Skip to main content

Advertisement

SpringerLink
Log in

Midbrain-derived neural stem cells: from basic science to therapeutic approaches

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Neural stem cells (NSCs) are a subtype of tissue-specific progenitor cells capable of extended self-renewal and the ability to generate all major cell types of nervous tissue, such as neurons, astroglia and oligodendroglial cells. Recent studies suggest that salient patterning in anterior–posterior and dorsal–ventral axes occurs early, concomitantly with neural induction and therefore stem cells and restricted precursors exhibit regionalization. Fetal mesencephalic NSCs can be isolated and expanded in vitro for many months while retaining their potential to differentiate into glia and neurons, with a subset of neurons displaying all the major properties of mature functional dopaminergic neurons. Since Parkinson’s disease (PD) is characterized by the loss of a specific type of dopaminergic cells, the prospect of replacing the missing or damaged cells is very attractive in PD. Thus, mesencephalic NSCs might serve as a new and continuous source of dopaminergic neurons for regenerative strategies in this neurodegenerative disorder. This review discusses new data concerning the cell biology and therapeutic potential of NSCs derived from the midbrain region of the central nervous system.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, Snyder EY (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97:12846–12851

    Article  CAS  PubMed  Google Scholar 

  • Akerud P, Holm PC, Castelo-Branco G, Sousa K, Rodriguez FJ, Arenas E (2002) Persephin-overexpressing neural stem cells regulate the function of nigral dopaminergic neurons and prevent their degeneration in a model of Parkinson’s disease. Mol Cell Neurosci 21:205–222

    Article  CAS  PubMed  Google Scholar 

  • Akiyama Y, Honmou O, Kato T, Uede T, Hashi K, Kocsis JD (2001) Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord. Exp Neurol 167:27–39

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Buylla A, Garcia-Verdugo JM, Mateo AS, Merchant-Larios H (1998) Primary neural precursors and intermitotic nuclear migration in the ventricular zone of adult canaries. J Neurosci 18:1020–1037

    CAS  PubMed  Google Scholar 

  • Alvarez-Buylla A, Seri B, Doetsch F (2002) Identification of neural stem cells in the adult vertebrate brain. Brain Res Bull 57:751–758

    Article  PubMed  Google Scholar 

  • Arsenijevic Y, Villemure JG, Brunet JF, Bloch JJ, Deglon N, Kostic C, Zurn A, Aebischer P (2001) Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Exp Neurol 170:48–62

    Article  CAS  PubMed  Google Scholar 

  • Aubert J, Stavridis MP, Tweedie S, O’Reilly M, Vierlinger K, Li M, Ghazal P, Pratt T, Mason JO, Roy D, Smith A (2003) Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knockin mice. Proc Natl Acad Sci USA 100 (Suppl 1):11836–11841

    Article  CAS  PubMed  Google Scholar 

  • Bain G, Kitchens D, Yao M, Huettner JE, Gottlieb DI (1995) Embryonic stem cells express neuronal properties in vitro. Dev Biol 168:342–357

    Article  CAS  PubMed  Google Scholar 

  • Bjorklund A, Dunnett SB, Brundin P, Stoessl AJ, Freed CR, Breeze RE, Levivier M, Peschanski M, Studer L, Barker R (2003) Neural transplantation for the treatment of Parkinson’s disease. Lancet Neurol 2:437–445

    Article  PubMed  Google Scholar 

  • Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 99:2344–2349

    Article  CAS  PubMed  Google Scholar 

  • Buccellato LJ, Tso M, Akinci OI, Chandel NS, Budinger GR (2004) Reactive oxygen species are required for hyperoxia-induced bax activation and cell death in alveolar epithelial cells. J Biol Chem 279:6753–6760

    Article  CAS  PubMed  Google Scholar 

  • Budinger GR, Tso M, McClintock DS, Dean DA, Sznajder JI, Chandel NS (2002) Hyperoxia-induced apoptosis does not require mitochondrial reactive oxygen species and is regulated by Bcl-2 proteins. J Biol Chem 277:15654–15660

    Article  CAS  PubMed  Google Scholar 

  • Cai J, Limke TL, Ginis I, Rao MS (2003) Identifying and tracking neural stem cells. Blood Cells Mol Dis 31:18–27

