Intrahippocampal Transplantation of Undifferentiated Human Chorionic- Derived Mesenchymal Stem Cells Does Not Improve Learning and Memory in the Rat Model of Sporadic Alzheimer Disease

Author(s): Alireza Mohammadi, Ali Maleki-Jamshid, Peiman Brouki Milan, Kaveh Ebrahimzadeh, Faezeh Faghihi, Mohammad Taghi Joghataei*

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 2 , 2019

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Background and Objective: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder with consequent cognitive impairment and behavioral deficits. AD is characterized by loss of cholinergic neurons and the presence of beta-amyloid protein deposits. Stem cell transplantation seems to be a promising strategy for regeneration of defects in the brain.

Method: One of the suitable type of stem cells originated from fetal membrane is Chorion-derived Mesenchymal Stem Cells (C-MSCs). MSCs were isolated from chorion and characterized by Flowcytometric analysis. Then C-MSCs labeled with DiI were transplanted into the STZ induced Alzheimer disease model in rat.

Results: Nissl staining and behavior test were used to assess the efficacy of the transplanted cells. Phenotypic and Flowcytometric studies showed that isolated cells were positive for mesenchymal stem cell marker panel with spindle like morphology.

Conclusion: Learning and memory abilities were not improved after stem cell transplantation. C-MSCs transplantation can successfully engraft in injured site but the efficacy and function of transplanted cells were not clinically satisfied.

Keywords: Alzheimer's disease, hippocampus, chorion, transplantation, mesenchymal stem cells, neurodegenerative disorder.

