Abstract
The development of effective strategies for the treatment of stroke is one of the potential applications of stem cell therapy. Various transplantation methods, cell types, and animal models have been examined to investigate the potential benefits of stem cell therapy for stroke, with promising results. Improvements in the methodology of transplantation will lead to improved outcomes in animal models of stroke, which will translate to greater efficacy of stem cell therapies in clinical trials. Recent studies show a growing consensus that intra-arterial delivery of stem cells is well-suited for the treatment of stroke. The goal of intra-arterial delivery is to increase the efficiency of cell engraftment and specific targeting to areas of stroke pathology. However, evidence suggests that not all neural and glial stem cells may have the requisite properties to sufficiently migrate from the blood into the brain parenchyma. Thus, methods to enhance the adhesive and migratory properties of cells via cell engineering, or the enrichment of cell types that endogenously express such molecules, are critical for improving intra-arterial transplantation. Intra-arterial delivery of engineered cells, combined with the use of noninvasive, real-time MRI, will provide a path forward for safe and effective stem cell therapy for stroke.
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References
Adonai N, Nguyen KN, Walsh J, Iyer M, Toyokuni T, Phelps ME, McCarthy T, McCarthy DW, Gambhir SS (2002) Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthioÂsemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci USA 99:3030–3035
Alsop DC (2012) Arterial spin labeling: its time is now. MAGMA 25:75–77
Andres RH, Choi R, Pendharkar AV, Gaeta X, Wang N, Nathan JK, Chua JY, Lee SW, Palmer TD, Steinberg GK et al (2011) The CCR2/CCL2 interaction mediates the transendothelial recruitment of intravascularly delivered neural stem cells to the ischemic brain. Stroke 42:2923–2931
Barnett BP, Arepally A, Karmarkar PV, Qian D, Gilson WD, Walczak P, Howland V, Lawler L, Lauzon C, Stuber M et al (2007) Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med 13:986–991
Berman SC, Galpoththawela C, Gilad AA, Bulte JW, Walczak P (2011) Long-term MR cell tracking of neural stem cells grafted in immunocompetent versus immunodeficient mice reveals distinct differences in contrast between live and dead cells. Magn Reson Med 65:564–574
Bliss TM, Andres RH, Steinberg GK (2010) Optimizing the success of cell transplantation therapy for stroke. Neurobiol Dis 37:275–283
Boncoraglio, GB, Bersano, A, Candelise, L, Reynolds, BA, and Parati, EA (2010) Stem cell transplantation for ischemic stroke. Cochrane Database Syst Rev CD007231
Capetian P, Knoth R, Maciaczyk J, Pantazis G, Ditter M, Bokla L, Landwehrmeyer GB, Volk B, Nikkhah G (2009) Histological findings on fetal striatal grafts in a Huntington’s disease patient early after transplantation. Neuroscience 160:661–675
Correia AS, Anisimov SV, Li JY, Brundin P (2005) Stem cell-based therapy for Parkinson’s disease. Ann Med 37:487–498
Detre JA, Samuels OB, Alsop DC, Gonzalez-At JB, Kasner SE, Raps EC (1999) Noninvasive magnetic resonance imaging evaluation of cerebral blood flow with acetazolamide challenge in patients with cerebrovascular stenosis. J Magn Reson Imaging 10:870–875
Dijkhuizen RM, Nicolay K (2003) Magnetic resonance imaging in experimental models of brain disorders. J Cereb Blood Flow Metab 23:1383–1402
Dirnagl U, Kaplan B, Jacewicz M, Pulsinelli W (1989) Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J Cereb Blood Flow Metab 9:589–596
Engelhardt B (2006) Molecular mechanisms involved in T cell migration across the blood-brain barrier. J Neural Transm 113:477–485
Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI, Laine GA, Cox CS Jr (2009) Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev 18:683–692
Gorelik M, Orukari I, Wang J, Galpoththawela C, Kim H, Levy M, Gilad AA, Bar-Shir A, Kerr DA, Levchenko A et al (2012) Using MRI cell tracking to evaluate targeting of glial precursor cells to inflammatory tissue using the VLA-4 docking receptor. Radiology 265:175–185
Gutierrez-Fernandez M, Rodriguez-Frutos B, Alvarez-Grech J, Vallejo-Cremades MT, Exposito-Alcaide M, Merino J, Roda JM, Diez-Tejedor E (2011) Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats. Neuroscience 175:394–405
Guzman R, De Los Angeles A, Cheshier S, Choi R, Hoang S, Liauw J, Schaar B, Steinberg G (2008) Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model. Stroke 39:1300–1306
Hossmann KA (1994) Viability thresholds and the penumbra of focal ischemia. Ann Neurol 36:557–565
Janowski M, Walczak P, Date I (2010) Intravenous route of cell delivery for treatment of neurological disorders: a meta-analysis of preclinical results. Stem Cells Dev 19:5–16
Justicia C, Martin A, Rojas S, Gironella M, Cervera A, Panes J, Chamorro A, Planas AM (2006) Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice. J Cereb Blood Flow Metab 26:421–432
Karmarkar PV, Kraitchman DL, Izbudak I, Hofmann LV, Amado LC, Fritzges D, Young R, Pittenger M, Bulte JW, Atalar E (2004) MR-trackable intramyocardial injection catheter. Magn Reson Med 51:1163–1172
Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O et al (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 67:1187–1194
