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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Review Article

Stem Cell-based Therapeutic and Diagnostic Approaches in Alzheimer's Disease

Author(s): Sadaf Abdi, Nima Javanmehr, Maryam Ghasemi-Kasman*, Hanie Yavarpour Bali and Marzieh Pirzadeh

Volume 20, Issue 6, 2022

Published on: 07 April, 2022

Page: [1093 - 1115] Pages: 23

DOI: 10.2174/1570159X20666211231090659

Price: $65

Abstract

Background: Alzheimer's disease (AD) is a neurodegenerative impairment mainly recognized by memory loss and cognitive deficits. However, the current therapies against AD are mostly limited to palliative medications, prompting researchers to investigate more efficient therapeutic approaches for AD, such as stem cell therapy. Recent evidence has proposed that extensive neuronal and synaptic loss and altered adult neurogenesis, which is perceived pivotal in terms of plasticity and network maintenance, occurs early in the course of AD, which exacerbates neuronal vulnerability to AD. Thus, regeneration and replenishing the depleted neuronal networks by strengthening the endogenous repair mechanisms or exogenous stem cells and their cargoes is a rational therapeutic approach. Currently, several stem cell-based therapies as well as stem cell products like exosomes, have shown promising results in the early diagnosis of AD.

Objective: This review begins with a comparison between AD and normal aging pathophysiology and a discussion on open questions in the field. Next, summarizing the current stem cell-based therapeutic and diagnostic approaches, we declare the advantages and disadvantages of each method. Also, we comprehensively evaluate the human clinical trials of stem cell therapies for AD.

Methodology: Peer-reviewed reports were extracted through Embase, PubMed, and Google Scholar until 2021.

Results: With several ongoing clinical trials, stem cells and their derivatives (e.g., exosomes) are an emerging and encouraging field in diagnosing and treating neurodegenerative diseases. Although stem cell therapies have been successful in animal models, numerous clinical trials in AD patients have yielded unpromising results, which we will further discuss.

Keywords: Neurodegenerative diseases, Alzheimer's disease, aging, stem cell therapy, exosomes, clinical trial.