Palop JJ, Mucke L. Amyloid-[beta]-induced neuronal dysfunction in Alzheimer’s disease: From synapses toward neural networks. Nat Neurosci 2010; 13(7): 812-8.
Reitz C, Brayne C, Mayeux R. Epidemiology of alzheimer disease. Nat Rev Neurol 2011; 7(3): 137-52.
Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature 2004; 430(7000): 631.
Kondo A, Shahpasand K, Mannix R, et al. Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy. Nature 2015; 523(7561): 431-6.
Nakao N, Shintani-Mizushima A, Kakishita K, Itakura T. Transplantation of autologous sympathetic neurons as a potential strategy to restore metabolic functions of the damaged nigrostriatal dopamine nerve terminals in Parkinson’s disease. Brain Res Rev 2006; 52(2): 244-56.
Hunsberger JG, Rao M, Kurtzberg J, et al. Accelerating stem cell trials for Alzheimer’s disease. Lancet Neurol 2016; 15(2): 219-30.
Roy NS, Wang S, Jiang L, et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med 2000; 6(3): 271.
Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS. Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer’s disease mice by modulation of immune responses. Stem Cells 2010; 28(2): 329-43.
Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 2000; 18(6): 675-9.
Li LY, Li JT, Wu QY, et al. Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model of Alzheimer’ disease. J Mol Neurosci 2008; 34(2): 157-63.
Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature 2006; 441(7097): 1094-6.
Zhang H, Huang Z, Xu Y, Zhang S. Differentiation and neurological benefit of the mesenchymal stem cells transplanted into the rat brain following intracerebral hemorrhage. Neurol Res 2006; 28(1): 104-12.
Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 2006; 198(1): 54-64.
Yoo SW, Kim SS, Lee SY, et al. Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model. Exp Mol Med 2008; 40(4): 387-97.
Hamada H, Kobune M, Nakamura K, et al. Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy. Cancer Sci 2005; 96(3): 149-56.
Dezawa M. Systematic neuronal and muscle induction systems in bone marrow stromal cells: the potential for tissue reconstruction in neurodegenerative and muscle degenerative diseases. Med Mol Morphol 2008; 41(1): 14-9.
Abumaree M, Al Jumah M, Kalionis B, et al. Phenotypic and functional characterization of mesenchymal stem cells from chorionic villi of human term placenta. Stem Cell Rev 2013; 9(1): 16-31.
Mohammadi A, Maleki-Jamshid A, Sanooghi D, et al. Transplantation of human chorion-derived cholinergic progenitor cells: a novel treatment for neurological disorders. Mol Neurobiol 2018. [Epub ahead of print].
Amini N, Vousooghi N, Hadjighassem M, et al. Efficacy of human adipose tissue-derived stem cells on neonatal bilirubin encephalopathy in rats. Neurotox Res 2016; 29(4): 514-24.
Sekiya I, Vuoristo JT, Larson BL, Prockop DJ. In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis. Proc Natl Acad Sci USA 2002; 99(7): 4397-402.
Bartus RT. On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol 2000; 163(2): 495-529.
Row BW, Kheirandish L, Cheng Y, Rowell PP, Gozal D. Impaired spatial working memory and altered choline acetyltransferase (CHAT) immunoreactivity and nicotinic receptor binding in rats exposed to intermittent hypoxia during sleep. Behav Brain Res 2007; 177(2): 308-14.
Arsenijevic Y, Villemure J-G, Brunet J-F, et al. Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Exp Neurol 2001; 170(1): 48-62.
Ernst A, Alkass K, Bernard S, et al. Neurogenesis in the striatum of the adult human brain. Cell 2014; 156(5): 1072-83.
Lindvall O. Dopaminergic neurons for Parkinson’s therapy. Nat Biotechnol 2012; 30(1): 56-8.
Goldman SA. Stem and progenitor cell-based therapy of the central nervous system: hopes, hype, and wishful thinking. Cell Stem Cell 2016; 18(2): 174-88.
Blurton-Jones M, Kitazawa M, Martinez-Coria H, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA 2009; 106(32): 13594-9.
Park D, Lee HJ, Joo SS, et al. Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction. Exp Neurol 2012; 234(2): 521-6.
Zhang W, Wang P-J, Sha H-Y, Ni J, Li M-H, Gu G-J. Neural stem cell transplants improve cognitive function without altering amyloid pathology in an APP/PS1 double transgenic model of Alzheimer’s disease. Mol Neurobiol 2014; 50(2): 423-37.
Kadoshima T, Sakaguchi H, Eiraku M. Telencephalic tissue formation in 3D stem cell culture Organ regeneration based on developmental biology. Springer 2017; pp. 1-24.
Sharma M, Gupta YK. Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci 2001; 68(9): 1021-9.
Strauss ME, Reynolds KS, Jayaram G, Tune LE. Effects of anticholinergic medication on memory in schizophrenia. Schizophr Res 1990; 3(2): 127-9.
Gu G, Zhang W, Li M, Ni J, Wang P. Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice. Neuroscience 2015; 291: 81-92.
Isakova IA, Baker K, DuTreil M, Dufour J, Gaupp D, Phinney DG. Age- and dose-related effects on MSC engraftment levels and anatomical distribution in the central nervous systems of nonhuman primates: identification of novel MSC subpopulations that respond to guidance cues in brain. Stem Cells 2007; 25(12): 3261-70.
DePaul MA, Palmer M, Lang BT, et al. Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury. Sci Rep 2015; 5: 16795.
Liu X, Ye R, Yan T, et al. Cell based therapies for ischemic stroke: from basic science to bedside. Prog Neurobiol 2014; 115: 92-115.
Lang BT, Cregg JM, DePaul MA, et al. Modulation of the proteoglycan receptor PTP [sgr] promotes recovery after spinal cord injury. Nature 2015; 518(7539): 404-8.
Rosado-de-Castro PH, Schmidt FR, Battistella V, et al. Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. Regen Med 2013; 8(2): 145-55.
Ridley R, Baker J, Baker H, Maclean C. Restoration of cognitive abilities by cholinergic grafts in cortex of monkeys with lesions of the basal nucleus of Meynert. Neuroscience 1994; 63(3): 653-66.
Yun H, Kim H, Park K, et al. Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1–42-infused mouse model of Alzheimer’s disease. Cell Death Dis 2013; 4(12): e958.
Darsalia V, Allison SJ, Cusulin C, et al. Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain. J Cereb Blood Flow Metab 2011; 31(1): 235-42.

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Article Details

Year: 2019
Page: [184 - 190]
Pages: 7
DOI: 10.2174/1574888X13666180723111249
Price: $65

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