Skip to main content

Advertisement

Log in

Cell-based therapy for stroke

  • Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Current treatments for stroke, such as the use of thrombolytic agents, are often limited by a narrow therapeutic time window. However, the regeneration of the brain after damage is still active days even weeks after stroke occurs, which might provide a second window for treatment. Cell-based therapy can be categorized into two strategies. One is transplantation of exogenous cells into the injured brain to replace the lost cells or support the remaining cells. The other strategy is to enhance the proliferation, differentiation, migration of endogenous stem or progenitor cells. Recent development in adult stem cell research and advancement in the induction of pluripotent stem cells from somatic adult cells provide a tremendous opportunity for transplantation therapy. Understanding the mechanisms and regulations involved in the endogenous neurogenesis will also help develop novel therapeutic interventions to promote neurogenesis and functional recovery in stroke. This review describes up-to-date progresses in cell-based therapy for the treatment of stroke.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC (1997) The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 185:111–120

    CAS  PubMed  Google Scholar 

  • Alvarez-Buylla A, Lim DA (2004) For the long run: maintaining germinal niches in the adult brain. Neuron 41:683–686

    CAS  PubMed  Google Scholar 

  • Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, Paz N, Koren-Michowitz M, Waldman D, Leider-Trejo L et al (2009) Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6:e1000029

    PubMed  Google Scholar 

  • Andres RH, Choi R, Steinberg GK, Guzman R (2008a) Potential of adult neural stem cells in stroke therapy. Regen Med 3:893–905

    PubMed  Google Scholar 

  • Andres RH, Guzman R, Ducray AD, Mordasini P, Gera A, Barth A, Widmer HR, Steinberg GK (2008b) Cell replacement therapy for intracerebral hemorrhage. Neurosurg Focus 24:E16

    PubMed  Google Scholar 

  • Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442:823–826

    CAS  PubMed  Google Scholar 

  • Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970

    CAS  PubMed  Google Scholar 

  • Battler A, Leor J (2006) Stem cell and gene-based therapy: frontiers in regenerative medicine. Springer, London

    Google Scholar 

  • Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA (2001) Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci 21:6718–6731

    CAS  PubMed  Google Scholar 

  • Bjorklund A (2000) Cell replacement strategies for neurodegenerative disorders. Novartis Found Symp 231:7–15 (discussion 16–20)

    CAS  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

    CAS  PubMed  Google Scholar 

  • Bliss T, Guzman R, Daadi M, Steinberg GK (2007) Cell transplantation therapy for stroke. Stroke 38:817–826

    PubMed  Google Scholar 

  • Borlongan CV, Hadman M, Sanberg CD, Sanberg PR (2004) Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke. Stroke 35:2385–2389

    PubMed  Google Scholar 

  • Cajal Ry (1928) Studies on the degeneration and regeneration of the nervous system. Oxford University Press, Oxford

    Google Scholar 

  • Chalimoniuk M, Strosznajder JB (1998) Aging modulates nitric oxide synthesis and cGMP levels in hippocampus and cerebellum. Effects of amyloid beta peptide. Mol Chem Neuropathol 35:77–95

    CAS  PubMed  Google Scholar 

  • Chang YC, Shyu WC, Lin SZ, Li H (2007) Regenerative therapy for stroke. Cell Transplant 16:171–181

    PubMed  Google Scholar 

  • Chen J, Li Y, Wang L, Lu M, Zhang X, Chopp M (2001a) Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J Neurol Sci 189:49–57

    CAS  PubMed  Google Scholar 

  • Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001b) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011

    CAS  PubMed  Google Scholar 

  • Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, Lu M, Zhu Z, Chopp M (2003) Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 92:692–699

    CAS  PubMed  Google Scholar 

  • Chopp M, Li Y (2008) Treatment of stroke and intracerebral hemorrhage with cellular and pharmacological restorative therapies. Acta Neurochir Suppl 105:79–83

    CAS  PubMed  Google Scholar 

  • Conover JC, Doetsch F, Garcia-Verdugo JM, Gale NW, Yancopoulos GD, Alvarez-Buylla A (2000) Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat Neurosci 3:1091–1097