    Article  CAS  PubMed  Google Scholar 

  • Caldwell MA, Svendsen CN (1998) Heparin, but not other proteoglycans potentiates the mitogenic effects of FGF-2 on mesencephalic precursor cells. Exp Neurol 152:1–10

    Article  CAS  PubMed  Google Scholar 

  • Carvey PM, Ling ZD, Sortwell CE, Pitzer MR, McGuire SO, Storch A, Collier TJ (2001) A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson’s disease. Exp Neurol 171:98–108

    Article  CAS  PubMed  Google Scholar 

  • Cattaneo E, McKay R (1990) Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature 347:762–765

    Article  CAS  PubMed  Google Scholar 

  • Chase TN, Oh JD (2000) Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. Ann Neurol 47:S122–S129

    Article  CAS  PubMed  Google Scholar 

  • Csete M, Walikonis J, Slawny N, Wei Y, Korsnes S, Doyle JC, Wold B (2001) Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture. J Cell Physiol 189:189–196

    Article  CAS  PubMed  Google Scholar 

  • Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716

    Article  CAS  PubMed  Google Scholar 

  • Dunnett SB, Bjorklund A (1999) Prospects for new restorative and neuroprotective treatments in Parkinson’s disease. Nature 399:A32–A39

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Gaiano N, Fishell G (1998) Transplantation as a tool to study progenitors within the vertebrate nervous system. J Neurobiol 36:152–161

    Article  CAS  PubMed  Google Scholar 

  • Gensburger C, Labourdette G, Sensenbrenner M (1987) Brain basic fibroblast growth factor stimulates the proliferation of rat neuronal precursor cells in vitro. FEBS Lett 217:1–5

    Article  CAS  PubMed  Google Scholar 

  • Golusinski W, Olofsson J, Szmeja Z, Biczysko W, Krygier-Stojalowska A, Kulczynski B (1999) A comprehensive analysis of selected diagnostic methods with respect to their usefulness in evaluating the biology of neoplastic cells in patients with laryngeal cancer. Eur Arch Otorhinolaryngol 256:306–311

    Article  CAS  PubMed  Google Scholar 

  • Gritti A, Bonfanti L, Doetsch F, Caille I, Alvarez-Buylla A, Lim DA, Galli R, Verdugo JM, Herrera DG, Vescovi AL (2002) Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. J Neurosci 22:437–445

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Haque NS, LeBlanc CJ, Isacson O (1997) Differential dissection of the rat E16 ventral mesencephalon and survival and reinnervation of the 6-OHDA-lesioned striatum by a subset of aldehyde dehydrogenase-positive TH neurons. Cell Transplant 6:239–248

    Article  CAS  PubMed  Google Scholar 

  • Hayashi T, Uchida K, Mine Y, Yamada M, Kawase T (2002) Feasibility of using early mesencephalic neural plate for intracerebral grafting. Cell Transplant 11:465–470

    PubMed  Google Scholar 

  • Hermann A, Gerlach M, Schwarz J, Storch A (2004a) Neurorestoration in Parkinson’s disease by cell replacement and endogenous regeneration. Expert Opin Biol Ther 4:131–143

    Article  PubMed  Google Scholar 

  • Hermann A, Gastl R, Liebau S, Popa MO, Fiedler J, Boehm BO, Maisel M, Lerche H, Schwarz J, Brenner RE, Storch A (2004b) Efficient generation of neural stem cell like cells from adult human bone marrow stromal cells. J Cell Sci (in press)

  • Hurelbrink CB, Armstrong RJ, Dunnett SB, Rosser AE, Barker RA (2002) Neural cells from primary human striatal xenografts migrate extensively in the adult rat CNS. Eur J Neurosci 15:1255–1266

    Article  PubMed  Google Scholar 

  • Kawasaki H, Mizuseki K, Nishikawa S, Kaneko S, Kuwana Y, Nakanishi S, Nishikawa S, Sasai Y (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28:31–40

    Article  CAS  PubMed  Google Scholar 

  • Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa S, Nakatsuji N, Sasai Y (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell derived inducing activity. Proc Natl Acad Sci USA 99:1580–1585

    Article  CAS  PubMed  Google Scholar 

  • Kay JN, Blum M (2000) Differential response of ventral midbrain and striatal progenitor cells to lesions of the nigrostriatal dopaminergic projection. Dev Neurosci 22:56–67

