Neurotrophic Bone Marrow Cellular Nests Prevent Spinal Motoneuron Degeneration in Amyotrophic Lateral Sclerosis Patients: A Pilot Safety Study
The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I tr...
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Published in | Stem cells (Dayton, Ohio) Vol. 30; no. 6; pp. 1277 - 1285 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.06.2012
Oxford University Press |
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Abstract | The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant‐related adverse events. In addition, forced vital capacity (FVC), ALS‐functional rating scale (ALS‐FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant‐related adverse event, but there were 43 nonsevere events. Twenty‐two (51%) resolved in ≤2 weeks and only four were still present at the end of follow‐up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS‐FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post‐transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity. STEM CELLS2012;30:1277–1285 |
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AbstractList | The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity. STEM CELLS2012;30:1277-1285 [PUBLICATION ABSTRACT] The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant‐related adverse events. In addition, forced vital capacity (FVC), ALS‐functional rating scale (ALS‐FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant‐related adverse event, but there were 43 nonsevere events. Twenty‐two (51%) resolved in ≤2 weeks and only four were still present at the end of follow‐up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS‐FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post‐transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity. STEM CELLS2012;30:1277–1285 The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity. Abstract The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity. Disclosure of potential conflicts of interest is found at the end of this article. |
Author | Villaverde, Ramón Sáez, María Martínez-Lage, Juan Francisco Martínez, Salvador Gómez-Espuch, Joaquín Sánchez-Salinas, Andrés Blanquer, Miguel Antúnez, Carmen Ruíz-López, Francisco José Meca-Lallana, José De Mingo, Pedro Izura, Virginia Iniesta, Francisca Carles, Rafael Vivancos, Laura Moraleda, Jose M. García Santos, José María Pérez-Espejo, Miguel Ángel Majado, Maria Juliana López, Javier Hernández, Joaquín Guardiola, Julia De La Rosa, Pedro Jiménez, Judith Bleda, Patricia Del Rio, Silvia Torres |
Author_xml | – sequence: 1 givenname: Miguel surname: Blanquer fullname: Blanquer, Miguel organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 2 givenname: Jose M. surname: Moraleda fullname: Moraleda, Jose M. email: jmoraled@um.es organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 3 givenname: Francisca surname: Iniesta fullname: Iniesta, Francisca organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 4 givenname: Joaquín surname: Gómez-Espuch fullname: Gómez-Espuch, Joaquín organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 5 givenname: José surname: Meca-Lallana fullname: Meca-Lallana, José organization: Neurology,Universidad de Murcia, Murcia, Spain – sequence: 6 givenname: Ramón surname: Villaverde fullname: Villaverde, Ramón organization: Neurology, Universidad de Murcia, Murcia, Spain – sequence: 7 givenname: Miguel Ángel surname: Pérez-Espejo fullname: Pérez-Espejo, Miguel Ángel organization: Neurosurgery,Universidad de Murcia, Murcia, Spain – sequence: 8 givenname: Francisco José surname: Ruíz-López fullname: Ruíz-López, Francisco José organization: Neumology,Universidad de Murcia, Murcia, Spain – sequence: 9 givenname: José María surname: García Santos fullname: García Santos, José María organization: Radiology, Hospital Morales Meseguer, Universidad de Murcia, Murcia, Spain – sequence: 10 givenname: Patricia surname: Bleda fullname: Bleda, Patricia organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 11 givenname: Virginia surname: Izura fullname: Izura, Virginia organization: Neurophysiology,Universidad de Murcia, Murcia, Spain – sequence: 12 givenname: María surname: Sáez fullname: Sáez, María organization: Neurophysiology,Universidad de Murcia, Murcia, Spain – sequence: 13 givenname: Pedro surname: De Mingo fullname: De Mingo, Pedro organization: Neurophysiology,Universidad de Murcia, Murcia, Spain – sequence: 14 givenname: Laura surname: Vivancos fullname: Vivancos, Laura organization: Neuropsychology,Universidad de Murcia, Murcia, Spain – sequence: 15 givenname: Rafael surname: Carles fullname: Carles, Rafael organization: Neuropsychology,Universidad de Murcia, Murcia, Spain – sequence: 16 givenname: Judith surname: Jiménez fullname: Jiménez, Judith