Autocrine Production of IGF‐I Increases Stem Cell‐Mediated Neuroprotection
dc.contributor.author | Lunn, J. Simon | en_US |
dc.contributor.author | Sakowski, Stacey A. | en_US |
dc.contributor.author | McGinley, Lisa M. | en_US |
dc.contributor.author | Pacut, Crystal | en_US |
dc.contributor.author | Hazel, Thomas G. | en_US |
dc.contributor.author | Johe, Karl | en_US |
dc.contributor.author | Feldman, Eva L. | en_US |
dc.date.accessioned | 2015-05-04T20:36:25Z | |
dc.date.available | 2016-07-05T17:27:59Z | en |
dc.date.issued | 2015-05 | en_US |
dc.identifier.citation | Lunn, J. Simon; Sakowski, Stacey A.; McGinley, Lisa M.; Pacut, Crystal; Hazel, Thomas G.; Johe, Karl; Feldman, Eva L. (2015). "Autocrine Production of IGF‐I Increases Stem Cell‐Mediated Neuroprotection." STEM CELLS 33(5): 1480-1489. | en_US |
dc.identifier.issn | 1066-5099 | en_US |
dc.identifier.issn | 1549-4918 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/111155 | |
dc.description.abstract | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression in G93A‐SOD1 ALS rats. Recently, we completed a phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation in ALS patients which demonstrated our approach was safe and feasible, supporting the phase II trial currently in progress. In parallel, efforts focused on understanding the mechanisms underlying the preclinical benefit of HSSCs in vitro and in animal models of ALS led us to investigate how insulin‐like growth factor‐I (IGF‐I) production contributes to cellular therapy neuroprotection. IGF‐I is a potent growth factor with proven efficacy in preclinical ALS studies, and we contend that autocrine IGF‐I production may enhance the salutary effects of HSSCs. By comparing the biological properties of HSSCs to HSSCs expressing sixfold higher levels of IGF‐I, we demonstrate that IGF‐I production augments the production of glial‐derived neurotrophic factor and accelerates neurite outgrowth without adversely affecting HSSC proliferation or terminal differentiation. Furthermore, we demonstrate that increased IGF‐I induces more potent MN protection from excitotoxicity via both indirect and direct mechanisms, as demonstrated using hanging inserts with primary MNs or by culturing with organotypic spinal cord slices, respectively. These findings support our theory that combining autocrine growth factor production with HSSC transplantation may offer a novel means to achieve additive neuroprotection in ALS. Stem Cells 2015;33:1480–1489 | en_US |
dc.publisher | Wiley Periodicals, Inc. | en_US |
dc.subject.other | Neuroprotection | en_US |
dc.subject.other | Key Words. Insulin‐like growth factor‐I | en_US |
dc.subject.other | Growth factor | en_US |
dc.subject.other | Human spinal stem cell | en_US |
dc.subject.other | Amyotrophic lateral sclerosis | en_US |
dc.subject.other | Cellular therapy | en_US |
dc.subject.other | Stem cell | en_US |
dc.title | Autocrine Production of IGF‐I Increases Stem Cell‐Mediated Neuroprotection | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/111155/1/stem1933.pdf | |
dc.identifier.doi | 10.1002/stem.1933 | en_US |
dc.identifier.source | STEM CELLS | en_US |
dc.identifier.citedreference | Mitchell JD, Wokke JH, Borasio GD. Recombinant human insulin‐like growth factor I (rhIGF‐I) for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database SystRev 2002: CD002064. | en_US |
dc.identifier.citedreference | Sorenson EJ, Windbank AJ, Mandrekar JN et al. Subcutaneous IGF‐1 is not beneficial in 2‐year ALS trial. Neurology 2008; 71: 1770 – 1775. | en_US |
dc.identifier.citedreference | Johe KK, Hazel TG, Muller T et al. Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev 1996; 10: 3129 – 3140. | en_US |
dc.identifier.citedreference | Cizkova D, Kakinohana O, Kucharova K et al. Functional recovery in rats with ischemic paraplegia after spinal grafting of human spinal stem cells. Neuroscience 2007; 147: 546 – 560. | en_US |
dc.identifier.citedreference | Lunn JS, Pacut C, Backus C et al. The pleotrophic effects of insulin‐like growth factor‐I on human spinal cord neural progenitor cells. Stem Cells Dev 2010; 19: 1983 – 1993. | en_US |
dc.identifier.citedreference | Vincent AM, Feldman EL, Song DK et al. Adeno‐associated viral‐mediated insulin‐like growth factor delivery protects motor neurons in vitro. Neuromol Med 2004; 6: 79 – 86. | en_US |
dc.identifier.citedreference | Kim B, Leventhal PS, Saltiel AR et al. Insulin‐like growth factor‐I‐mediated neurite outgrowth in vitro requires MAP kinase activation. J Biol Chem 1997; 272: 21268 – 21273. | en_US |
