근위축성측삭경화증 환자에서 자가 골수유래 중간엽줄기세포치료의 유효성 및 안전성
Efficacy and Safety of Autologous Bone Marrow-derived Mesenchymal Stem Cell Treatment in Patients With Amyotrophic Lateral Sclerosis
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background: This study was performed to investigate the efficacy and safety of intrathecal autologous bone marrowderived mesenchymal stem cells (MSCs) treatment for patients with ALS. Methods: After a lead-in period for 3 months, 22 patients were treated with MSCs twice at an interval of 1 month. After initial MSCs injection, all patients were followed up for 3 months and their disease course, clinical characteristics were assessed. Disease status of patients were analyzed with ALS functional rating scale-revised (ALSFRS-R) for primary outcome measure, and additional clinical findings after treatment were all collected for secondary outcome measure and safety. Age and disease-duration matched patients with ALS were selected as a control group. Results: During the follow-up period, MSCs treatment yielded a significant lesser change of ALSFRS-R score, compared to control group (1.54 vs 3.56, p<0.01). Moreover, the slop of decline of ALSFRS-R was significantly lower during the follow-up period, compared to the lead-in period in MSCs treatment group (2.68 vs 1.54, p=0.04), whereas the slopes during the two periods were not different in the control group (3.15 vs 3.56, p=0.37). MSCs treatment was well tolerated except for occurrences of transient headache, low back pain, and myalgia. Conclusions: Our results show that intrathecal MSCs injection can slow disease progression and might be used as a disease modifying modality as an alternative treatment choice in patients with ALS.
Abstract
Background: This study was performed to investigate the efficacy and safety of intrathecal autologous bone marrowderived mesenchymal stem cells (MSCs) treatment for patients with ALS. Methods: After a lead-in period for 3 months, 22 patients were treated with MSCs twice at an interval of 1 month. After initial MSCs injection, all patients were followed up for 3 months and their disease course, clinical characteristics were assessed. Disease status of patients were analyzed with ALS functional rating scale-revised (ALSFRS-R) for primary outcome measure, and additional clinical findings after treatment were all collected for secondary outcome measure and safety. Age and disease-duration matched patients with ALS were selected as a control group. Results: During the follow-up period, MSCs treatment yielded a significant lesser change of ALSFRS-R score, compared to control group (1.54 vs 3.56, p<0.01). Moreover, the slop of decline of ALSFRS-R was significantly lower during the follow-up period, compared to the lead-in period in MSCs treatment group (2.68 vs 1.54, p=0.04), whereas the slopes during the two periods were not different in the control group (3.15 vs 3.56, p=0.37). MSCs treatment was well tolerated except for occurrences of transient headache, low back pain, and myalgia. Conclusions: Our results show that intrathecal MSCs injection can slow disease progression and might be used as a disease modifying modality as an alternative treatment choice in patients with ALS.
참고문헌 (29)
- Ince PG, "Amyotrophic lateral sclerosis: current issues in classification, pathogenesis and molecular pathology", Neuropathol Appl Neurobiol, 24, pp.104~117 (1998)
- McGeer PL, "Inflammatory processes in amyotrophic lateral sclerosis", Muscle Nerve, 26, pp.459~470 (2002)
- Sargsyan SA, "Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis", Glia, 51, pp.241~253 (2005)
- Henkel JS, "Presence of dendritic cells, MCP-1, and activated microglia", macrophages in amyotrophic lateral sclerosis spinal cord tissue, 2004, pp.55, 221~235
- Appel SH, "Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis", Neurology, 71, pp.1326~1334 (2008)
- Deda H, "Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up", Cytotherapy, 11, pp.18~25 (2009)
- Silani V, "Stem-cell therapy for amyotrophic lateral sclerosis", Lancet, 364, pp.200~202 (2004)
- Mazzini L, "Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans", Amyotroph Lateral Scler Other Motor Neuron Disord, 4, pp.158~161 (2003)
- Mazzini L, "Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis", Neurol Res, 28, pp.523~526 (2006)
- Mazzini L, "Stem cell treatment in Amyotrophic Lateral Sclerosis", J Neurol Sci, 265, pp.78~83 (2008)
- Brooks BR, "El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis", Amyotroph Lateral Scler Other Motor Neuron Disord, 1, pp.293~299 (2000)
- Stonestreet BS, "Effects of acute hyperosmolality on blood-brain barrier function in ovine fetuses and lambs", Am J Physiol Regul Integr Comp Physiol, 291, pp.R1031~R1039 (2006)
- 김현영, "한글판 Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised : 신뢰도와 타당도에 관한 예비연구", 대한신경과학회지, 25(2), pp.149~154 (2007), 대한신경과학회
- Czyz J, "Potential of embryonic and adult stem cells in vitro", Biol Chem, 384, pp.1391~1409 (2003)
- Amariglio N, "Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient", PLoS Med, 6, pp.e1000029~ (2009)
- Kim DH, "Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell", Cytokine, 31, pp.119~126 (2005)
- Majumdar MK, "Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages", J Hematother Stem Cell Res, 9, pp.841~848 (2000)
- Majumdar MK, "Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells", J Cell Physiol, 176, pp.57~66 (1998)
- Dormady SP, "Immortalized multipotential mesenchymal cells and the hematopoietic microenvironment", J Hematother Stem Cell Res, 10, pp.125~140 (2001)
- Devine SM, "Mesenchymal stem cells: stealth and suppression", Cancer J, 7(2), pp.S76~S82 (2001)
- Lee JK, "Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model", Neurosci Lett, 450, pp.136~141 (2009)
- Slavin S, "The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders", Clin Neurol Neurosurg, 110, pp.943~946 (2008)
- Zietlow R, "Human stem cells for CNS repair", Cell Tissue Res, 331, pp.301~322 (2008)
- Liu CH, "Cytokine interactions in mesenchymal stem cells from cord blood", Cytokine, 32, pp.270~279 (2005)
- Gadient RA, "Interleukin-6 (IL-6)--a molecule with both beneficial and destructive potentials", Prog Neurobiol, 52, pp.379~390 (1997)
- Fattori E, "IL-6 expression in neurons of transgenic mice causes reactive astrocytosis and increase in ramified microglial cells but no neuronal damage", Eur J Neurosci, 7, pp.2441~2449 (1995)
- Kassis I, "Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis", Arch Neurol, 65, pp.753~761 (2008)
- Parr AM, "Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury", Bone Marrow Transplant, 40, pp.609~619 (2007)
- Janson CG, "Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis", J Hematother Stem Cell Res, 10, pp.913~915 (2001)