organization: Neuropsychology,Universidad de Murcia, Murcia, Spain – sequence: 17 givenname: Joaquín surname: Hernández fullname: Hernández, Joaquín organization: Anesthesiology, Hospital Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain – sequence: 18 givenname: Julia surname: Guardiola fullname: Guardiola, Julia organization: Neumology,Universidad de Murcia, Murcia, Spain – sequence: 19 givenname: Silvia Torres surname: Del Rio fullname: Del Rio, Silvia Torres organization: Radiology, Hospital Morales Meseguer, Universidad de Murcia, Murcia, Spain – sequence: 20 givenname: Carmen surname: Antúnez fullname: Antúnez, Carmen organization: Neurology, Universidad de Murcia, Murcia, Spain – sequence: 21 givenname: Pedro surname: De La Rosa fullname: De La Rosa, Pedro organization: Neurosurgery,Universidad de Murcia, Murcia, Spain – sequence: 22 givenname: Maria Juliana surname: Majado fullname: Majado, Maria Juliana organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 23 givenname: Andrés surname: Sánchez-Salinas fullname: Sánchez-Salinas, Andrés organization: Hematopoietic Progenitors Transplant and Cell Therapy Unit,Universidad de Murcia, Murcia, Spain – sequence: 24 givenname: Javier surname: López fullname: López, Javier organization: Statistical Analysis, Fundación para la Formación e Investigación Sanitarias de la Región de Murcia, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain – sequence: 25 givenname: Juan Francisco surname: Martínez-Lage fullname: Martínez-Lage, Juan Francisco organization: Neurosurgery,Universidad de Murcia, Murcia, Spain – sequence: 26 givenname: Salvador surname: Martínez fullname: Martínez, Salvador organization: Instituto de Neurociencias, UMH-CSIC, Alicante, Spain |
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Notes | GVA Prometeo Grant - No. 2009/028 Disclosure of potential conflicts of interest is found at the end of this article. istex:7B3018C338E85731223FE185571BC5E2ED40DA45 First published online in STEM CELLSEXPRESS March 13, 2012. Advanced Therapies and Transplant General Direction (Health Ministry, Spain) - No. TRA-137 Carlos III Institute - No. FIS EC07/90762 Rotary Club Elche-Illice and by the Fundación Diógenes ArticleID:STEM1080 ISCIII Spanish Cell Therapy Network - No. Tercel; RD06/0010/0023; No. DIGESIC-MEC BFU2008-00588; No. Ingenio 2010 MEC-CONSOLIDER CSD2007-00023 Author contributions: M.B.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; J.M.J. and S.M.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript; F.I.: administrative support, collection and/or assembly of data, and data analysis and interpretation; J.G.E., J.M., and R.V.: conception and design, provision of patients, collection and/or assembly of data, and data analysis and interpretation; M.Á.P.E.: conception and design and provision of patients; F.J.R.L., J.M.G.S., V.I., and L.V.: conception and design, collection and assembly of data, and data analysis and interpretation; M.S., P.d.M., R.C., and J.J.: conception and design, collection of data, and data analysis and interpretation; C.A.: administrative support and provision of study material; M.J.M. and A.S.S.: provision of study material and collection of data; J.L.: assembly of data, and data analysis and interpretation; J.F.M.-L.: conception and design. ark:/67375/WNG-W32XL57F-4 First published online in S Author contributions: M.B.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; J.M.J. and S.M.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript; F.I.: administrative support, collection and/or assembly of data, and data analysis and interpretation; J.G.E., J.M., and R.V.: conception and design, provision of patients, collection and/or assembly of data, and data analysis and interpretation; M.Á.P.E.: conception and design and provision of patients; F.J.R.L., J.M.G.S., V.I., and L.V.: conception and design, collection and assembly of data, and data analysis and interpretation; M.S., P.d.M., R.C., and J.J.: conception and design, collection of data, and data analysis and interpretation; C.A.: administrative support and provision of study material; M.J.M. and A.S.S.: provision of study material and collection of data; J.L.: assembly of data, and data analysis and interpretation; J.F.M.‐L.: conception and design. C EXPRESS March 13, 2012. Telephone: +34‐968369532; Fax: +34‐968369088 TEM ELLS ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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PublicationPlace | Hoboken |
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PublicationTitle | Stem cells (Dayton, Ohio) |
PublicationTitleAlternate | STEM CELLS |
PublicationYear | 2012 |
Publisher | Wiley Subscription Services, Inc., A Wiley Company Oxford University Press |
