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Current Stem Cell Research & Therapy


ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Cell-based Treatment of Cerebral Palsy: Still a Long Way Ahead

Author(s): Mohammad Shariati, Reza Jafarzadeh Esfahani, Hamid Reza Bidkhori, Ehsan Sabouri, Shadi Mehrzad and Ariane Sadr-Nabavi*

Volume 17, Issue 8, 2022

Published on: 07 December, 2021

Page: [741 - 749] Pages: 9

DOI: 10.2174/1574888X16666211102090230

Price: $65


Background: Cerebral palsy (CP) is a permanent neurodevelopmental disorder with considerable global disability. Various rehabilitation strategies are currently available. However, none represents a convincing curative result. Cellular therapy recently holds much promise as an alternative strategy to repair neurologic defects.

Method: In this narrative review, a comprehensive search of the MEDLINE and was made, using the terms: “cell therapy” and “cerebral palsy”, including published and registered clinical studies, respectively.

Results: The early effects of these studies demonstrated that using cell therapy in CP patients is safe and improves the deficits for a variable duration. Despite such hopeful early bird results, the long-term outcomes are not conclusive.

Conclusions: Due to the heterogeneous nature of CP, personal factors seem essential to consider. Cell dosage, routes of administration, and repeated dosing are pivotal to establish optimal personalized treatments. Future clinical trials should consider employing other cell types, specific cell modifications before administration, and cell-free platforms.

Keywords: Cerebral palsy, cell therapy, clinical trial, cell-based therapy, stem cells, regenerative medicine.