    CAS  PubMed  Google Scholar 

  • Corbin JD, Francis SH (1999) Cyclic GMP phosphodiesterase-5: target of sildenafil. J Biol Chem 274:13729–13732

    CAS  PubMed  Google Scholar 

  • Coyne TM, Marcus AJ, Woodbury D, Black IB (2006) Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 24:2483–2492

    PubMed  Google Scholar 

  • Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, van der Kooy D (1996) In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain. J Neurosci 16:2649–2658

    CAS  PubMed  Google Scholar 

  • Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C et al (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243–1249

    CAS  PubMed  Google Scholar 

  • Dar A, Kollet O, Lapidot T (2006) Mutual, reciprocal SDF-1/CXCR4 interactions between hematopoietic and bone marrow stromal cells regulate human stem cell migration and development in NOD/SCID chimeric mice. Exp Hematol 34:967–975

    CAS  PubMed  Google Scholar 

  • Deacon T, Dinsmore J, Costantini LC, Ratliff J, Isacson O (1998) Blastula-stage stem cells can differentiate into dopaminergic and serotonergic neurons after transplantation. Exp Neurol 149:28–41

    CAS  PubMed  Google Scholar 

  • Dempsey RJ, Sailor KA, Bowen KK, Tureyen K, Vemuganti R (2003) Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain: effect of exogenous IGF-1 and GDNF. J Neurochem 87:586–597

    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

    CAS  PubMed  Google Scholar 

  • Doss MX, Koehler CI, Gissel C, Hescheler J, Sachinidis A (2004) Embryonic stem cells: a promising tool for cell replacement therapy. J Cell Mol Med 8:465–473

    PubMed  Google Scholar 

  • Doucette JR (1984) The glial cells in the nerve fiber layer of the rat olfactory bulb. Anat Rec 210:385–391

    CAS  PubMed  Google Scholar 

  • Doucette R (1995) Olfactory ensheathing cells: potential for glial cell transplantation into areas of CNS injury. Histol Histopathol 10:503–507

    CAS  PubMed  Google Scholar 

  • Englund U, Bjorklund A, Wictorin K, Lindvall O, Kokaia M (2002) Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry. Proc Natl Acad Sci USA 99:17089–17094

    CAS  PubMed  Google Scholar 

  • Erdo F, Buhrle C, Blunk J, Hoehn M, Xia Y, Fleischmann B, Focking M, Kustermann E, Kolossov E, Hescheler J et al (2003) Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J Cereb Blood Flow Metab 23:780–785

    PubMed  Google Scholar 

  • Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317

    CAS  PubMed  Google Scholar 

  • Eriksson M, Norrving B, Terent A, Stegmayr B (2008) Functional outcome 3 months after stroke predicts long-term survival. Cerebrovasc Dis 25:423–429

    PubMed  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    CAS  PubMed  Google Scholar 

  • Fallon J, Reid S, Kinyamu R, Opole I, Opole R, Baratta J, Korc M, Endo TL, Duong A, Nguyen G et al (2000) In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci USA 97:14686–14691

    CAS  PubMed  Google Scholar 

  • Feron F, Perry C, Cochrane J, Licina P, Nowitzke A, Urquhart S, Geraghty T, Mackay-Sim A (2005) Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 128:2951–2960

    CAS  PubMed  Google Scholar 

  • Gilman S (2006) Pharmacologic management of ischemic stroke: relevance to stem cell therapy. Exp Neurol 199:28–36

    CAS  PubMed  Google Scholar 

  • Goldstein LB (2007) Acute ischemic stroke treatment in 2007. Circulation 116:1504–1514

    PubMed  Google Scholar 

  • Gould E (2007) How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 8:481–488

    CAS  PubMed  Google Scholar 

  • Grabowski M, Johansson BB, Brundin P (1994) Survival of fetal neocortical grafts implanted in brain infarcts of adult rats: the influence of postlesion time and age of donor tissue. Exp Neurol 127:126–136