    Article  CAS  PubMed  Google Scholar 

  • Kilpatrick TJ, Bartlett PF (1993) Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. Neuron 10:255–265

    CAS  PubMed  Google Scholar 

  • Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, Koh HC, Lee JY, Chang MY, Kim YC, Chung HY, Son H, Lee YS, Studer L, McKay R, Lee SH (2003) Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression. J Neurochem 85:1443–1454

    Article  CAS  PubMed  Google Scholar 

  • Kim TE, Lee HS, Lee YB, Hong SH, Lee YS, Ichinose H, Kim SU, Lee MA (2003) Sonic hedgehog and FGF8 collaborate to induce dopaminergic phenotypes in the Nurr1-overexpressing neural stem cell. Biochem Biophys Res Commun 305:1040–1048

    Article  CAS  PubMed  Google Scholar 

  • Kitayama T, Yoneyama M, Yoneda Y (2003) Possible regulation by N-methyl-daspartate receptors of proliferative progenitor cells expressed in adult mouse hippocampal dentate gyrus. J Neurochem 84:767–780

    Article  CAS  PubMed  Google Scholar 

  • Kukekov VG, Laywell ED, Thomas LB, Steindler DA (1997) A nestin-negative precursor cell from the adult mouse brain gives rise to neurons and glia. Glia 21:399–407

    Article  CAS  PubMed  Google Scholar 

  • Lang AE, Lozano AM (1998a) Parkinson’s disease. Second of two parts. N Engl J Med 339:1130–1143

    Article  CAS  PubMed  Google Scholar 

  • Lang AE, Lozano AM (1998b) Parkinson’s disease. First of two parts. N Engl J Med 339:1044–1053

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD (2000) Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 18:675–679

    Article  CAS  PubMed  Google Scholar 

  • Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW, Gage FH (2002) The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22:6639–6649

    CAS  PubMed  Google Scholar 

  • Lie DC, Song H, Colamarino SA, Ming GL, Gage FH (2004) Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol 44:399–421

    Article  CAS  PubMed  Google Scholar 

  • Ling ZD, Potter ED, Lipton JW, Carvey PM (1998) Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp Neurol 149:411–423

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Serrano A, Bjorklund A (1997) Immortalized neural progenitor cells for CNS gene transfer and repair. Trends Neurosci 20:530–538

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Serrano A, Lundberg C, Horellou P, Fischer W, Bentlage C, Campbell K, McKay RD, Mallet J, Bjorklund A (1995) CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: complete rescue of axotomized cholinergic neurons after transplantation into the septum. J Neurosci 15:5668–5680

    CAS  PubMed  Google Scholar 

  • Matunis MJ (2002) On the road to repair: PCNA encounters SUMO and ubiquitin modifications. Mol Cell 10:441–442

    Article  CAS  PubMed  Google Scholar 

  • Mayer-Proschel M, Kalyani AJ, Mujtaba T, Rao MS (1997) Isolation of lineage restricted neuronal precursors from multipotent neuroepithelial stem cells. Neuron 19:773–785

    Article  CAS  PubMed  Google Scholar 

  • Milosevic J, Storch A, Schwarz J (2004) Spontaneous apoptosis in murine free-floating neurospheres. Exp Cell Res 294:9–17

    Article  CAS  PubMed  Google Scholar 

  • Morrison SJ, Csete M, Groves AK, Melega W, Wold B, Anderson DJ (2000) Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. J Neurosci 20:7370–7376

    CAS  PubMed  Google Scholar 

  • Neubauer JA, Sunderram J (2004) Oxygen-sensing neurons in the central nervous system. J Appl Physiol 96:367–374

    Article  CAS  PubMed  Google Scholar 

  • Nishino H, Hida H, Takei N, Kumazaki M, Nakajima K, Baba H (2000) Mesencephalic neural stem (progenitor) cells develop to dopaminergic neurons more strongly in dopamine-depleted striatum than in intact striatum. Exp Neurol 164:209–214

    Article  CAS  PubMed  Google Scholar 

  • Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54:403–414

    Article  PubMed  Google Scholar 

  • Ostenfeld T, Tai YT, Martin P, Deglon N, Aebischer P, Svendsen CN (2002) Neurospheres modified to produce glial cell line-derived neurotrophic factor increase the survival of transplanted dopamine neurons. J Neurosci Res 69:955–965

