Mesenchymal Stem Cells in Neurodegenerative Diseases

Yıl 2015, Cilt: 24 Sayı: 1, 41 - 55, 17.11.2014

Olcay Ergürhan Kıroğlu , Fazilet Aksu

https://doi.org/10.17827/aktd.27586

Öz

Neurodegenerative diseases are almost incurable, debilitating, and they might be fatal, because of limited neurogenesis in nervous system, presence of inhibitory substances and inhibition of recovery due to development of glial scar. Despite many treatment strategies of neurodegenerative diseases no full cure has been achieved. The successful results for mesenchymal stem cells applications on muscles, heart and liver diseases and the application of these cells to the damaged area in particular, hypoxia, inflammation and apoptosis promise hope of using them for neurodegenerative diseases. Mesenchymal stem cells applications constitute a vascular and neuronal phenotype in Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis and Alzheimer's disease. Stem cells release bioactive agents that lead to suppression of local immune system, reduction of free radicals, increase in angiogenesis, inhibition of fibrosis, and apoptosis. In addition, tissue stem cells, increase neuronal healing, stimulate proliferation and differentiation. These findings show that stem cells might be a hope of a cure in the treatment of neurodegenerative diseases and intensive work on this issue should continue.

Anahtar Kelimeler

Mesenchymal stem cells, therapy, neurodegenerative disease

Nörodejeneratif Hastalıklarda Mezenkimal Kök Hücre Uygulamaları

Öz

Nörodejeneratif hastalıkların tedavisi oldukça güçtür ve bazen de öldürücüdür. Bunun nedeni santral sinir sisteminde nörogenesisin sınırlı olması, aktif inhibitör maddelerin bulunması ve glial skar dokusunun gelişmesi nedeniyle iyileşmenin engellenmesidir. Nörodejeneratif hastalıkların tedavisinde birçok uygulama yapılmasına rağmen tam bir kür elde etmek mümkün olmamıştır. Mezenkimal kök hücre uygulamalarının kas, kalp ve karaciğer gibi çeşitli doku hasarlarında uygulanması sonucu bu hücrelerin hasarlı bölgeye özellikle hipoksik, inflamasyonlu ve apoptotik alanlara yerleşerek dokunun rejenenarasyon ve tamirini oluşturduğunun gözlenmesi nörodejeneratif hastlıkların tedavisi için de bir umut olmuştur. Parkinson hastalığı, Huntington hastalığı, Amyotrofik lateral skleroz ve Alzheimer hastalığı gibi beyin ve spinal kanalda nöron ve glial hücre kaybıyla seyreden ve tedavi olasılığı çok sınırlı olan nörodejenaratif hastalıklarda uygulanan mezenkimal kök hücreler hasarlı bölgede nöronal ve vasküler fenotip oluşturmaktadır. Uygulanan kök hücreler biyoaktif maddeler salarak lokal immun sistemin baskılanmasını, anjiogenezin artmasını, serbest radikallerin azalmasını, fibrozis ve apoptozisin inhibisyonunu sağlamaktadır. Ayrıca dokuda bulunan kök hücreler, nöronal iyileşmeyi, çoğalmayı ve farklılaşmayı uyarmaktadır. Bu bulgular nörodejeneratif hastalıkların tedavisinde kök hücre uygulamalarının ciddi bir tedavi umudu olabileceğini ve bu konudaki çalışmaların yoğun bir şekilde devam etmesi gerektiğini bize göstermektedir.