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[1]
Liu, X-Y.; Yang, L-P.; Zhao, L. Stem cell therapy for Alzheimer’s disease. World J. Stem Cells, 2020, 12(8), 787-802.
[http://dx.doi.org/10.4252/wjsc.v12.i8.787] [PMID: 32952859]
[2]
Mayeux, R.; Stern, Y. Epidemiology of Alzheimer disease. Cold Spring Harb. Perspect. Med., 2012, 2(8)a006239
[http://dx.doi.org/10.1101/cshperspect.a006239] [PMID: 22908189]
[3]
Duncan, T.; Valenzuela, M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res. Ther., 2017, 8(1), 111.
[http://dx.doi.org/10.1186/s13287-017-0567-5] [PMID: 28494803]
[4]
Oxford, A.E.; Stewart, E.S.; Rohn, T.T. Clinical trials in Alzheimer’s disease: A hurdle in the path of remedy. Int. J. Alzheimers Dis., 2020, 20205380346
[5]
Dubois, B.; Feldman, H.H.; Jacova, C.; Dekosky, S.T.; Barberger-Gateau, P.; Cummings, J.; Delacourte, A.; Galasko, D.; Gauthier, S.; Jicha, G.; Meguro, K.; O’brien, J.; Pasquier, F.; Robert, P.; Rossor, M.; Salloway, S.; Stern, Y.; Visser, P.J.; Scheltens, P. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. Lancet Neurol., 2007, 6(8), 734-746.
[http://dx.doi.org/10.1016/S1474-4422(07)70178-3] [PMID: 17616482]
[6]
Sharpless, N.E.; DePinho, R.A. How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol., 2007, 8(9), 703-713.
[http://dx.doi.org/10.1038/nrm2241] [PMID: 17717515]
[7]
Zhang, F-Q.; Jiang, J-L.; Zhang, J-T.; Niu, H.; Fu, X-Q.; Zeng, L-L. Current status and future prospects of stem cell therapy in Alzheimer’s disease. Neural Regen. Res., 2020, 15(2), 242-250.
[http://dx.doi.org/10.4103/1673-5374.265544] [PMID: 31552889]
[8]
Lakshmi, S.; Essa, M.M.; Hartman, R.E.; Guillemin, G.J.; Sivan, S.; Elumalai, P. Exosomes in Alzheimer’s disease: potential role as pathological mediators, biomarkers and therapeutic targets. Neurochem. Res., 2020, 45(11), 2553-2559.
[http://dx.doi.org/10.1007/s11064-020-03111-1] [PMID: 32840760]
[9]
Baglio, S.R.; Pegtel, D.M.; Baldini, N. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front. Physiol., 2012, 3, 359.
[http://dx.doi.org/10.3389/fphys.2012.00359] [PMID: 22973239]
[10]
Yuyama, K.; Sun, H.; Sakai, S.; Mitsutake, S.; Okada, M.; Tahara, H.; Furukawa, J.; Fujitani, N.; Shinohara, Y.; Igarashi, Y. Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J. Biol. Chem., 2014, 289(35), 24488-24498.
[http://dx.doi.org/10.1074/jbc.M114.577213] [PMID: 25037226]
[11]
Reza-Zaldivar, E.E.; Hernández-Sapiéns, M.A.; Gutiérrez-Mercado, Y.K.; Sandoval-Ávila, S.; Gomez-Pinedo, U.; Márquez-Aguirre, A.L.; Vázquez-Méndez, E.; Padilla-Camberos, E.; Canales-Aguirre, A.A. Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease. Neural Regen. Res., 2019, 14(9), 1626-1634.
[http://dx.doi.org/10.4103/1673-5374.255978] [PMID: 31089063]
[12]
Waldau, B.; Shetty, A.K. Behavior of neural stem cells in the Alzheimer brain. Cell. Mol. Life Sci., 2008, 65(15), 2372-2384.
[http://dx.doi.org/10.1007/s00018-008-8053-y] [PMID: 18500448]
[13]
Tobin, M.K.; Musaraca, K.; Disouky, A.; Shetti, A.; Bheri, A.; Honer, W.G. Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell, 2019, 24(6), 974-982.
[http://dx.doi.org/10.1016/j.stem.2019.05.003]
[14]
Limke, T.L.; Rao, M.S. Neural stem cells in aging and disease. J. Cell. Mol. Med., 2002, 6(4), 475-496.
[http://dx.doi.org/10.1111/j.1582-4934.2002.tb00451.x] [PMID: 12611637]
[15]
