Intrathecal Autologous Bone Marrow Derived MSC Therapy in Cerebral Palsy: Safety and Short Term Efficacy
American Journal of Bioscience and Bioengineering
Volume 3, Issue 4-1, July 2015, Pages: 24-29
Received: May 29, 2015; Accepted: Jun. 1, 2015; Published: Jun. 30, 2015
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Authors
Hala Gabr, Hematology, Faculty of Medicine, Cairo University, Cairo, Egypt
Wael Abou El-Kheir, Immunology, Military Medical Academy, Cairo, Egypt
Osama Ghannam, Neurosurgery, Faculty of Medicine, Azhar university, Cairo, Egypt
Mohamed Esewy El-Fiki, Neurosurgery, Faculty of Medicine, Alexandria University, Cairo, Egypt
Yehia Salah, Anaesthesia, Military Medial Academy, Cairo, Egypt
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Abstract
Objectives: Cerebral palsy (CP) is a disorder caused by injury or abnormal development of the brain at or immediately after birth. Current management of CP may improve the symptoms, such as muscle tone and gait, but is not directed to the original damage. Cellular therapy is evolving as a regenerative tool in many diseases with neural damage. Mesenchymal stem cells (MSCs) have been proven to transdifferentiate into neural lineage and improve neurodegeneration in animal models and in few clinical trials. This study was designed to evaluate the safety and efficacy of autologous MSC therapy in cases of CP. Subjects and Methods: this study is a randomized controlled trial enrolling 100 CP patients aged 1-7 years. Patients were assigned into two groups: Study group (44 patients after drop out cases) and control group (50 patients). All patients were subjected to history taking and clinical assessment. The study groups underwent bone marrow aspiration and MSC separation. MSCs were injected intrathecally. Follow-up was done using Child Health Questionnaire, Gross Motor Function classification System and Pediatric evaluation of disability inventory. Results: Overall assessment revealed improvement in motor, cognitive, or social parameters in 8 patients (18.18%). Study group showed improvement in Child Health Questionnaire, Gross Motor Function Classification, but not Pediatric Evaluation of Disablity Inventory. No correlation was found between improvement and age or gender. Complications observed were transient related to injection, no neurological or radiological complications were observed. Conclusions: Autologous MSC injection in CP patients showed short-term safety, with variable efficacy in improving motor and cognitive defects.
Keywords
Cerebral Palsy, Cellular Therapy, Mesenchymal Stem Cells, Neuroregeneration
To cite this article
Hala Gabr, Wael Abou El-Kheir, Osama Ghannam, Mohamed Esewy El-Fiki, Yehia Salah, Intrathecal Autologous Bone Marrow Derived MSC Therapy in Cerebral Palsy: Safety and Short Term Efficacy, American Journal of Bioscience and Bioengineering. Special Issue: Stem Cells for Neuro-Regeneration: Where Do We Stand. Vol. 3, No. 4-1, 2015, pp. 24-29. doi: 10.11648/j.bio.s.2015030401.14
References
[1]
Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D, Dan B and Jacobsson B (2007): A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl;109:8-14.
[2]
Koman LA, Smith BP, Shilt JS.(2004): Cerebral palsy. Lancet;363:1619-31.
[3]
Achache V, Roche N, Lamy J-C, Boakye M, Lackmy A, Gastal A, Quentin V and Katz R.(2010): Transmission within several spinal pathways in adults with cerebal palsy. Brain 133(5):1470-1483.
[4]
Wu Y, Xing G, Fuentes-Afflick E, Danielson B, Smith L, and Gilbert W. (2011): Racial, Ethnic and Socioeconomic disparities in the prevalence of cerebral palsy. Pediatrics , 127:e674-e681.
[5]
Moreno-De-Luca A, Ledbetter DH, Martin CL. (2012) : Genetic insights into the causes and classification of the cerebral palsies. Lancet Neurol 11(3):283–92.10.1016/S1474-4422(11)70287-3.
[6]
Hermansen MC, Hermansen MG(2006): Perinatal Infections and Cerebral Palsy. Clin Perinatol 33:315-333.
[7]
Oskouni M, Coutinho F, Dykeman J, Jette N, Pringshein T. (2013): An update on the prevalence of cerebral palsy: a systematic review and meta-analysis. Dev Med Child Neurol. 55(6):509-19.
[8]
Basu AP and Clowry G (2015): Improving Outcomes in Cerebral palsy with early intervention: New translational approaches. Front Neurol 6:24.
[9]
Corry IS, Cosgrove AP, Duffy CM, Taylor TC, Graham HK (1999): Botulinum toxin A in hamstring spasticity. Gait Posture 10;206-210.
[10]
Vaughan CL, Subramanian N, Busse ME (1998): Selective dorsal rhizotomy as a treatment option for children with spastic cerebral palsy. Gait Posture 8:43-59.
[11]
Albright AL (1996): Intrathecal baclofen in cerebral palsy movement disorders. J Child Neurol 11:S29-S35.
[12]
Drobyshevsky A, Cotten CM, Shi Z, Luo K, Jiang R,Derrick M, Tracy ET, Gentry T, Goldberg RN, Kurtzberg J, Tan S (2015): Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model. Dev Neurosci
[13]
Zhang L, Li Y,Zhang C, Chopp M, Gosiewska A, Hong K (2011): Delayed administration of human umbilical tissue-derived cells improved neurological functional recovery in a rodent model of focal ischemia. Stroke 42:1437-1444.