Publisher_xml | – name: Wiley Subscription Services, Inc., A Wiley Company – name: Oxford University Press |
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References_xml | – volume: 11 start-page: 18 year: 2009 end-page: 25 article-title: Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow‐derived hematopoietic stem cell transplantation: A 1‐year follow‐up publication-title: Cytotherapy – volume: 13 start-page: 10 year: 2003 end-page: 22 article-title: Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000 publication-title: Brain Pathol – volume: 4 start-page: 3 year: 2009 end-page: 25 article-title: Amyotrophic lateral sclerosis publication-title: Orphanet J Rare Dis – volume: 11 start-page: 26 year: 2009 end-page: 34 article-title: Stem‐cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients publication-title: Cytotherapy – volume: 314 start-page: 130 year: 2006 end-page: 133 article-title: Ubiquitinated TDP‐43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis publication-title: Science – volume: 26 start-page: 408 year: 2007 end-page: 418 article-title: Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration publication-title: Neurobiol Dis – volume: 85 start-page: 717 year: 2005 end-page: 756 article-title: Respiratory action of the intercostal muscles publication-title: Physiol Rev – year: 2007 – volume: 31 start-page: 192 year: 2008 end-page: 198 article-title: Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis publication-title: Trends Neurosci – volume: 32 start-page: 31 issue: suppl A year: 2010 end-page: 37 article-title: [Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: Technical aspects and preliminary results from a clinical trial] publication-title: Methods Find Exp Clin Pharmacol – volume: 5 start-page: 577 year: 2009 end-page: 595 article-title: Current and emerging treatments for amyotrophic lateral sclerosis publication-title: Neuropsychiatr Dis Treat – volume: 191 start-page: 255 year: 2010 end-page: 257 article-title: A surgical technique of spinal cord cell transplantation in amyotrophic lateral sclerosis publication-title: J Neurosci Methods – volume: 9 start-page: 995 year: 2010 end-page: 1007 article-title: TDP‐43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia publication-title: Lancet Neurol – volume: 54 start-page: 812 year: 1995 end-page: 825 article-title: The mouse mutation muscle deficient (mdf) is characterized by a progressive motoneuron disease publication-title: J Neuropathol Exp Neurol – volume: 6 start-page: CD005225 year: 2010 article-title: Creatine for amyotrophic lateral sclerosis/motor neuron disease publication-title: Cochrane Database Syst Rev – volume: 81 start-page: 385 year: 2010 end-page: 390 article-title: Incidence of amyotrophic lateral sclerosis in Europe publication-title: J Neurol Neurosurg Psychiatry – volume: 50 start-page: 1131 year: 1995 end-page: 1135 article-title: Measurement of respiratory muscle strength publication-title: Thorax – volume: 1 start-page: 293 year: 2000 end-page: 299 article-title: El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis publication-title: Amyotroph Lateral Scler Other Motor Neuron Disord – volume: 223 start-page: 229 year: 2010 end-page: 237 article-title: Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial publication-title: Exp Neurol – volume: 377 start-page: 942 year: 2011 end-page: 955 article-title: Amyotrophic lateral sclerosis publication-title: Lancet – volume: 5 start-page: 516 year: 2008 end-page: 527 article-title: ALS drug development: Reflections from the past and a way forward publication-title: Neurotherapeutics – volume: 119 start-page: 1705 year: 2008 end-page: 1719 article-title: Recommendations for the clinical use of somatosensory‐evoked potentials publication-title: Clin Neurophysiol – volume: 1 start-page: CD001447 year: 2007 article-title: Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) publication-title: Cochrane Database Syst Rev – year: 2011 article-title: Comparative effects between bone marrow and mesenchymal stem cell transplantation in GDNF expression and motor function recovery in a motorneuron degenerative mouse model publication-title: Stem Cell Rev – volume: 17 start-page: 74 year: 2006 end-page: 77 article-title: Adult stem cell therapy: Dream or reality? 