Rieck, J.R.; Baracchini, G.; Nichol, D.; Abdi, H.; Grady, C.L. Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan. Neurobiol. Aging, 2021, 106, 80-94.
[http://dx.doi.org/10.1016/j.neurobiolaging.2021.03.019] [PMID: 34256190]
[16]
Albertson, A.J.; Landsness, E.C.; Tang, M.J.; Yan, P.; Miao, H.; Rosenthal, Z.P. Normal aging in mice is associated with a global reduction in cortical spectral power and a network-specific decline in functional connectivity. bioRxiv, 2021.
[17]
Dickson, D.W.; Crystal, H.A.; Mattiace, L.A.; Masur, D.M.; Blau, A.D.; Davies, P.; Yen, S.H.; Aronson, M.K. Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol. Aging, 1992, 13(1), 179-189.
[http://dx.doi.org/10.1016/0197-4580(92)90027-U] [PMID: 1311804]
[18]
Hanseeuw, B.J.; Betensky, R.A.; Jacobs, H.I.L.; Schultz, A.P.; Sepulcre, J.; Becker, J.A.; Cosio, D.M.O.; Farrell, M.; Quiroz, Y.T.; Mormino, E.C.; Buckley, R.F.; Papp, K.V.; Amariglio, R.A.; Dewachter, I.; Ivanoiu, A.; Huijbers, W.; Hedden, T.; Marshall, G.A.; Chhatwal, J.P.; Rentz, D.M.; Sperling, R.A.; Johnson, K. Association of amyloid and Tau with cognition in Preclinical Alzheimer Disease: A Longitudinal Study. JAMA Neurol., 2019, 76(8), 915-924.
[http://dx.doi.org/10.1001/jamaneurol.2019.1424] [PMID: 31157827]
[19]
Feng, X.; Guo, J.; Sigmon, H.C.; Sloan, R.P.; Brickman, A.M.; Provenzano, F.A.; Small, S.A. Brain regions vulnerable and resistant to aging without Alzheimer’s disease. PLoS One, 2020, 15(7)e0234255
[http://dx.doi.org/10.1371/journal.pone.0234255] [PMID: 32726311]
[20]
Tincer, G.; Mashkaryan, V.; Bhattarai, P.; Kizil, C. Neural stem/progenitor cells in Alzheimer’s disease. Yale J. Biol. Med., 2016, 89(1), 23-35.
[PMID: 27505014]
[21]
Xia, X.; Jiang, Q.; McDermott, J.; Han, J.J. Aging and Alzheimer’s disease: Comparison and associations from molecular to system level. Aging Cell, 2018, 17(5)e12802
[http://dx.doi.org/10.1111/acel.12802] [PMID: 29963744]
[22]
Lin, J.; Wang, Y.; Wei, X.; Kong, S.; Liu, Z.; Liu, J.; Zhang, F.; Lin, S.; Ji, B.; Zhou, Z.; Guo, Z. Controllable antibacterial and bacterially anti-adhesive surface fabricated by a bio-inspired beetle-like macromolecule. Int. J. Biol. Macromol., 2020, 157, 553-560.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.04.207] [PMID: 32353498]
[23]
Mosher, K.I.; Wyss-Coray, T. Microglial dysfunction in brain aging and Alzheimer’s disease. Biochem. Pharmacol., 2014, 88(4), 594-604.
[http://dx.doi.org/10.1016/j.bcp.2014.01.008] [PMID: 24445162]
[24]
Rodríguez-Arellano, J.J.; Parpura, V.; Zorec, R.; Verkhratsky, A. Astrocytes in physiological aging and Alzheimer’s disease. Neuroscience, 2016, 323, 170-182.
[http://dx.doi.org/10.1016/j.neuroscience.2015.01.007] [PMID: 25595973]
[25]
Zhang, P.; Kishimoto, Y.; Grammatikakis, I.; Gottimukkala, K.; Cutler, R.G.; Zhang, S.; Abdelmohsen, K.; Bohr, V.A.; Misra Sen, J.; Gorospe, M.; Mattson, M.P. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model. Nat. Neurosci., 2019, 22(5), 719-728.
[http://dx.doi.org/10.1038/s41593-019-0372-9] [PMID: 30936558]
[26]
Deng, Y.; Zhang, T.; Sharma, B.K.; Nie, H. Optimization and mechanism studies on cell disruption and phosphorus recovery from microalgae with magnesium modified hydrochar in assisted hydrothermal system. Sci. Total Environ., 2019, 646, 1140-1154.
[http://dx.doi.org/10.1016/j.scitotenv.2018.07.369] [PMID: 30235600]
