Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis

Stem Cells Translational Medicine

Volumn 4, Issue 6, 2015, Pages 590-597

  Oh, Ki Wook ^a,b   Moon, Chanil ^b   Kim, Hyun Young ^a   Oh, Sung Il ^b,c   Park, Jinseok ^a,b   Lee, Jun Ho ^d   Chang, In Young ^d   Kim, Kyung Suk ^d   Kim, Seung Hyun ^a,b  

^a Hospital of Korean Medicine   (South Korea)

^b Hanyang University College of Medicine   (South Korea)

^c Inje University College of Medicine   (South Korea)

^d Division of Dg and Ai Business   (South Korea)

Author keywords

Amyotrophic lateral sclerosis; Clinical trials; Intrathecal; Mesenchymal stromal cells

Indexed keywords

5' NUCLEOTIDASE; BETA1 INTEGRIN; BONE MARROW DERIVED MESENCHYMAL STEM CELL EXTRACT; CD34 ANTIGEN; CD45 ANTIGEN; CELL EXTRACT; ENDOGLIN; HERMES ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 6; MONOCYTE CHEMOTACTIC PROTEIN 1; RILUZOLE; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TRANSFORMING GROWTH FACTOR BETA3; UNCLASSIFIED DRUG;

ADULT; AGED; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; BONE MARROW CELL; BONE MARROW DERIVED MESENCHYMAL STEM CELL; CEREBROSPINAL FLUID; CLINICAL ARTICLE; FEMALE; FOLLOW UP; FORCED VITAL CAPACITY; HUMAN; MALE; MYOTROPHIC LATERAL SCLEROSIS; NERVE INJURY; NONINVASIVE VENTILATION; OUTCOME ASSESSMENT; PATIENT SAFETY; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; PHASE 1 CLINICAL TRIAL; PROTEIN EXPRESSION; SCORING SYSTEM; TRACHEOSTOMY; AUTOGRAFT; CLINICAL TRIAL; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMA CELL; MIDDLE AGED; MULTICENTER STUDY; PATHOPHYSIOLOGY;

ADULT; AGED; AMYOTROPHIC LATERAL SCLEROSIS; AUTOGRAFTS; BONE MARROW CELLS; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; MIDDLE AGED;

EID: 84930536046     PISSN: 21576564     EISSN: 21576580     Source Type: Journal    
DOI: 10.5966/sctm.2014-0212     Document Type: Article

References (40)

1. Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med 2001;344: 1688–1700.
2. Mitchell JD, Borasio GD. Amyotrophic lateral sclerosis. Lancet 2007;369:2031–2041.
3. Mazzini L, Mareschi K, Ferrero I et al. Mes-enchymal stromal cell transplantation in amyo-trophic lateral sclerosis: A long-term safety study. Cytotherapy 2012;14:56–60.
4. 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.
5. Janson CG, Ramesh TM, During MJ et al. Hu-man intrathecal transplantation of peripheral blood stem cells inamyotrophic lateral sclerosis. J Hematother Stem Cell Res 2001;10:913–915.
6. Martínez HR, Molina-Lopez JF, González-Garza MT et al. Stem cell transplantation in amyotrophic lateral sclerosis patients: Methodological approach, safety, and feasibility. Cell Transplant 2012;21:1899–1907.
7. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98:1076–1084.
8. Koh SH, Noh MY, Cho GW et al. Erythropoi-etin increases the motility of human bone marrow-multipotent stromal cells (hBM-MSCs) and enhances the production of neurotrophic factors from hBM-MSCs. Stem Cells Dev 2009; 18:411–421.
9. 9 Salem HK, Thiemermann C. Mesenchy-mal stromal cells: Current understanding and clinical status. Stem Cells 2010;28: 585–596.
10. English K, Mahon BP. Allogeneic mesen-chymal stem cells: Agents of immune modulation. J Cell Biochem 2011;112:1963–1968.
11. Gebler A, Zabel O, Seliger B. Theimmuno-modulatory capacity of mesenchymal stem cells. Trends Mol Med 2012;18:128–134.
12. Keating A. Mesenchymal stromal cells: New directions. Cell Stem Cell 2012;10:709–716.
13. Kim H, Kim HY, Choi MR et al. Dose-dependent efficacy of ALS-human mesenchy-mal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice. Neurosci Lett 2010;468:190–194.
14. Zhang C, Zhou C, Teng JJ et al. Multiple administrations of human marrow stromal cells through cerebrospinal fluid prolong survival in a transgenic mouse model of amyotro-phic lateral sclerosis. Cytotherapy 2009;11: 299–306.
15. Harris VK, Yan QJ, Vyshkina T et al. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci 2012;313: 167–177.
16. Karussis D, Karageorgiou C, Vaknin-Dembinsky A et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 2010;67:1187–1194.
17. Prabhakar S, Marwaha N, Lal V et al. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: A pilot study. Neurol India 2012;60:465–469.
18. Kim HY, Kim H, Oh KW et al. Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: An investigator-initiated trial and in vivo study. Stem Cells 2014;32:2724–2731.
19. Kim HY, Paek J, Park HK et al. Efficacy and safety of autologous bone marrow-derived mesenchymal stem cell treatment in patients with amyotrophic lateral sclerosis. J Korean Neurol Assoc 2009;27:163–169.
20. Brooks BR, Miller RG, Swash M et al. El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyo-troph Lateral Scler Other Motor Neuron Disord 2000;1:293–299.
21. Ioannidis JPA, Evans SJW, Gøtzsche PC et al. Better reporting of harms in randomized trials:Anextension of the CONSORT statement. Ann Intern Med 2004;141:781–788.
22. Trotti A, Colevas AD, Setser A et al. CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003;13: 176–181.
23. Berry JD, Cudkowicz ME. New considerations in the design of clinical trials for amyotrophic lateral sclerosis. Clin Investig (Lond) 2011;1:1375–1389.
24. Noh MY, Cho KA, Kim H et al. Erythropoi-etin modulates the immune-inflammatory response of a SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS). Neurosci Lett 2014;574:53–58.
25. Beers DR, Henkel JS, Zhao W et al. Endogenous regulatory T lymphocytes ameliorate amyo-trophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 2011;134:1293–1314.
26. Henkel JS, Beers DR, Wen S et al. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med 2013;5:64–79.
27. Kwon MS, Noh MY, Oh KW et al. The immu-nomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells inALS patients. J Neurochem 2014 [Epub aheadof print].
28. Trounson A, Thakar RG, Lomax G et al. Clinical trials for stem cell therapies. BMC Med 2011;9:52.
29. Giordano A, Galderisi U, Marino IR. From the laboratory bench to the patient’s bedside: An update on clinical trials with mes-enchymal stem cells. J Cell Physiol 2007;211: 27–35.
30. Le Blanc K, Pittenger M. Mesenchymal stem cells: Progress toward promise. Cytother-apy 2005;7:36–45.
31. Mazzini L, Ferrero I, Luparello V et al. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp Neurol 2010;223:229–237.
32. Martinez HR, Gonzalez-Garza MT, Moreno-Cuevas JE et al. Stem-cell transplantation into the frontal motor cortex in amyo-trophic lateral sclerosis patients. Cytotherapy 2009;11:26–34.
33. Appel SH, Engelhardt JI, Henkel JS et al. Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology 2008;71:1326–1334.
34. Cashman N, Tan L-Y, Krieger C et al. Pilot study of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells in amyotrophic lateral sclerosis (ALS). Muscle Nerve 2008;37:620–625.
35. Rice CM, Mallam EA, Whone AL et al. Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis. Clin Pharmacol Ther 2010;87: 679–685.
36. Chen L, Chen D, Xi H et al. Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: Benefits from multiple transplantations. Cell Transplant 2012;21(suppl 1):S65–S77.
37. Morita E, Watanabe Y, Ishimoto M et al. A novelcell transplantation protocol and its appli-cationtoanALS mousemodel. ExpNeurol 2008; 213:431–438.
38. Pinto S, Swash M, de Carvalho M. Does surgery accelerate progression of amyotrophic lateral sclerosis? J Neurol Neurosurg Psychiatry 2014;85:643–646.
39. Toma C, Wagner WR, Bowry S et al. Fate of culture-expanded mesenchymal stem cells in the microvasculature: In vivo observations of cell kinetics. Circ Res 2009; 104:398–402.
40. Lee RH, Pulin AA, Seo MJ et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009;5:54–63.