Anahtar Kelimeler

Mezenkimal kök hücre, tedavi, nörodejeneratif hastalıklar

Kaynakça

• Williams JT, Southerland SS, Souza J. Cells isolated from adult human skeletal musclecapable of differentiating into multiple mesodermal phenotypes. Am Surg. 1999;65:22–6.
• Galmiche MC, Koteliansky VE, Briere J. Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway. Blood. 1993;82:66–76.
• Theise ND, Nimmakayalu M, Gardner R. Liver from bone marrow in humans. Hepatology. 2000;32:11–6.
• Theise ND, Badve S, Saxena R. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 2000;31:235–40.
• Orlic D, Kajstura J, Chimenti S. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–5.
• Wu GD, Nolta JA, Jin YS. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation. 2003;75:679–85.
• Davidoff AM, Ng CY, Brown P. Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growthin mice. Clin Cancer Res. 2001;7:2870–9.
• Crisa L, Cirulli V, Smith KA. Human cord blood progenitors sustain thymic T-cell development and a novel form of angiogenesis. Blood. 199;94:3928–40.
• Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M et al. Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol. 2004;287:2670-6.
• Huang W, Mo X, Qin C, Zheng J, Liang Z, Zhang C. Transplantation of differentiated bone marrow stromal cells promotes motor functional recovery in rats with stroke. Neurol Res.2013; 35:320-8.
• Murphy JM, Fink DJ, Hunziker EB. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48:3464–74.
• Das AK. Stem cell therapy for critical limb ischaemia. Indian J Surg. 2009;71:177-81.
• Hess DC, Borlongan CV. Stem cells and neurological diseases. Cell Prolif. 2008;1:94-114.
• Brockes JP. Amphibian limb regeneration: rebuilding a complex structure. Science. 1997;276:81– 7.
• Brockes JP, Kumar A. Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science. 2005; 310:1919–23.
• Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313–7.
• Munoz JR,Stoutenger BR, Robinson AP. Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc Natl Acad Sci. 2005;102:18171–6.
• Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis in the neocortex of adult mice. Nature.2000;405: 951–5.
• Johansson CB. Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation. Nat Cell Biol. 2008;10:575–83.
• Nygren JM. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion. Nat Cell Biol.2000;10:584–92.
• Singec I,Snyder EY. Inflammation as a matchmaker: revisiting cell fusion. Nat Cell Biol. 2008;10:503–5.
• Neirinckx V, Cantinieaux D, Coste C, Rogister B, Franzen R, Wislet-Gendebien S. Spinal cord injuries - how could adult mesenchymal and neural crest stem cells take up the challenge?. Stem Cells. 2014;32:829-43..
• Cogle CR. Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet. 2004;363: 1432–7.
• Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci. 2003;18 2088- 93.
• Sensebé L, Bourin P, Tarte K. Good manufacturing practices production of mesenchymal stem/stromal cells. Phil Trans R Soc. 2006;361: 1463–75.
• Wang T, Tang W, Sun S, Xu T, Wang H, Guan J et al. Intravenous infusion of bone marrow mesenchymal stem cells improves brain function after resuscitation from cardiac arrest. Crit Care Med. 2008;36:486-91.
• Chung DJ, Choi CB, Lee SH, Kang EH, Lee JH, Hwang SH et al. Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia. J Neurosci Res. 2009;87:3554-67.
• Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural pogenitors in an experimental model of multiple sclerosis. J Neurol Sci. 2012;15,313:167-77.
• Sokolova IB, Sergeev IV, Bilibina AA, Dvoretskiy DP. Arteriogenesis in the pia matter of the rat brain cortex after intracerebral injection of mesenchymal stem cells. Bull Exp Biol Med. 2012;154:177-9.
• Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Nasuelli N et al. Stem cell treatment in Amyotrophic Lateral Sclerosis. J Neurol Sci. 2008;15,265:78-83.
• Kessler JA. Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Nature. 1993;362:62.
• Croitoru-Lamoury J, Lamoury FM, Zaunders JJ, Veas LA, Brew BJ. Human mesenchymal stem cells constitutively express chemokines and chemokine receptors that can be upregulated by cytokines, IFN-beta, and Copaxone. Cytokine Res. 2007;27:53-64.
• Kang KS, Kim S, Oh YH. A 37-year old spinal cord-injured female patient, transplanted of multi- potent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study. Cytotherapy. 2005;7:368-73.
• Cristofanilli M, Harris VK, Zigelbaum A, Goossens AM, Lu A, Rosenthal H et al. Mesenchymal stem cells enhance the engraftment and myelinating ability of allogeneic oligodendrocyte progenitors in dysmyelinated mice. Stem Cells. 2011;20:2065-76.
• Rao SS, Hofmann LA, Shakil A. Parkinson's disease: diagnosis and treatment Am Fam Physician. 2006; 15,74:2046-54.
• Keitel A, Ferrea S, Südmeyer M, Schnitzler A, Wojteck L. Expectation modulates the effect of deep brain stimulation on motor and cognitive function in tremor-dominant Parkinson's disease. PLoS One. 2013;2:8-12.
• Ryu MY, Lee MA, Ahn JH, Cho KG, Kim SU.Brain transplantation of genetically modified neural stem cells in parkinsonian rat. Cell Transplant. 2005;14:193–202.
• Kim SU, Park IH, Kim TH. Brain transplantationof human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase-1 provides functional improvement in animal models of Parkinson disease. Neuropathology. 2006;26:129–40.
• Kim JH, Auerbach JM, Rodríguez-Gómez JA, Velasco I, Gavin D, Lumelsky N et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature. 2002;4:50-6.
• Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature. 2011;6,480:547-51.
• Fricker-Gates RA, Gates MA. Stem cell-derived dopamine neurons for brain repair in Parkinson's diseases. Regen Med. 2010;5:267-78.
• Studer L. Derivation of dopaminergic neurons from pluripotent stem cells. Prog Brain Res. 2012;200:243–63.
• Yang B, Strong R, Sharma S, Brenneman M, Mallikarjunarao K, Xi X et al. Therapeutic time window and dose response of autologous bone marrow mononuclear cells for ischemic stroke. J Neurosci Res. 2011;89:833–9.
• Engelhardt B, Sorokin L. The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol. 2009;31:497–511.
• Redzic Z. Molecular biology of the blood–brain and the blood–cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS. 2011;8:3.
• Ourednik J, Ourednik V, Lynch WP, Schachner M, Snyder EY. Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nature Biotechnol. 2002;20:1103–10.
• Guo J, Zeng Y, Liang Y, Wang L, Su H, Wu W. Cyclosporine affects the proliferation and differentiation of neural stem cells in culture. Neuroreport. 2007;18:863–8.
• Moloney TC, Rooney GE, Barry FP, Howard L, Dowd E. Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain. Brain Res. 2010;1359:33-43.
• Rowland LP. Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med. 2001;344:1688–1700.
• Boillee S, Van de Velde C, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron. 2006;52:39–59.
• Traub R, Mitsumoto H, Rowland L. Research advances in amyotrophic lateral sclerosis. Curr Neurol Neurosci Rep. 2011;11:67–77.
• Kim SU, de Vellis J. Stem cell-based cell therapy in neurological diseases: areview. J Neurosci Res. 2009;87:2183–200.
• Lunn JS, Sakowski SA, Federici T. Stem cell technology for the study andtreatment of motor neuron diseases. Regen Med. 2011;6:201–13.
• Giordano A, Galderisi U, Marino IR. From the laboratory bench to the patient’s bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol. 2007;211:27–35.
• Chi L, Ke Y, Luo C. Motor neuron degeneration promotes neural progenitor cell proliferation, migration, and neurogenesis in the spinal cords of amyotrophic lateral sclerosis mice. Stem Cells. 2006;24:34–43.
• Mazzini L, Vercelli A, Ferrero I. Stem cells in amyotrophic lateral sclerosis:state of the art. Expert Opin Biol Ther. 2009;9:1245–58.
• Klein SM, Behrstock S, McHugh J, Hoffmann K, Wallace K, Suzuki M et al. GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum Gene Ther. 2005;16:509-21.
• Storkebaum E, Lambrechts D, Dewerchin M, Moreno-Murciano MP, Appelmans S, Oh H et al. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat Neurosci. 2005;8:85-92.
• Mazzini L, Mareschi K, Ferrero I, Miglioretti M, Stecco A, Servo Set al. Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study. Cytotherapy. 2012;14:56-60.
• O'Shea B. A review of Huntington's disease. Int J Psychiatry Clin Pract. 1997;1:135-40.
• Olson SD, Pollock K, Kambal A, Cary W, Mitchell GM, Tempkin J et all. Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington’s disease. Mol Neurobiol. 2012;45: 87-98.
• Baquet ZC, Gorski JA, Jones KR. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brainderived neurotrophic factor. J Neurosci. 2004;24:4250-8.
• Dey ND, Bombard MC, Roland BP, Davidson S, Lu M, Rossignol J et al. Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington’s disease. Behav Brain Res. 2010;214:193-200.
• Ryu JK, Kim J, Cho SJ, Hatori K, Nagai A, Choi HBet al. Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease. Neurobiol Dis. 2004;16:68-77.
• Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.
• Wenk GL. Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry. 2003;64:7–10.
• Bartus RT, Dean RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217:408-14.
• Pohanka M. Cholinesterases, a target of pharmacology and toxicology. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011;155:219–23.
• Haas C. Strategies, development, and pitfalls of therapeutic options for Alzheimer’s disease. J Alzheimers Dis. 2012;28:241–81.
• Phinney DG, Prockop DJ. Mesenchymal stem/multipotent stromal cells: The state of transdifferentiation and modes of tissue repair—Current views. Stem Cells. 2007;25:2896–2902.
• Yang H, Xie Z, Wei L, Yang H, Yang S, Zhu Z et al. Human umbilical cord mesenchymal stem cell- derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model. Stem Cell Res Ther. 2013;4:76.
• Mitran SI, Catalin B, Sfredel V, Balseanu TA. Neuroregeneration and dementia: new treatment options. J Mol Psychiatry. 2013;1:1–6.
• Musiał A, Bajda M, Malawska B. Recent developments in cholinesterases inhibitors for Alzheimer's disease treatment. Curr Med Chem. 2007;14:2654-79.
• Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Müller FJ, Loring JF et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A. 2009;106: 13594-9.
• Kim KS, Kim HS, Park JM, Kim HW, Park MK, Lee HSet al. Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer’s disease model. Neurobiol Aging. 2013;34:2408–20.
• Bae JS, Jin HK, Lee JK, Richardson JC, Carter JE. Bone marrow-derived mesenchymal stem cells contribute to the reduction of amyloid-β deposits and the improvement of synaptic transmission in a mouse model of pre-dementia Alzheimer's disease. Curr Alzheimer Res. 2013;10:524-31.
• Khairallah MI, Kassem LA, Yassin NA, El Din MA, Zekri M, Attia M. The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease. Pak J Biol Sci. 2014;17:9-21.
• Correspondence Address / Yazışma Adresi Olcay Kıroğlu
• Çukurova Üniversitesi Tıp Fakültesi
• Farmakoloji Anabilim Dalı Adana,Turkey
• e-mail: [e-mail]