[27]
Oh, S.H.; Kim, H.N.; Park, H-J.; Shin, J.Y.; Lee, P.H. Mesenchymal stem cells increase hippocampal neurogenesis and neuronal differentiation by enhancing the Wnt signaling pathway in an Alzheimer’s disease model. Cell Transplant., 2015, 24(6), 1097-1109.
[http://dx.doi.org/10.3727/096368914X679237] [PMID: 24612635]
[28]
Zhao, C.; Deng, W.; Gage, F.H. Mechanisms and functional implications of adult neurogenesis. Cell, 2008, 132(4), 645-660.
[http://dx.doi.org/10.1016/j.cell.2008.01.033] [PMID: 18295581]
[29]
Gao, Z.; Ure, K.; Ables, J.L.; Lagace, D.C.; Nave, K-A.; Goebbels, S.; Eisch, A.J.; Hsieh, J. Neurod1 is essential for the survival and maturation of adult-born neurons. Nat. Neurosci., 2009, 12(9), 1090-1092.
[http://dx.doi.org/10.1038/nn.2385] [PMID: 19701197]
[30]
Paredes, M.F.; James, D.; Gil-Perotin, S.; Kim, H.; Cotter, J.A.; Ng, C.; Sandoval, K.; Rowitch, D.H.; Xu, D.; McQuillen, P.S.; Garcia-Verdugo, J.M.; Huang, E.J.; Alvarez-Buylla, A. Extensive migration of young neurons into the infant human frontal lobe. Science, 2016, 354(6308), 354.
[http://dx.doi.org/10.1126/science.aaf7073] [PMID: 27846470]
[31]
Jurkowski, M.P.; Bettio, L. Beyond the hippocampus and the SVZ: adult neurogenesis throughout the brain. Front. Cell. Neurosci., 2020, 14, 293.
[http://dx.doi.org/10.3389/fncel.2020.576444]
[32]
Ohira, K. Regulation of adult neurogenesis in the cerebral cortex. J. Neurol. Neuromed., 2018, 3(4)
[http://dx.doi.org/10.29245/2572.942X/2018/4.1192]
[33]
Aimone, J.B.; Li, Y.; Lee, S.W.; Clemenson, G.D.; Deng, W.; Gage, F.H. Regulation and function of adult neurogenesis: from genes to cognition. Physiol. Rev., 2014, 94(4), 991-1026.
[http://dx.doi.org/10.1152/physrev.00004.2014] [PMID: 25287858]
[34]
Denoth-Lippuner, A.; Jessberger, S. Formation and integration of new neurons in the adult hippocampus. Nat. Rev. Neurosci., 2021, 22(4), 223-236.
[http://dx.doi.org/10.1038/s41583-021-00433-z] [PMID: 33633402]
[35]
Faghihi, F.; Moustafa, A.A. Impaired neurogenesis of the dentate gyrus is associated with pattern separation deficits: A computational study. J. Integr. Neurosci., 2016, 15(3), 277-293.
[http://dx.doi.org/10.1142/S0219635216500175] [PMID: 27650784]
[36]
Wiskott, L.; Rasch, M.J.; Kempermann, G. A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus. Hippocampus, 2006, 16(3), 329-343.
[http://dx.doi.org/10.1002/hipo.20167] [PMID: 16435309]
[37]
Sawada, M.; Matsumoto, M.; Sawamoto, K. Vascular regulation of adult neurogenesis under physiological and pathological conditions. Front. Neurosci., 2014, 8, 53.
[http://dx.doi.org/10.3389/fnins.2014.00053] [PMID: 24672424]
[38]
Jung, S.; Choe, S.; Woo, H.; Jeong, H.; An, H-K.; Moon, H.; Ryu, H.Y.; Yeo, B.K.; Lee, Y.W.; Choi, H.; Mun, J.Y.; Sun, W.; Choe, H.K.; Kim, E.K.; Yu, S.W. Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits. Autophagy, 2020, 16(3), 512-530.
[http://dx.doi.org/10.1080/15548627.2019.1630222] [PMID: 31234698]
[39]
Bishop, N.A.; Lu, T.; Yankner, B.A. Neural mechanisms of ageing and cognitive decline. Nature, 2010, 464(7288), 529-535.
[http://dx.doi.org/10.1038/nature08983] [PMID: 20336135]
[40]
Raber, J.; Rola, R.; LeFevour, A.; Morhardt, D.; Curley, J.; Mizumatsu, S.; VandenBerg, S.R.; Fike, J.R. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat. Res., 2004, 162(1), 39-47.