    CAS  PubMed  Google Scholar 

  • Grompe M (2002) Adult versus embryonic stem cells: it’s still a tie. Mol Ther 6:303–305

    CAS  PubMed  Google Scholar 

  • Grote HE, Hannan AJ (2007) Regulators of adult neurogenesis in the healthy and diseased brain. Clin Exp Pharmacol Physiol 34:533–545

    CAS  PubMed  Google Scholar 

  • Guerra-Crespo M, Gleason D, Sistos A, Toosky T, Solaroglu I, Zhang JH, Bryant PJ, Fallon JH (2009) Transforming growth factor-alpha induces neurogenesis and behavioral improvement in a chronic stroke model. Neuroscience 160:470–483

    CAS  PubMed  Google Scholar 

  • Hakim AM (1998) Ischemic penumbra: the therapeutic window. Neurology 51:S44–S46

    CAS  PubMed  Google Scholar 

  • Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh JH, Hackett NR, Quitoriano MS, Crystal RG, Rafii S, Moore MA (2001) Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 97:3354–3360

    CAS  PubMed  Google Scholar 

  • Hattori K, Heissig B, Rafii S (2003) The regulation of hematopoietic stem cell and progenitor mobilization by chemokine SDF-1. Leuk Lymphoma 44:575–582

    CAS  PubMed  Google Scholar 

  • Hicks AU, Hewlett K, Windle V, Chernenko G, Ploughman M, Jolkkonen J, Weiss S, Corbett D (2007) Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke. Neuroscience 146:31–40

    CAS  PubMed  Google Scholar 

  • Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK et al (2002) Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci USA 99:16267–16272

    CAS  PubMed  Google Scholar 

  • Hoglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, Hirsch EC (2004) Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 7:726–735

    PubMed  Google Scholar 

  • Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA et al (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101:18117–18122

    CAS  PubMed  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49

    CAS  PubMed  Google Scholar 

  • Jiang Q, Zhang ZG, Ding GL, Zhang L, Ewing JR, Wang L, Zhang R, Li L, Lu M, Meng H et al (2005) Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI. Neuroimage 28:698–707

    PubMed  Google Scholar 

  • Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 99:11946–11950

    CAS  PubMed  Google Scholar 

  • Johnston RE, Dillon-Carter O, Freed WJ, Borlongan CV (2001) Trophic factor secreting kidney cell lines: in vitro characterization and functional effects following transplantation in ischemic rats. Brain Res 900:268–276

    CAS  PubMed  Google Scholar 

  • Jordan JD, Ming GL, Song H (2006) Adult neurogenesis as a potential therapy for neurodegenerative diseases. Discov Med 6:144–147

    PubMed  Google Scholar 

  • Kameda M, Shingo T, Takahashi K, Muraoka K, Kurozumi K, Yasuhara T, Maruo T, Tsuboi T, Uozumi T, Matsui T et al (2007) Adult neural stem and progenitor cells modified to secrete GDNF can protect, migrate and integrate after intracerebral transplantation in rats with transient forebrain ischemia. Eur J Neurosci 26:1462–1478

    CAS  PubMed  Google Scholar 

  • Kobayashi T, Ahlenius H, Thored P, Kobayashi R, Kokaia Z, Lindvall O (2006) Intracerebral infusion of glial cell line-derived neurotrophic factor promotes striatal neurogenesis after stroke in adult rats. Stroke 37:2361–2367

    CAS  PubMed  Google Scholar 

  • Kolb B, Morshead C, Gonzalez C, Kim M, Gregg C, Shingo T, Weiss S (2007) Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J Cereb Blood Flow Metab 27:983–997

    CAS  PubMed  Google Scholar 

  • Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J, Ratajczak MZ (2006) A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia 20:857–869

    CAS  PubMed  Google Scholar 

  • Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17:5820–5829

    CAS  PubMed  Google Scholar 

  • Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Ishii K, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y et al (2005) Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther 11:96–104

    CAS  PubMed  Google Scholar 

  • Li Y, Chen J, Wang L, Lu M, Chopp M (2001) Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 56:1666–1672