dc.identifier.citedreference | Vincent AM, Mobley BC, Hiller A et al. IGF‐I prevents glutamate‐induced motor neuron programmed cell death. Neurobiol Dis 2004; 16: 407 – 416. | en_US |
dc.identifier.citedreference | Maragakis NJ, Rao MS, Llado J et al. Glial restricted precursors protect against chronic glutamate neurotoxicity of motor neurons in vitro. Glia 2005; 50: 145 – 159. | en_US |
dc.identifier.citedreference | Supeno NE, Pati S, Hadi RA et al. IGF‐1 acts as controlling switch for long‐term proliferation and maintenance of EGF/FGF‐responsive striatal neural stem cells. Int J Med Sci 2013; 10: 522 – 531. | en_US |
dc.identifier.citedreference | Maucksch C, McGregor AL, Yang M et al. IGF‐I redirects doublecortin‐positive cell migration in the normal adult rat brain. Neuroscience 2013; 241: 106 – 115. | en_US |
dc.identifier.citedreference | Borasio GD, Robberecht W, Leigh PN et al. A placebo‐controlled trial of insulin‐like growth factor‐I in amyotrophic lateral sclerosis. European ALS/IGF‐I Study Group. Neurology 1998; 51: 583 – 586. | en_US |
dc.identifier.citedreference | Lai EC, Felice KJ, Festoff BW et al. Effect of recombinant human insulin‐like growth factor‐I on progression of ALS. A placebo‐controlled study. The North America ALS/IGF‐I Study Group. Neurology 1997; 49: 1621 – 1630. | en_US |
dc.identifier.citedreference | Kouroupi G, Lavdas AA, Gaitanou M et al. Lentivirus‐mediated expression of insulin‐like growth factor‐I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons. J Neurochem 2010; 115: 460 – 474. | en_US |
dc.identifier.citedreference | Floyd S, Favre C, Lasorsa FM et al. The insulin‐like growth factor‐I‐mTOR signaling pathway induces the mitochondrial pyrimidine nucleotide carrier to promote cell growth. Mol Biol Cell 2007; 18: 3545 – 3555. | en_US |
dc.identifier.citedreference | Kalluri HS, Vemuganti R, Dempsey RJ. Mechanism of insulin‐like growth factor I‐mediated proliferation of adult neural progenitor cells: Role of Akt. Eur J Neurosci 2007; 25: 1041 – 1048. | en_US |
dc.identifier.citedreference | LeRoith D, Roberts CT, Jr. The insulin‐like growth factor system and cancer. Cancer Lett 2003; 195: 127 – 137. | en_US |
dc.identifier.citedreference | O'Donnell SL, Frederick TJ, Krady JK et al. IGF‐I and microglia/macrophage proliferation in the ischemic mouse brain. Glia 2002; 39: 85 – 97. | en_US |
dc.identifier.citedreference | Raore B, Federici T, Taub J et al. Cervical multilevel intraspinal stem cell therapy: Assessment of surgical risks in Gottingen minipigs. Spine 2011; 36: E164 – 171. | en_US |
dc.identifier.citedreference | Hefferan M, Johe K, Hazel T et al. Optimization of immunosuppressive therapy for spinal grafting of human spinal stem cells in a rat model of ALS. Cell Transplant 2011; 20: 1153 – 1161. | en_US |
dc.identifier.citedreference | Usvald D, Vodicka P, Hlucilova J et al. Analysis of dosing regimen and reproducibility of intraspinal grafting of human spinal stem cells in immunosuppressed minipigs. Cell Transplant 2010; 19: 1103 – 1122. | en_US |
dc.identifier.citedreference | Rizvanov AA, Guseva DS, Salafutdinov II et al. Genetically modified human umbilical cord blood cells expressing vascular endothelial growth factor and fibroblast growth factor 2 differentiate into glial cells after transplantation into amyotrophic lateral sclerosis transgenic mice. Exp Biol Med (Maywood) 2011; 236: 91 – 98. | en_US |
dc.identifier.citedreference | Hossaini M, Sarac C, Jongen JL et al. Spinal glycinergic and GABAergic neurons expressing C‐fos after capsaicin stimulation are increased in rats with contralateral neuropathic pain. Neuroscience 2011; 196: 265 – 275. | en_US |
dc.identifier.citedreference | Knippenberg S, Thau N, Dengler R et al. Intracerebroventricular injection of encapsulated human mesenchymal cells producing glucagon‐like peptide 1 prolongs survival in a mouse model of ALS. PLoS One 2012; 7: e36857. | en_US |
dc.identifier.citedreference | Krakora D, Mulcrone P, Meyer M et al. Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model. Mol Ther 2013; 21: 1602 – 1610. | en_US |
dc.identifier.citedreference | Suzuki M, McHugh J, Tork C et al. Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Mol Ther 2008; 16: 2002 – 2010. | en_US |
dc.identifier.citedreference | Suzuki M, McHugh J, Tork C et al. GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS One 2007; 2: e689. | en_US |
dc.identifier.citedreference | Zinman L, Cudkowicz M. Emerging targets and treatments in amyotrophic lateral sclerosis. Lancet Neurol 2011; 10: 481 – 490. | en_US |