[http://dx.doi.org/10.1667/RR3206] [PMID: 15222778]
[41]
Ma, D.K.; Marchetto, M.C.; Guo, J.U.; Ming, G.L.; Gage, F.H.; Song, H. Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat. Neurosci., 2010, 13(11), 1338-1344.
[http://dx.doi.org/10.1038/nn.2672] [PMID: 20975758]
[42]
Malberg, J.E.; Hen, R.; Madsen, T.M. Adult neurogenesis and antidepressant treatment; the surprise finding by Ron Duman and the field 20 years later. Biol. Psychiatry, 2021, 90(2), 96-101.
[http://dx.doi.org/10.1016/j.biopsych.2021.01.010] [PMID: 33771348]
[43]
Fujioka, T.; Kaneko, N.; Ajioka, I.; Nakaguchi, K.; Omata, T.; Ohba, H.; Fässler, R.; García-Verdugo, J.M.; Sekiguchi, K.; Matsukawa, N.; Sawamoto, K. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain. EBioMedicine, 2017, 16, 195-203.
[http://dx.doi.org/10.1016/j.ebiom.2017.01.005] [PMID: 28153772]
[44]
Kaneko, N.; Herranz-Pérez, V.; Otsuka, T.; Sano, H.; Ohno, N.; Omata, T.; Nguyen, H.B.; Thai, T.Q.; Nambu, A.; Kawaguchi, Y.; García-Verdugo, J.M.; Sawamoto, K. New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration. Sci. Adv., 2018, 4(12)eaav0618
[http://dx.doi.org/10.1126/sciadv.aav0618] [PMID: 30547091]
[45]
Jinnou, H.; Sawada, M.; Kawase, K.; Kaneko, N.; Herranz-Pérez, V.; Miyamoto, T. Radial glial fibers promote neuronal migration and functional recovery after neonatal brain injury. Cell Stem Cell, 2018, 22(1), 128-137.
[http://dx.doi.org/10.1016/j.stem.2017.11.005]
[46]
Kim, T.A.; Chen, L.; Ge, S. The interplay of neurovasculature and adult hippocampal neurogenesis. Neurosci. Lett., 2021, 760136071
[http://dx.doi.org/10.1016/j.neulet.2021.136071] [PMID: 34147540]
[47]
Futtrup, J.; Margolinsky, R.; Benros, M.E.; Moos, T.; Routhe, L.J.; Rungby, J. Blood-brain barrier pathology in patients with severe mental disorders: A systematic review and meta-analysis of biomarkers in case-control studies. Brain Behav. Immun-Health, 2020, 6100102
[http://dx.doi.org/10.1016/j.bbih.2020.100102]
[48]
Gemma, C.; Bachstetter, A.D. The role of microglia in adult hippocampal neurogenesis. Front. Cell. Neurosci., 2013, 7, 229.
[http://dx.doi.org/10.3389/fncel.2013.00229] [PMID: 24319411]
[49]
Morton, M.C.; Neckles, V.N.; Seluzicki, C.M.; Holmberg, J.C.; Feliciano, D.M. Neonatal subventricular zone neural stem cells release extracellular vesicles that act as a microglial morphogen. Cell Rep., 2018, 23(1), 78-89.
[http://dx.doi.org/10.1016/j.celrep.2018.03.037] [PMID: 29617675]
[50]
Peruzzotti-Jametti, L.; Bernstock, J.D.; Vicario, N.; Costa, A.S.; Kwok, C.K.; Leonardi, T. Macrophage-derived extracellular succinate licenses neural stem cells to suppress chronic neuroinflammation. Cell Stem Cell, 2018, 22(3), 355-368.
[http://dx.doi.org/10.1016/j.stem.2018.01.020]
[51]
Palmer, T.D.; Markakis, E.A.; Willhoite, A.R.; Safar, F.; Gage, F.H. Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J. Neurosci., 1999, 19(19), 8487-8497.
[http://dx.doi.org/10.1523/JNEUROSCI.19-19-08487.1999] [PMID: 10493749]
[52]
Seidenfaden, R.; Desoeuvre, A.; Bosio, A.; Virard, I.; Cremer, H. Glial conversion of SVZ-derived committed neuronal precursors after ectopic grafting into the adult brain. Mol. Cell. Neurosci., 2006, 32(1-2), 187-198.
[http://dx.doi.org/10.1016/j.mcn.2006.04.003] [PMID: 16730456]
[53]