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Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors publication-title: J Neurol Sci doi: 10.1016/0022-510X(94)90191-0 contributor: fullname: Brooks – volume: 119 start-page: 1705 year: 2008 ident: 2022011204154011200_bib25 article-title: Recommendations for the clinical use of somatosensory-evoked potentials publication-title: Clin Neurophysiol doi: 10.1016/j.clinph.2008.03.016 contributor: fullname: Cruccu – volume: 6 start-page: CD005225 year: 2010 ident: 2022011204154011200_bib7 article-title: Creatine for amyotrophic lateral sclerosis/motor neuron disease publication-title: Cochrane Database Syst Rev contributor: fullname: Pastula – volume: 5 start-page: 516 year: 2008 ident: 2022011204154011200_bib8 article-title: ALS drug development: Reflections from the past and a way forward publication-title: Neurotherapeutics doi: 10.1016/j.nurt.2008.08.002 contributor: fullname: Aggarwal – volume: 81 start-page: 385 year: 2010 ident: 2022011204154011200_bib1 article-title: Incidence of amyotrophic lateral sclerosis in Europe publication-title: J Neurol Neurosurg Psychiatry doi: 10.1136/jnnp.2009.183525 contributor: fullname: Logroscino – volume: 141 start-page: 781 year: 2004 ident: 2022011204154011200_bib18 article-title: Better reporting of harms in randomized trials: An extension of the CONSORT statement publication-title: Ann Intern Med doi: 10.7326/0003-4819-141-10-200411160-00009 contributor: fullname: Ioannidis – volume: 13 start-page: 176 year: 2003 ident: 2022011204154011200_bib20 article-title: CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment publication-title: Semin Radiat Oncol doi: 10.1016/S1053-4296(03)00031-6 contributor: fullname: Trotti – volume: 191 start-page: 255 year: 2010 ident: 2022011204154011200_bib23 article-title: A surgical technique of spinal cord cell transplantation in amyotrophic lateral sclerosis publication-title: J Neurosci Methods doi: 10.1016/j.jneumeth.2010.06.014 contributor: fullname: Blanquer – volume-title: The AASM Manual for the Scoring of Sleep and Associated Events-Rules, Terminology and Technical Specifications year: 2007 ident: 2022011204154011200_bib26 contributor: fullname: Iber – volume: 223 start-page: 229 year: 2010 ident: 2022011204154011200_bib11 article-title: Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial publication-title: Exp Neurol doi: 10.1016/j.expneurol.2009.08.007 contributor: fullname: Mazzini – volume: 61 start-page: 427 year: 2007 ident: 2022011204154011200_bib27 article-title: Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations publication-title: Ann Neurol doi: 10.1002/ana.21147 contributor: fullname: Mackenzie – volume: 26 start-page: 408 year: 2007 ident: 2022011204154011200_bib16 article-title: Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration publication-title: Neurobiol Dis doi: 10.1016/j.nbd.2007.01.008 contributor: fullname: Cabanes – volume: 377 start-page: 942 year: 2011 ident: 2022011204154011200_bib3 article-title: Amyotrophic lateral sclerosis publication-title: Lancet doi: 10.1016/S0140-6736(10)61156-7 contributor: fullname: Kiernan – volume: 32 start-page: 31 issue: suppl A year: 2010 ident: 2022011204154011200_bib31 article-title: [Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: Technical aspects and preliminary results from a clinical trial] publication-title: Methods Find Exp Clin Pharmacol contributor: fullname: Blanquer – volume: 314 start-page: 130 year: 2006 ident: 2022011204154011200_bib6 article-title: Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis publication-title: Science doi: 10.1126/science.1134108 contributor: fullname: Neumann – volume: 4 start-page: 3 year: 2009 ident: 2022011204154011200_bib2 article-title: Amyotrophic lateral sclerosis publication-title: Orphanet J Rare Dis doi: 10.1186/1750-1172-4-3 contributor: fullname: Wijesekera – volume: 85 start-page: 717 year: 2005 ident: 2022011204154011200_bib19 article-title: Respiratory action of the intercostal muscles publication-title: Physiol Rev doi: 10.1152/physrev.00007.2004 contributor: fullname: De Troyer – volume: 50 start-page: 1131 year: 1995 ident: 2022011204154011200_bib24 article-title: Measurement of respiratory muscle strength publication-title: Thorax doi: 10.1136/thx.50.11.1131 contributor: fullname: Polkey |
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Snippet | The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for... Abstract The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to... |
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SubjectTerms | Adult Adult stem cells Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - pathology Amyotrophic Lateral Sclerosis - surgery Bone marrow Bone Marrow Cells - pathology Bone Marrow Transplantation - methods Clinical trials Female Humans Male Middle Aged Motor Neurons - pathology Nerve Degeneration - pathology Pilot Projects Somatic cell therapy Spinal Cord - pathology Spinal Cord - surgery Stem cell transplantation |
Title | Neurotrophic Bone Marrow Cellular Nests Prevent Spinal Motoneuron Degeneration in Amyotrophic Lateral Sclerosis Patients: A Pilot Safety Study |
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