dc.identifier.citedreference | Ilieva H, Polymenidou M, Cleveland DW. Non‐cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 2009; 187: 761 – 772. | en_US |
dc.identifier.citedreference | Just N, Moreau C, Lassalle P et al. High erythropoietin and low vascular endothelial growth factor levels in cerebrospinal fluid from hypoxemic ALS patients suggest an abnormal response to hypoxia. Neuromuscul Disord 2007; 17: 169 – 173. | en_US |
dc.identifier.citedreference | Bilic E, Bilic E, Rudan I et al. Comparison of the growth hormone, IGF‐1 and insulin in cerebrospinal fluid and serum between patients with motor neuron disease and healthy controls. Eur J Neurol 2006; 13: 1340 – 1345. | en_US |
dc.identifier.citedreference | Devos D, Moreau C, Lassalle P et al. Low levels of the vascular endothelial growth factor in CSF from early ALS patients. Neurology. 2004; 62: 2127 – 2129. | en_US |
dc.identifier.citedreference | Lunn JS, Sakowski SA, Hur J et al. Stem cell technology for neurodegenerative diseases. Ann Neurol 2011; 70: 353 – 361. | en_US |
dc.identifier.citedreference | Lunn JS, Sakowski SA, Federici T et al. Stem cell technology for the study and treatment of motor neuron diseases. Regen Med 2011; 6: 201 – 213. | en_US |
dc.identifier.citedreference | Boulis NM, Federici T, Glass JD et al. Translational stem cell therapy for amyotrophic lateral sclerosis. Nat Rev Neurol 2011; 8: 172 – 176. | en_US |
dc.identifier.citedreference | Glass JD, Boulis NM, Johe K et al. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: Results of a phase I trial in 12 patients. Stem Cells 2012; 30: 1144 – 1151. | en_US |
dc.identifier.citedreference | Riley J, Federici T, Polak M et al. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: A phase I safety trial, technical note, and lumbar safety outcomes. Neurosurgery 2012; 71: 405 – 416. | en_US |
dc.identifier.citedreference | Feldman EL, Boulis NM, Hur J et al. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: Phase 1 trial outcomes. Ann Neurol 2014; 75: 363 – 373. | en_US |
dc.identifier.citedreference | Lunn JS, Sakowski SA, Feldman EL. Stem cell therapies for amyotrophic lateral sclerosis: Recent advances and prospects for the future. Stem Cells 2014; 32: 1099 – 1109. | en_US |
dc.identifier.citedreference | Riley J, Glass J, Feldman EL et al. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: A phase I trial, cervical microinjection, and final surgical safety outcomes. Neurosurgery 2014; 74: 77 – 87. | en_US |
dc.identifier.citedreference | Hefferan MP, Galik J, Kakinohana O et al. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation. PLoS One 2012; 7: e42614. | en_US |
dc.identifier.citedreference | Xu L, Ryugo DK, Pongstaporn T et al. Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: Differentiation and structural integration into the segmental motor circuitry. J Comp Neurol 2009; 514: 297 – 309. | en_US |
dc.identifier.citedreference | Xu L, Shen P, Hazel T et al. Dual transplantation of human neural stem cells into cervical and lumbar cord ameliorates motor neuron disease in SOD1 transgenic rats. Neurosci Lett 2011; 494: 222 – 226. | en_US |
dc.identifier.citedreference | Xu L, Yan J, Chen D et al. Human neural stem cell grafts ameliorate motor neuron disease in SOD‐1 transgenic rats. Transplantation 2006; 82: 865 – 875. | en_US |
dc.identifier.citedreference | Yan J, Xu L, Welsh AM et al. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord. PLoS Med 2007; 4: e39. | en_US |
dc.identifier.citedreference | Sakowski SA, Schuyler AD, Feldman EL. Insulin‐like growth factor‐I for the treatment of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2009; 10: 63 – 73. | en_US |
dc.identifier.citedreference | Franz CK, Federici T, Yang J et al. Intraspinal cord delivery of IGF‐I mediated by adeno‐associated virus 2 is neuroprotective in a rat model of familial ALS. Neurobiol Dis 2009; 33: 473 – 481. | en_US |
dc.identifier.citedreference | Dodge JC, Haidet AM, Yang W et al. Delivery of AAV‐IGF‐1 to the CNS extends survival in ALS mice through modification of aberrant glial cell activity. Mol Ther 2008; 16: 1056 – 1064. | en_US |
dc.identifier.citedreference | Dodge JC, Treleaven CM, Fidler JA et al. AAV4‐mediated expression of IGF‐1 and VEGF within cellular components of the ventricular system improves survival outcome in familial ALS mice. Mol Ther 2010; 18: 2075 – 2084. | en_US |
dc.identifier.citedreference | Kaspar BK, Llado J, Sherkat N et al. Retrograde viral delivery of IGF‐1 prolongs survival in a mouse ALS model. Science 2003; 301: 839 – 842. | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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