Wang, Z-L.; Cheng, S-M.; Ma, M-M.; Ma, Y-P.; Yang, J-P.; Xu, G-L.; Liu, X.F. Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia. Neurosci. Lett., 2008, 446(1), 30-35.
[http://dx.doi.org/10.1016/j.neulet.2008.09.030] [PMID: 18822350]
[54]
Fujiwara, N.; Shimizu, J.; Takai, K.; Arimitsu, N.; Saito, A.; Kono, T.; Umehara, T.; Ueda, Y.; Wakisaka, S.; Suzuki, T.; Suzuki, N. Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells. Neurosci. Lett., 2013, 557(Pt B), 129-134.
[http://dx.doi.org/10.1016/j.neulet.2013.10.043] [PMID: 24466594]
[55]
Jiang, D.; Chen, F-X.; Zhou, H.; Lu, Y-Y.; Tan, H.; Yu, S-J.; Yuan, J.; Liu, H.; Meng, W.; Jin, Z.B. Bioenergetic crosstalk between mesenchymal stem cells and various ocular cells through the intercellular trafficking of mitochondria. Theranostics, 2020, 10(16), 7260-7272.
[http://dx.doi.org/10.7150/thno.46332] [PMID: 32641991]
[56]
Ng, T.K.S.; Ho, C.S.H.; Tam, W.W.S.; Kua, E.H.; Ho, R.C-M. Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): A systematic review and meta-analysis. Int. J. Mol. Sci., 2019, 20(2), 257.
[http://dx.doi.org/10.3390/ijms20020257] [PMID: 30634650]
[57]
Pan, D.; Xia, X-X.; Zhou, H.; Jin, S-Q.; Lu, Y-Y.; Liu, H.; Gao, M.L.; Jin, Z.B. COCO enhances the efficiency of photoreceptor precursor differentiation in early human embryonic stem cell-derived retinal organoids. Stem Cell Res. Ther., 2020, 11(1), 366.
[http://dx.doi.org/10.1186/s13287-020-01883-5] [PMID: 32831148]
[58]
Fleifel, D.; Rahmoon, M.A.; AlOkda, A.; Nasr, M.; Elserafy, M.; El-Khamisy, S.F. Recent advances in stem cells therapy: A focus on cancer. Parkinson’s and Alzheimer’s. J. Genet. Eng. Biotechnol., 2018, 16(2), 427-432.
[http://dx.doi.org/10.1016/j.jgeb.2018.09.002] [PMID: 30733756]
[59]
Choi, S.H.; Bylykbashi, E.; Chatila, Z.K.; Lee, S.W.; Pulli, B.; Clemenson, G.D.; Kim, E.; Rompala, A.; Oram, M.K.; Asselin, C.; Aronson, J.; Zhang, C.; Miller, S.J.; Lesinski, A.; Chen, J.W.; Kim, D.Y.; van Praag, H.; Spiegelman, B.M.; Gage, F.H.; Tanzi, R.E. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science, 2018, 361(6406)eaan8821
[http://dx.doi.org/10.1126/science.aan8821] [PMID: 30190379]
[60]
Moreno-Jiménez, E.P.; Flor-García, M.; Terreros-Roncal, J.; Rábano, A.; Cafini, F.; Pallas-Bazarra, N.; Ávila, J.; Llorens-Martín, M. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat. Med., 2019, 25(4), 554-560.
[http://dx.doi.org/10.1038/s41591-019-0375-9] [PMID: 30911133]
[61]
Savukinas, U.B.; Enes, S.R.; Sjöland, A.A.; Westergren-Thorsson, G. Concise review: The bystander effect: mesenchymal stem cell-mediated lung repair. Stem Cells, 2016, 34(6), 1437-1444.
[http://dx.doi.org/10.1002/stem.2357] [PMID: 26991735]
[62]
Wang, S-M.; Lee, C-U.; Lim, H.K. Stem cell therapies for Alzheimer’s disease: is it time? Curr. Opin. Psychiatry, 2019, 32(2), 105-116.
[http://dx.doi.org/10.1097/YCO.0000000000000478] [PMID: 30557266]
[63]
Zhang, J.; Liu, B. A review on the recent developments of sequence-based protein feature extraction methods. Curr. Bioinform., 2019, 14(3), 190-199.
[http://dx.doi.org/10.2174/1574893614666181212102749]
[64]
Lanza, R.; Atala, A. Essentials of Stem Cell Biology, 3rd ed; , 2013, pp. 1-713.
[65]
Hamilton, L.K.; Dufresne, M.; Joppé, S.E.; Petryszyn, S.; Aumont, A.; Calon, F.; Barnabé-Heider, F.; Furtos, A.; Parent, M.; Chaurand, P.; Fernandes, K.J. Aberrant lipid metabolism in the forebrain niche suppresses adult neural stem cell proliferation in an animal model of Alzheimer’s disease. Cell Stem Cell, 2015, 17(4), 397-411.