[14]
Aly H, Mohsen I, Badrawi N, Gabr H, Aly Z, Akmal D (2011): Viability an neural differentiation of mesenchymal stem cells derived from the umbilical cord in perinatal hypoxia. J Perinatol 1-6.
[15]
Landgraf JM, Abetz L, Ware JE (1996): Child health questionnaire (CHQ): a user's manual. Boston: The Health Institute. New England Medical Centre.
[16]
Palisano BR Rosenbaum BP, Walter BS, Russel, D, Wood E, Galuppi B(1997): Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 39:2214-223.
[17]
Haley SM: Pediatric evaluation of disability inventory (PEDI) (1992): development, standardization, and administration manual. Boston: New England Medical Center Hospital, PEDI Research Group.
[18]
Wu YW, Xing G, Fuentes-Afflick E, Danielson B, Smith LH, Gilbert WM (2011): Racial, Ethnic, and socioeconomic disparities in the prevalence of cerebral palsy. Pediatrics 127(3):e674-681.
[19]
Kassis I, Grigoriadis N, Gowda-Kurkalli B, Mizrachi-Kol R, Ben-Hur T, Slavin S, Abramsky O, Darussis D(2008).: Neuroprotection and Immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol. 65(6):753-761.
[20]
Ilic D and Polak JM.(2011): Stem cells in regenerative medicine: introduction. Br Med Bull 98 (1): 117-126.
[21]
Banerjee S, Williamson D, Habib N, Gordon M, Chataway J (2011): Human stem cell therapy in ischaemic stroke: a review. Age Ageing 40 (1): 7-13.
[22]
Hyun JK, and Kim HW (2010): Clinical and Experimental Advances in Regeneration of Spinal Cord Injury. J Tissue Eng Jan-Dec.
[23]
Vale S (2008): Current management of the cognitive dysfunction in Parkinson's Disease: How far have we come? Exp Biol Med 233 (8): 941-951.
[24]
Cameron SH, Alwakeel AJ, Goddard L, Hobbs CE, Gowing EK, Barnett ER, Kohe, SE, Sizemore RJ, Oorscho DE (2015): Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia. Mol Cel Neurosc doi:10.1016/j.mcn.2015.03.019.
[25]
Hass R, Kasper C, Bohm S and Jacobs R (2011): Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Sig 9:12.
[26]
Dominici, M., K. Le Blanc, I. Mueller, I. Slaper-Cortenbach, F. Marini, D. Krause, R. Deans, A. Keating, D. Prockop, E. Horwitz: Minimal criteria for defining multipotent mesenchymal stromal cells: The International Society for Cellular Therapy position statement. Cytotherapy 8: 315-317 (2006).
[27]
McCullough N and Parkes J: Use of the Child Health Questionnaire in Children with Cerebral palsy: a Systematic Review and Evaluation of the Psychometric Properties. J Pediatr. Psychol. 33:80-90 (2008).
[28]
Vitale MG, Roye AE, Choe JC, Heymann JE, Ley FY, Roye DP: Assessment of health status in children with cerebral palsy: What is the role of quality of life measures. Journal of Pediatric Orthopedics 25(6): 792-797.
[29]
Romanov YA, Tarakanov OP, Radaev SM, Dugina TN, Ryaskina SS, Darevskya AN, Morozova YV, Khachatryan WA, Lebedev KE, Zotova NS, Burkova AS, Sukhikh GT, Smirnov VN (2015): Huan allogeneic ABO/Rh-identical umbilical cord blood cells in the treatment of juvenile patients with cerebral palsy. Cytotherapy S1465-3249(15)00074-2. doi:
[30]
Sharma A, Sane H, Gokulchandran N, Kulkarni P, Gandhi S, Sundaram J, Paranjape A, Shetty A, Bhagwanani K, biju H, Badhe P (2015): A clinical study of autologous bone marrow mononuclear cells for cerebral palsy patients: a new frontier. Stem Cells Int 2015:905874.
[31]
Zali A, Arab L, Ashrafi F, Mardpour s,Niknejhadi M, Hedayati-Asl AA, Halimi-Asl A, Ommi D, Hosseini SE, Baharvand H,Aghdami N (2015): Intrathecal injection of CD133-positive enriched bone marrow progenitor cells in children with cerebral palsy: feasibility and safety. Cytotherapy 17(2):232- 41.
[32]
Wang X, Hu H, Hua R, Yang J, Zheng P, Niu X, Cheng H, Dai G, Liu X, Zhang Z, An Y (2015): Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors. Cytotherapy 17(2):224-31.
[33]
Shroff G, Gupta A, Barthakur J (2014): Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy. J Transl Med 12(1):318.
[34]
Mancieas-Gurerra C, Marroquin-Escamilla AR, Gonzalez-Llano O, Villarreal-Martinez L, Jaime-Perez JC, Garca-Rodriguez F, Valdes-Burnes SL, Rodriguiez-Romo lN, Barrera-Morales DC, Sanchez-Hernandez JJ, Cantu-Rodriguez OG, Gutierrez-Aguirre CH, Gomez-De Leon A, Elizondo-Riojas G, Salazar-Riojas R, Gomez-Almaguer D (2014): Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial. Cytotherapy 16(6):810-20.
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