Stavsky M, Mor O, Mastrolia SA, Greenbaum S, Than NG, Erez O. Cerebral palsy-trends in epidemiology and recent development in prenatal mechanisms of disease, treatment, and prevention. Front Pediatr 2017; 5: 21.
[] [PMID: 28243583]
Rosenbaum P, Paneth N, Leviton A, et al. A report: The definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl 2007; 109: 8-14.
[PMID: 17370477]
Hai-Jing W, Qian Y. A review of the treatment of cerebral palsy in children. 2018; 1(4): 151-8.
Parizadeh S M, Jafarzadeh-Esfehani R, Ghandehari M, et al. Stem cell therapy: A novel approach for myocardial infarction. J Cell Physiol 2019; 234(10): 16904-12.
[] [PMID: 30811054]
Parizadeh SM, Jafarzadeh-Esfehani R, Hassanian SM, et al. Targeting cancer stem cells as therapeutic approach in the treatment of colorectal cancer. Int J Biochem Cell Biol 2019; 110: 75-83.
[] [PMID: 30818083]
Mazini L, Rochette L, Amine M, Malka G. Regenerative capacity of Adipose Derived Stem Cells (ADSCs), comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci 2019; 20(10): E2523.
[] [PMID: 31121953]
Mastrolia I, Foppiani EM, Murgia A, et al. Challenges in clinical development of mesenchymal stromal/stem cells: Concise review. Stem Cells Transl Med 2019; 8(11): 1135-48.
[] [PMID: 31313507]
Kupcova Skalnikova H. Proteomic techniques for characterisation of mesenchymal stem cell secretome. Biochimie 2013; 95(12): 2196-211.
[] [PMID: 23880644]
Andrzejewska A, Lukomska B, Janowski M. Concise review: Mesenchymal stem cells: From roots to boost. Stem Cells 2019; 37(7): 855-64.
[] [PMID: 30977255]
Kucia M, Reca R, Jala VR, Dawn B, Ratajczak J, Ratajczak MZ. Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells. Leukemia 2005; 19(7): 1118-27.
[] [PMID: 15902288]
Mukai T, Tojo A, Nagamura-Inoue T. Mesenchymal stromal cells as a potential therapeutic for neurological disorders. Regen Ther 2018; 9: 32-7.
[] [PMID: 30525073]
Bansal H, Singh L, Verma P, et al. Administration of autologous bone marrow-derived stem cells for treatment of cerebral palsy patients: A proof of concept. J Stem Cells 2016; 11(1): 37-49.
[PMID: 28296863]
Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M. Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Case Rep Transplant 2012; 2012: 825289.
[] [PMID: 23259143]
Koh H, Hwang K, Lim HY, Kim YJ, Lee YH. Mononuclear cells from the cord blood and granulocytecolony stimulating factor-mobilized peripheral blood: Is there a potential for treatment of cerebral palsy? Neural Regen Res 2015; 10(12): 2018-24.
[] [PMID: 26889193]
Liu L, Eckert MA, Riazifar H, Kang DK, Agalliu D, Zhao W. From blood to the brain: Can systemically transplanted mesenchymal stem cells cross the blood-brain barrier? Stem Cells Int 2013; 2013: 435093.
[] [PMID: 23997771]
Moon J H, Kim M J, Song S Y, et al. Safety and efficacy of G-CSF mobilization and collection of autologous peripheral blood stem cells in children with cerebral palsy. Transfus Apher Sci 2013; 39(3): 516-21.
Toth ZE, Leker RR, Shahar T, et al. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia. Blood 2008; 111(12): 5544-52.
[] [PMID: 18268092]
Papadopoulos KI, Low SS, Aw TC, Chantarojanasiri T. Safety and feasibility of autologous umbilical cord blood transfusion in 2 toddlers with cerebral palsy and the role of low dose granulocyte- colony stimulating factor injections. Restor Neurol Neurosci 2011; 29(1): 17-22.
[] [PMID: 21335665]
Kang M, Min K, Jang J, et al. Involvement of immune responses in the efficacy of cord blood cell therapy for cerebral palsy. Stem Cells Dev 2015; 24(19): 2259-68.
[] [PMID: 25977995]
Lee YH, Choi KV, Moon JH, et al. Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy. J Transl Med 2012; 10: 58.
[] [PMID: 22443810]
Fan CG, Zhang QJ, Tang FW, Han ZB, Wang GS, Han ZC. Human umbilical cord blood cells express neurotrophic factors. Neurosci Lett 2005; 380(3): 322-5.
[] [PMID: 15862910]
Chen G, Wang Y, Xu Z, et al. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy. J Transl Med 2013; 11: 21.
[] [PMID: 23351389]
Nguyen LT, Nguyen AT, Vu CD, Ngo DV, Bui AV. Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: An open label uncontrolled clinical trial. BMC Pediatr 2017; 17(1): 104.
[] [PMID: 28403842]
Liu X, Fu X, Dai G, et al. Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy. J Transl Med 2017; 15(1): 48.
[] [PMID: 28235424]
Silbereis JC, Huang EJ, Back SA, Rowitch DH. Towards improved animal models of neonatal white matter injury associated with cerebral palsy. Dis Model Mech 2010; 3(11-12): 678-88.
[] [PMID: 21030421]
Akiyama Y, Radtke C, Honmou O, Kocsis JD. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 2002; 39(3): 229-36.
[] [PMID: 12203389]
Aloisi F. Immune function of microglia. Glia 2001; 36(2): 165-79.
[] [PMID: 11596125]
Boomsma RA, Geenen DL. Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis. PLoS One 2012; 7(4): e35685.
[] [PMID: 22558198]
McLauchlan D, Robertson NP. Stem cells in the treatment of central nervous system disease. J Neurol 2018; 265(4): 984-6.
[] [PMID: 29523970]