    CAS  PubMed  Google Scholar 

  • Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N, Chopp M (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:514–523

    CAS  PubMed  Google Scholar 

  • Li L, Jiang Q, Zhang L, Ding G, Wang L, Zhang R, Zhang ZG, Li Q, Ewing JR, Kapke A et al (2006) Ischemic cerebral tissue response to subventricular zone cell transplantation measured by iterative self-organizing data analysis technique algorithm. J Cereb Blood Flow Metab 26:1366–1377

    PubMed  Google Scholar 

  • Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, Gage FH (2005) Wnt signalling regulates adult hippocampal neurogenesis. Nature 437:1370–1375

    CAS  PubMed  Google Scholar 

  • Lima C, Pratas-Vital J, Escada P, Hasse-Ferreira A, Capucho C, Peduzzi JD (2006) Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med 29:191–203 (discussion 204–206)

    PubMed  Google Scholar 

  • Lindvall O, Kokaia Z, Martinez-Serrano A (2004) Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med 10(Suppl):S42–S50

    PubMed  Google Scholar 

  • Liu J, Solway K, Messing RO, Sharp FR (1998) Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 18:7768–7778

    CAS  PubMed  Google Scholar 

  • Llado J, Haenggeli C, Maragakis NJ, Snyder EY, Rothstein JD (2004) Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors. Mol Cell Neurosci 27:322–331

    CAS  PubMed  Google Scholar 

  • Luo Y, Kuo C-C, Shen H, Chou J, Greig NH, Hoffer BJ, Wang Y (2009) Delayed treatment with a p53 inhibitor enhances recovery in stroke brain. Annals of Neurology 9999, NA

  • Ma YP, Ma MM, Ge S, Guo RB, Zhang HJ, Frey WH 2nd, Xu GL, Liu XF (2007) Intranasally delivered TGF-beta1 enters brain and regulates gene expressions of its receptors in rats. Brain Res Bull 74:271–277

    CAS  PubMed  Google Scholar 

  • Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME, Henn F, Benveniste H, Djuric PM, Enikolopov G, Maletic-Savatic M (2007) Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318:980–985

    CAS  PubMed  Google Scholar 

  • Matthys P, Hatse S, Vermeire K, Wuyts A, Bridger G, Henson GW, De Clercq E, Billiau A, Schols D (2001) AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice. J Immunol 167:4686–4692

    CAS  PubMed  Google Scholar 

  • Mattsson B, Sorensen JC, Zimmer J, Johansson BB (1997) Neural grafting to experimental neocortical infarcts improves behavioral outcome and reduces thalamic atrophy in rats housed in enriched but not in standard environments. Stroke 28:1225–1231 (discussion 1231–1232)

    CAS  PubMed  Google Scholar 

  • McKay R (1997) Stem cells in the central nervous system. Science 276:66–71

    CAS  PubMed  Google Scholar 

  • Meletis K, Wirta V, Hede SM, Nister M, Lundeberg J, Frisen J (2006) p53 suppresses the self-renewal of adult neural stem cells. Development 133:363–369

    CAS  PubMed  Google Scholar 

  • Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250

    CAS  PubMed  Google Scholar 

  • Modan B, Wagener DK (1992) Some epidemiological aspects of stroke: mortality/morbidity trends, age, sex, race, socioeconomic status. Stroke 23:1230–1236

    CAS  PubMed  Google Scholar 

  • Ninomiya M, Yamashita T, Araki N, Okano H, Sawamoto K (2006) Enhanced neurogenesis in the ischemic striatum following EGF-induced expansion of transit-amplifying cells in the subventricular zone. Neurosci Lett 403:63–67

    CAS  PubMed  Google Scholar 

  • Ohab JJ, Fleming S, Blesch A, Carmichael ST (2006) A neurovascular niche for neurogenesis after stroke. J Neurosci 26:13007–13016

    CAS  PubMed  Google Scholar 

  • Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM (2002) Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 52:802–813

    PubMed  Google Scholar 

  • Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (2001) Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 21:6706–6717

    CAS  PubMed  Google Scholar 

  • Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N et al (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3:687–694

