Bauer I, Vieira-Saecker AM, Paul M, Jones L, Lindenberg KS, Landwehrmeyer B, Bauer A, Li XJ, Riess O (2003) Transgenic rat model of Huntington’s disease. Hum Mol Genet 12:617–624
Lelan F, Boyer C, Thinard R, Rémy S, Usal C, Tesson L, Anegon I, Neveu I, Damier P, Naveilhan P, Lescaudron L (2011) Effects of human alpha-synuclein A53T-A30P mutations on SVZ and local olfactory bulb cell proliferation in a transgenic rat model of Parkinson disease. Parkinsons Dis 2011:987084
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Buadze M, Geisler J, Klopfer T, Burkhardt U, Proksch B, Verleysdonk S, Ayturan M, Buniatian GH, Gleiter CH, Frey WH 2nd (2009) Intranasal delivery of cells to the brain. Eur J Cell Biol 88:315–324
Acknowledgments
The nestin monoclonal antibody developed by Susan Hockfield was obtained from the Developmental Studies Hybridoma Bank. This work was supported by the “Association Française contre les Myopathies” (AFM-France), the “Fédération des Groupements de Parkinsoniens-CECAP-France,” L’Association Huntington France, and Progreffe Foundation (INSERM U643).
D. Michel-Monigadon and F. Lelan were supported during their Ph.D. thesis by INSERM/Région Pays de la Loire. V. Bonnamain and Julien Rossignol were supported during their Ph.D. thesis by the Ministère de l’Enseignement Supérieur et de la Recherche and from Progreffe Foundation.
Xavier Lévêque was supported by the University of Nantes during his postdoctoral stay. Gary Dunbar was supported by the Field Neurosciences Institute and John G. Kulhavi Professorship. All members of CMU were also supported by the Field Neurosciences Institute.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Lescaudron, L. et al. (2012). Assessing the Potential Clinical Utility of Transplantations of Neural and Mesenchymal Stem Cells for Treating Neurodegenerative Diseases. In: Singh, S. (eds) Somatic Stem Cells. Methods in Molecular Biology, vol 879. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-815-3_10
Download citation
DOI: https://doi.org/10.1007/978-1-61779-815-3_10
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-814-6
Online ISBN: 978-1-61779-815-3
eBook Packages: Springer Protocols