Jiao Y, Li XY, Liu J. A new approach to cerebral palsy treatment: Discussion of the effective components of umbilical cord blood and its mechanisms of action. Cell Transplant 2019; 28(5): 497-509.
[] [PMID: 30384766]
Jafarzadeh-Esfehani R, Soudyab M, Parizadeh SM, et al. Circulating exosomes and their role in stroke. Curr Drug Targets 2020; 21(1): 89-95.
[] [PMID: 31433753]
Parizadeh SM, Jafarzadeh-Esfehani R, Ghandehari M, et al. Circulating exosomes as potential biomarkers in cardiovascular disease. Curr Pharm Des 2018; 24(37): 4436-44.
[] [PMID: 30569849]
Kim DK, Nishida H, An SY, Shetty AK, Bartosh TJ, Prockop DJ. Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proc Natl Acad Sci USA 2016; 113(1): 170-5.
[] [PMID: 26699510]
Drommelschmidt K, Serdar M, Bendix I, et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav Immun 2017; 60: 220-32.
[] [PMID: 27847282]
Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 2008; 103(11): 1204-19.
[] [PMID: 19028920]
Chernykh ER, Kafanova MY, Shevela EY, et al. Clinical experience with autologous M2 macrophages in children with severe cerebral palsy. Cell Transplant 2014; 23(Suppl. 1): S97-S104.
[] [PMID: 25302537]
Huang L, Zhang C, Gu J, et al. A randomized, placebo-controlled trial of human umbilical cord blood mesenchymal stem cell infusion for children with cerebral palsy. Cell Transplant 2018; 27(2): 325-34.
[] [PMID: 29637820]
Sun JM, Song AW, Case LE, et al. Effect of autologous cord blood infusion on motor function and brain connectivity in young children with cerebral palsy: A randomized, placebo-controlled trial. Stem Cells Transl Med 2017; 6(12): 2071-8.
[] [PMID: 29080265]
Rah WJ, Lee YH, Moon JH, et al. Neuroregenerative potential of intravenous G-CSF and autologous peripheral blood stem cells in children with cerebral palsy: A randomized, double-blind, cross-over study. J Transl Med 2017; 15(1): 16.
[] [PMID: 28109298]
Min K, Song J, Kang JY, et al. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: A double-blind, randomized, placebo-controlled trial. Stem Cells 2013; 31(3): 581-91.
[] [PMID: 23281216]
Dong H, Li G, Shang C, et al. Umbilical Cord Mesenchymal Stem Cell (UC-MSC) transplantations for cerebral palsy. Am J Transl Res 2018; 10(3): 901-6.
[PMID: 29636880]
Wang X, Hu H, Hua R, et al. 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 2015; 17(2): 224-31.
[] [PMID: 25593078]
Zali A, Arab L, Ashrafi F, et al. Intrathecal injection of CD133- positive enriched bone marrow progenitor cells in children with cerebral palsy: Feasibility and safety. Cytotherapy 2015; 17(2): 232-41.
[] [PMID: 25593079]
Nguyen TL, Nguyen HP, Nguyen TK. The effects of bone marrow mononuclear cell transplantation on the quality of life of children with cerebral palsy. Health Qual Life Outcomes 2018; 16(1): 164.
[] [PMID: 30107811]
Thanh LN, Trung KN, Duy CV, et al. Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: An open-label, uncontrolled clinical trial. BMC Pediatr 2019; 19(1): 290.
[] [PMID: 31438885]
Englander ZA, Sun J, Laura Case , Mikati MA, Kurtzberg J, Song AW. Brain structural connectivity increases concurrent with functional improvement: Evidence from diffusion tensor MRI in children with cerebral palsy during therapy. Neuroimage Clin 2015; 7: 315-24.
[] [PMID: 25610796]
Wang SS, Jia J, Wang Z. Mesenchymal stem cell-derived extracellular vesicles suppresses iNOS expression and ameliorates neural impairment in Alzheimer’s disease mice. J Alzheimers Dis 2018; 61(3): 1005-13.
[] [PMID: 29254100]
Elia CA, Tamborini M, Rasile M, et al. Intracerebral injection of extracellular vesicles from mesenchymal stem cells exerts reduced Aβ plaque burden in early stages of a preclinical model of Alzheimer’s disease. Cells 2019; 8(9): E1059.
[] [PMID: 31510042]
Han M, Cao Y, Xue H, et al. Neuroprotective effect of mesenchymal stromal cell-derived extracellular vesicles against cerebral ischemia-reperfusion-induced neural functional injury: A pivotal role for AMPK and JAK2/STAT3/NF-κB signaling pathway modulation. Drug Des Devel Ther 2020; 14: 2865-76.
[] [PMID: 32764885]
Zhou X, Chu X, Yuan H, et al. Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis. Biomed Pharmacother 2019; 115: 108818.
Wyse RD, Dunbar GL, Rossignol J. Use of genetically modified mesenchymal stem cells to treat neurodegenerative diseases. Int J Mol Sci 2014; 15(2): 1719-45.
[] [PMID: 24463293]
Sharma A, Sane H, Kulkarni P, D’sa M, Gokulchandran N, Badhe P. Improved quality of life in a case of cerebral palsy after bone marrow mononuclear cell transplantation. Cell J 2015; 17(2): 389-94.
[PMID: 26199918]
Mancías-Guerra C, Marroquín-Escamilla AR, González-Llano O, et al. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: An open-label phase I trial. Cytotherapy 2014; 16(6): 810-20.
[] [PMID: 24642016]
Wang X, Cheng H, Hua R, et al. Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: A preliminary clinical study. Cytotherapy 2013; 15(12): 1549-62.
[] [PMID: 24100132]

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