Kelly S, Bliss TM, Shah AK, Sun GH, Ma M, Foo WC, Masel J, Yenari MA, Weissman IL, Uchida N et al (2004) Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex. Proc Natl Acad Sci USA 101:11839–11844
Koenig M, Klotz E, Luka B, Venderink DJ, Spittler JF, Heuser L (1998) Perfusion CT of the brain: diagnostic approach for early detection of ischemic stroke. Radiology 209:85–93
Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J, Jannetta P, DeCesare S, Elder EM, McGrogan M et al (2000) Transplantation of cultured human neuronal cells for patients with stroke. Neurology 55:565–569
Kondziolka D, Steinberg GK, Wechsler L, Meltzer CC, Elder E, Gebel J, Decesare S, Jovin T, Zafonte R, Lebowitz J et al (2005) Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 103:38–45
Konstas AA, Goldmakher GV, Lee TY, Lev MH (2009) Theoretic basis and technical implementations of CT perfusion in acute ischemic stroke, part 2: technical implementations. AJNR Am J Neuroradiol 30:885–892
Kraitchman DL, Tatsumi M, Gilson WD, Ishimori T, Kedziorek D, Walczak P, Segars P, Chen HH, Fritzges D, Izbudak I et al (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112:1451–1461
Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N et al (2002) Human marrow stromal cell therapy for stroke in rat – neurotrophins and functional recovery. Neurology 59:514–523
Li L, Jiang Q, Ding G, Zhang L, Zhang ZG, Li Q, Panda S, Lu M, Ewing JR, Chopp M (2010) Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study. J Cereb Blood Flow Metab 30:653–662
Lu D, Li Y, Wang L, Chen J, Mahmood A, Chopp M (2001) Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury. J Neurotrauma 18:813–819
Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Boccaletti R, Testa L, Livigni S, Fagioli F (2006) Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res 28:523–526
Minematsu K, Li L, Sotak CH, Davis MA, Fisher M (1992) Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging in rats. Stroke 23:1304–1310; discussion 1310–1301
Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J et al (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54:403–414
Pendharkar AV, Chua JY, Andres RH, Wang N, Gaeta X, Wang H, De A, Choi R, Chen S, Rutt BK et al (2010) Biodistribution of neural stem cells after intravascular therapy for hypoxic-Âischemia. Stroke 41:2064–2070
Poeschla EM, Wong-Staal F, Looney DJ (1998) Efficient transduction of nondividing human cells by feline immunodeficiency virus lentiviral vectors. Nat Med 4:354–357
Robbins PB, Sheu SM, Goodnough JB, Khavari PA (2001) Impact of laminin 5 beta3 gene versus protein replacement on gene expression patterns in junctional epidermolysis bullosa. Hum Gene Ther 12:1443–1448
Rymer MM, Thrutchley DE (2005) Organizing regional networks to increase acute stroke intervention. Neurol Res 27:S9–S16
Sahni V, Kessler JA (2010) Stem cell therapies for spinal cord injury. Nat Rev Neurol 6:363–372
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
Sotak CH (2002) The role of diffusion tensor imaging in the evaluation of ischemic brain injury – a review. NMR Biomed 15:561–569
Sun PZ, Zhou J, Sun W, Huang J, van Zijl PC (2007) Detection of the ischemic penumbra using pH-weighted MRI. J Cereb Blood Flow Metab. 27:1129–36
Tang Y, Shah K, Messerli SM, Snyder E, Breakefield X, Weissleder R (2003) In vivo tracking of neural progenitor cell migration to glioblastomas. Hum Gene Ther 14:1247–1254
Tran PB, Ren D, Veldhouse TJ, Miller RJ (2004) Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells. J Neurosci Res 76:20–34
Tran-Dinh A, Kubis N, Tomita Y, Karaszewski B, Calando Y, Oudina K, Petite H, Seylaz J, Pinard E (2006) In vivo imaging with cellular resolution of bone marrow cells transplanted into the ischemic brain of a mouse. Neuroimage 31:958–967
Van Tendeloo VF, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN (2001) Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood 98:49–56
Villringer A, Chance B (1997) Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci 20:435–442
Walczak P, Chen N, Hudson JE, Willing AE, Garbuzova-Davis SN, Song S, Sanberg PR, Sanchez-Ramos J, Bickford PC, Zigova T (2004) Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors? J Neurosci Res 76:244–254
Walczak P, Zhang J, Gilad AA, Kedziorek DA, Ruiz-Cabello J, Young RG, Pittenger MF, van Zijl PC, Huang J, Bulte JW (2008) Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke 39:1569–1574
Walczak P, All AH, Rumpal N, Gorelik M, Kim H, Maybhate A, Agrawal G, Campanelli JT, Gilad AA, Kerr DA et al (2011) Human glial-restricted progenitors survive, proliferate, and preserve electrophysiological function in rats with focal inflammatory spinal cord demyelination. Glia 59:499–510
Wintermark M, Flanders AE, Velthuis B, Meuli R, van Leeuwen M, Goldsher D, Pineda C, Serena J, van der Schaaf I, Waaijer A et al (2006) Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute Âhemispheric stroke. Stroke 37:979–985
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Gorelik, M., Walczak, P. (2013). Strategies for Enhanced, MRI-Guided Targeting of Stem Cells to Stroke Lesions. In: Jolkkonen, J., Walczak, P. (eds) Cell-Based Therapies in Stroke. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1175-8_6
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