    Article  CAS  PubMed  Google Scholar 

  • Ourednik J, Ourednik V, Lynch WP, Schachner M, Snyder EY (2002) Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat Biotechnol 20:1103–1110

    Article  CAS  PubMed  Google Scholar 

  • Palmer TD, Ray J, Gage FH (1995) FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain. Mol Cell Neurosci 6:474–486

    Article  CAS  PubMed  Google Scholar 

  • Perrone-Capano C, Di Porzio U (2000) Genetic and epigenetic control of midbrain dopaminergic neuron development. Int J Dev Biol 44:679–687

    CAS  PubMed  Google Scholar 

  • Potter ED, Ling ZD, Carvey PM (1999) Cytokine-induced conversion of mesencephalic-derived progenitor cells into dopamine neurons. Cell Tissue Res 296:235–246

    Article  CAS  PubMed  Google Scholar 

  • Rao MS, Mayer-Proschel M (1997) Glial-restricted precursors are derived from multipotent neuroepithelial stem cells. Dev Biol 188:48–63

    Article  CAS  PubMed  Google Scholar 

  • Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    CAS  PubMed  Google Scholar 

  • Riaz SS, Jauniaux E, Stern GM, Bradford HF (2002) The controlled conversion of human neural progenitor cells derived from foetal ventral mesencephalon into dopaminergic neurons in vitro. Brain Res Dev Brain Res 136:27–34

    Article  CAS  PubMed  Google Scholar 

  • Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF (2001) Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 412:736–739

    Article  CAS  PubMed  Google Scholar 

  • Rossi F, Cattaneo E (2002) Opinion: neural stem cell therapy for neurological diseases: dreams and reality. Nat Rev Neurosci 3:401–409

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Pernaute R, Studer L, Bankiewicz KS, Major EO, McKay RD (2001) In vitro generation and transplantation of precursor-derived human dopamine neurons. J Neurosci Res 65:284–288

    Article  CAS  PubMed  Google Scholar 

  • Sawamoto K, Nakao N, Kakishita K, Ogawa Y, Toyama Y, Yamamoto A, Yamaguchi M, Mori K, Goldman SA, Itakura T, Okano H (2001) Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene. J Neurosci 21:3895–3903

    CAS  PubMed  Google Scholar 

  • Selander L, Edlund H (2002) Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev 113:189–192

    Article  CAS  PubMed  Google Scholar 

  • Sharpless NE, DePinho RA (2004) Telomeres, stem cells, senescence, and cancer. J Clin Invest 113:160–168

    Article  CAS  PubMed  Google Scholar 

  • Silver I, Erecinska M (1998) Oxygen and ion concentrations in normoxic and hypoxic brain cells. Adv Exp Med Biol 454:7–16

    CAS  PubMed  Google Scholar 

  • Snyder EY, Flax JD (1995) Transplantation of neural progenitors or stem-like cells as a strategy for gene therapy and repair of neurodegenerative diseases. Ment Retard Dev Disabil Res Rev 1:27–38

    Google Scholar 

  • Starborg M, Gell K, Brundell E, Hoog C (1996) The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression. J Cell Sci 109:143–153

    CAS  PubMed  Google Scholar 

  • Storch A, Paul G, Csete M, Boehm BO, Carvey PM, Kupsch A, Schwarz J (2001) Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp Neurol 170:317–325

    Article  CAS  PubMed  Google Scholar 

  • Storch A, Lester HA, Boehm BO, Schwarz J (2003) Functional characterization of dopaminergic neurons derived from rodent mesencephalic progenitor cells. J Chem Neuroanat 26:133–142

    Article  CAS  PubMed  Google Scholar 

  • Studer L, Tabar V, McKay RD (1998) Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat Neurosci 1:290–295

    Article  CAS  PubMed  Google Scholar 

  • Studer L, Csete M, Lee SH, Kabbani N, Walikonis J, Wold B, McKay R (2000) Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 20:7377–7383

    CAS  PubMed  Google Scholar 

  • Sun ZH, Lai YL, Zeng WW, Zhao D, Zuo HC, Xie ZP (2003a) Neural stem/progenitor cells survive and differentiate better in PD rats than in normal rats. Acta Neurochir Suppl 87:169–174