    CAS  PubMed  Google Scholar 

  • Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF (2001) Spontaneous intracerebral hemorrhage. N Engl J Med 344:1450–1460

    CAS  PubMed  Google Scholar 

  • Rafalowska J (2002) Experimental and human ischaemia: is the penumbra present in human ischaemic stroke? Folia Neuropathol 40:211–217

    PubMed  Google Scholar 

  • Ramm P, Couillard-Despres S, Plotz S, Rivera FJ, Krampert M, Lehner B, Kremer W, Bogdahn U, Kalbitzer HR, Aigner L (2008) A NMR biomarker for neural progenitor cells: is it all neurogenesis? Stem Cells

  • Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18:399–404

    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 

  • Reynolds BA, Weiss S (1996) Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 175:1–13

    CAS  PubMed  Google Scholar 

  • Richards LJ, Kilpatrick TJ, Bartlett PF (1992) De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci USA 89:8591–8595

    CAS  PubMed  Google Scholar 

  • Sawamoto K, Wichterle H, Gonzalez-Perez O, Cholfin JA, Yamada M, Spassky N, Murcia NS, Garcia-Verdugo JM, Marin O, Rubenstein JL et al (2006) New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311:629–632

    CAS  PubMed  Google Scholar 

  • Schanzer A, Wachs FP, Wilhelm D, Acker T, Cooper-Kuhn C, Beck H, Winkler J, Aigner L, Plate KH, Kuhn HG (2004) Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Brain Pathol 14:237–248

    PubMed  Google Scholar 

  • Shen LH, Li Y, Chen J, Zhang J, Vanguri P, Borneman J, Chopp M (2006) Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 137:393–399

    CAS  PubMed  Google Scholar 

  • Shim JW, Park CH, Bae YC, Bae JY, Chung S, Chang MY, Koh HC, Lee HS, Hwang SJ, Lee KH et al (2007) Generation of functional dopamine neurons from neural precursor cells isolated from the subventricular zone and white matter of the adult rat brain using Nurr1 overexpression. Stem Cells 25:1252–1262

    CAS  PubMed  Google Scholar 

  • Shingo T, Sorokan ST, Shimazaki T, Weiss S (2001) Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 21:9733–9743

    CAS  PubMed  Google Scholar 

  • Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, Li H (2004) Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110:1847–1854

    CAS  PubMed  Google Scholar 

  • Shyu WC, Lee YJ, Liu DD, Lin SZ, Li H (2006) Homing genes, cell therapy and stroke. Front Biosci 11:899–907

    CAS  PubMed  Google Scholar 

  • Shyu WC, Liu DD, Lin SZ, Li WW, Su CY, Chang YC, Wang HJ, Wang HW, Tsai CH, Li H (2008) Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke. J Clin Invest 118:2482–2495

    CAS  PubMed  Google Scholar 

  • Sorensen JC, Grabowski M, Zimmer J, Johansson BB (1996) Fetal neocortical tissue blocks implanted in brain infarcts of adult rats interconnect with the host brain. Exp Neurol 138:227–235

    CAS  PubMed  Google Scholar 

  • Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Hollt V, Schulz S (2002) A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci 22:5865–5878

    CAS  PubMed  Google Scholar 

  • Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM et al (2004) Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:330–338

    CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    CAS  PubMed  Google Scholar 

  • Tang Y, Yasuhara T, Hara K, Matsukawa N, Maki M, Yu G, Xu L, Hess DC, Borlongan CV (2007) Transplantation of bone marrow-derived stem cells: a promising therapy for stroke. Cell Transplant 16:159–169

    PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    CAS  PubMed  Google Scholar 

  • Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, Ekdahl CT, Kokaia Z, Lindvall O (2006) Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24:739–747

    CAS  PubMed  Google Scholar 

  • Toda H, Takahashi J, Iwakami N, Kimura T, Hoki S, Mozumi-Kitamura K, Ono S, Hashimoto N (2001) Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci Lett 316:9–12