    CAS  PubMed  Google Scholar 

  • Sun ZH, Lai YL, Zeng WW, Zhao D, Ye ZW, Zuo HC, Xie ZP (2003b) Mesencephalic progenitors can improve rotational behavior and reconstruct nigrostriatal pathway in PD rats. Acta Neurochir Suppl 87:175–180

    CAS  PubMed  Google Scholar 

  • Svendsen CN, Clarke DJ, Rosser AE, Dunnett SB (1996) Survival and differentiation of rat and human epidermal growth factor-responsive precursor cells following grafting into the lesioned adult central nervous system. Exp Neurol 137:376–388

    Article  CAS  PubMed  Google Scholar 

  • Svendsen CN, Caldwell MA, Shen J, Borg MG ter, Rosser AE, Tyers P, Karmiol S, Dunnett SB (1997) Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson’s disease. Exp Neurol 148:135–146

    Article  CAS  PubMed  Google Scholar 

  • Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97:14720–14725

    Article  CAS  PubMed  Google Scholar 

  • Vescovi AL, Snyder EY (1999) Establishment and properties of neural stem cell clones: plasticity in vitro and in vivo. Brain Pathol 9:569–598

    CAS  PubMed  Google Scholar 

  • Vescovi AL, Gritti A, Galli R, Parati EA (1999a) Isolation and intracerebral grafting of nontransformed multipotential embryonic human CNS stem cells. J Neurotrauma 16:689–693

    CAS  PubMed  Google Scholar 

  • Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, Frolichsthal-Schoeller P, Cova L, Arcellana-Panlilio M, Colombo A, Galli R (1999b) Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 156:71–83

    Article  CAS  PubMed  Google Scholar 

  • Vogel W, Grunebach F, Messam CA, Kanz L, Brugger W, Buhring HJ (2003) Heterogeneity among human bone marrow-derived mesenchymal stem cells and neural progenitor cells. Haematologica 88:126–133

    PubMed  Google Scholar 

  • Wagner J, Akerud P, Castro DS, Holm PC, Canals JM, Snyder EY, Perlmann T, Arenas E (1999) Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Nat Biotechnol 17:653–659

    Article  CAS  PubMed  Google Scholar 

  • Wenger RH (2002) Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. Fed Am Soc Exp Biol J 16:1151–1162

    Article  CAS  Google Scholar 

  • Whittemore SR, Morassutti DJ, Walters WM, Liu RH, Magnuson DS (1999) Mitogen and substrate differentially affect the lineage restriction of adult rat subventricular zone neural precursor cell populations. Exp Cell Res 252:75–95

    Article  CAS  PubMed  Google Scholar 

  • Ye W, Shimamura K, Rubenstein JL, Hynes MA, Rosenthal A (1998) FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93:755–766

    Article  CAS  PubMed  Google Scholar 

  • Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM (2003) Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci USA 100:7925–7930

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

    Alexander Storch

  2. Department of Neurology, University of Ulm, 89081, Ulm, Germany

    Alexander Storch & Michael Sabolek

  3. Department of Neurology, University of Leipzig, 04103, Leipzig, Germany

    Javorina Milosevic & Johannes Schwarz

  4. NeuroProgen GmbH, Leipzig, Germany

    Sigrid C. Schwarz

Authors
  1. Alexander Storch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Sabolek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Javorina Milosevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sigrid C. Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Johannes Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander Storch.

Additional information

The work of the authors was supported in part by the Interdisziplinäres Zentrum für klinische Forschung (IZKF) Ulm (Project D6) to A.S., the BMBF (Polish-German Cooperation in Neuroscience Program) to A.S., the Ministerium für Wissenschaft und Kultur Baden-Württemberg (Landesforschungsschwerpunkt “Neurodegeneration und Neuroregeneration”) to A.S., and the Landesstiftung Baden-Württemberg (Förderprogramm “Adulte Stammzellen”) to A.S. M.S. was supported by a fellowship from the IZKF Ulm

Rights and permissions

Reprints and permissions

About this article

Cite this article

Storch, A., Sabolek, M., Milosevic, J. et al. Midbrain-derived neural stem cells: from basic science to therapeutic approaches. Cell Tissue Res 318, 15–22 (2004). https://doi.org/10.1007/s00441-004-0923-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-004-0923-5

Keywords

Search

Navigation