    CAS  PubMed  Google Scholar 

  • Touzani O, Young AR, Derlon JM, Beaudouin V, Marchal G, Rioux P, Mezenge F, Baron JC, MacKenzie ET (1995) Sequential studies of severely hypometabolic tissue volumes after permanent middle cerebral artery occlusion. A positron emission tomographic investigation in anesthetized baboons. Stroke 26:2112–2119

    CAS  PubMed  Google Scholar 

  • Tropepe V, Craig CG, Morshead CM, van der Kooy D (1997) Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci 17:7850–7859

    CAS  PubMed  Google Scholar 

  • Wernig M, Benninger F, Schmandt T, Rade M, Tucker KL, Bussow H, Beck H, Brustle O (2004) Functional integration of embryonic stem cell-derived neurons in vivo. J Neurosci 24:5258–5268

    CAS  PubMed  Google Scholar 

  • Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 105:5856–5861

    CAS  PubMed  Google Scholar 

  • Xiao J, Nan Z, Motooka Y, Low WC (2005) Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev 14:722–733

    CAS  PubMed  Google Scholar 

  • Yamashita T, Ninomiya M, Hernandez Acosta P, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T et al (2006) Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci 26:6627–6636

    CAS  PubMed  Google Scholar 

  • Yan YP, Sailor KA, Vemuganti R, Dempsey RJ (2006) Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation. Eur J Neurosci 24:45–54

    PubMed  Google Scholar 

  • Yan YP, Sailor KA, Lang BT, Park SW, Vemuganti R, Dempsey RJ (2007) Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. J Cereb Blood Flow Metab 27:1213–1224

    CAS  PubMed  Google Scholar 

  • Yoon YS, Wecker A, Heyd L, Park JS, Tkebuchava T, Kusano K, Hanley A, Scadova H, Qin G, Cha DH et al (2005) Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest 115:326–338

    CAS  PubMed  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    CAS  PubMed  Google Scholar 

  • Zhang R, Zhang L, Zhang Z, Wang Y, Lu M, Lapointe M, Chopp M (2001) A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann Neurol 50:602–611

    CAS  PubMed  Google Scholar 

  • Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M, Zhang L, Chopp M (2002) Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 33:2675–2680

    CAS  PubMed  Google Scholar 

  • Zhang ZG, Jiang Q, Zhang R, Zhang L, Wang L, Zhang L, Arniego P, Ho KL, Chopp M (2003) Magnetic resonance imaging and neurosphere therapy of stroke in rat. Ann Neurol 53:259–263

    PubMed  Google Scholar 

  • Zhang R, Zhang Z, Zhang C, Zhang L, Robin A, Wang Y, Lu M, Chopp M (2004) Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat. J Neurosci 24:5810–5815

    CAS  PubMed  Google Scholar 

  • Zhang RL, Zhang Z, Zhang L, Wang Y, Zhang C, Chopp M (2006a) Delayed treatment with sildenafil enhances neurogenesis and improves functional recovery in aged rats after focal cerebral ischemia. J Neurosci Res 83:1213–1219

    CAS  PubMed  Google Scholar 

  • Zhang RL, Zhang ZG, Lu M, Wang Y, Yang JJ, Chopp M (2006b) Reduction of the cell cycle length by decreasing G1 phase and cell cycle reentry expand neuronal progenitor cells in the subventricular zone of adult rat after stroke. J Cereb Blood Flow Metab 26:857–863

    PubMed  Google Scholar 

  • Zhang RL, Zhang ZG, Roberts C, LeTourneau Y, Lu M, Zhang L, Wang Y, Chopp M (2008) Lengthening the G(1) phase of neural progenitor cells is concurrent with an increase of symmetric neuron generating division after stroke. J Cereb Blood Flow Metab 28:602–611

    PubMed  Google Scholar 

  • Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11–20

    PubMed  Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author thanks Dr. Barry Hoffer for helpful discussion and critical comments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu Luo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luo, Y. Cell-based therapy for stroke. J Neural Transm 118, 61–74 (2011). https://doi.org/10.1007/s00702-010-0478-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-010-0478-4

Keywords

Navigation