[http://dx.doi.org/10.1016/j.stem.2015.08.001] [PMID: 26321199]
[66]
Tang, Y.; Yu, P.; Cheng, L. Current progress in the derivation and therapeutic application of neural stem cells., 2017.
[67]
Dever, D.P.; Scharenberg, S.G.; Camarena, J.; Kildebeck, E.J.; Clark, J.T.; Martin, R.M.; Bak, R.O.; Tang, Y.; Dohse, M.; Birgmeier, J.A.; Jagadeesh, K.A.; Bejerano, G.; Tsukamoto, A.; Gomez-Ospina, N.; Uchida, N.; Porteus, M.H. CRISPR/Cas9 genome engineering in engraftable human brain-derived neural stem cells. iScience, 2019, 15, 524-535.
[http://dx.doi.org/10.1016/j.isci.2019.04.036] [PMID: 31132746]
[68]
Pötzsch, A.; Zocher, S.; Bernas, S.N.; Leiter, O.; Rünker, A.E.; Kempermann, G. L-lactate exerts a pro-proliferative effect on adult hippocampal precursor cells in vitro. iScience, 2021, 24(2), 102126.
[http://dx.doi.org/10.1016/j.isci.2021.102126] [PMID: 33659884]
[69]
Hattiangady, B.; Kuruba, R.; Shuai, B.; Grier, R.; Shetty, A.K. Hippocampal neural stem cell grafting after status epilepticus alleviates chronic epilepsy and abnormal plasticity, and maintains better memory and mood function. Aging Dis., 2020, 11(6), 1374-1394.
[http://dx.doi.org/10.14336/AD.2020.1020] [PMID: 33269095]
[70]
Tan, B.; Luo, Z.; Yue, Y.; Liu, Y.; Pan, L.; Yu, L. Effects of FTY720 (fingolimod) on proliferation, differentiation, and migration of brain-derived neural stem cells. Stem Cells Int., 2016, 20169671732
[71]
Xu, X.; Warrington, A.E.; Bieber, A.J.; Rodriguez, M. Enhancing CNS repair in neurological disease: challenges arising from neurodegeneration and rewiring of the network. CNS Drugs, 2011, 25(7), 555-573.
[http://dx.doi.org/10.2165/11587830-000000000-00000] [PMID: 21699269]
[72]
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126(4), 663-676.
[73]
Caprnda, M.; Kubatka, P.; Gazdikova, K.; Gasparova, I.; Valentova, V.; Stollarova, N.; La Rocca, G.; Kobyliak, N.; Dragasek, J.; Mozos, I.; Prosecky, R.; Siniscalco, D.; Büsselberg, D.; Rodrigo, L.; Kruzliak, P. Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative disorders. Biomed. Pharmacother., 2017, 91, 60-69.
[http://dx.doi.org/10.1016/j.biopha.2017.04.034] [PMID: 28448871]
[74]
Sivandzade, F.; Cucullo, L. Regenerative stem cell therapy for neurodegenerative diseases: An overview. Int. J. Mol. Sci., 2021, 22(4), 2153.
[http://dx.doi.org/10.3390/ijms22042153] [PMID: 33671500]
[75]
Schweitzer, J.S.; Song, B.; Herrington, T.M.; Park, T-Y.; Lee, N.; Ko, S.; Jeon, J.; Cha, Y.; Kim, K.; Li, Q.; Henchcliffe, C.; Kaplitt, M.; Neff, C.; Rapalino, O.; Seo, H.; Lee, I.H.; Kim, J.; Kim, T.; Petsko, G.A.; Ritz, J.; Cohen, B.M.; Kong, S.W.; Leblanc, P.; Carter, B.S.; Kim, K.S. Personalized iPSC-derived dopamine progenitor cells for Parkinson’s disease. N. Engl. J. Med., 2020, 382(20), 1926-1932.
[http://dx.doi.org/10.1056/NEJMoa1915872] [PMID: 32402162]
[76]
Ahani-Nahayati, M.; Shariati, A.; Mahmoodi, M.; Olegovna Zekiy, A.; Javidi, K.; Shamlou, S.; Mousakhani, A.; Zamani, M.; Hassanzadeh, A. Stem cell in neurodegenerative disorders; an emerging strategy. Int. J. Dev. Neurosci., 2021, 81(4), 291-311.
[http://dx.doi.org/10.1002/jdn.10101] [PMID: 33650716]
[77]
Waller, M.; Neely, G.G.; Caron, L.
[78]
Yue, W.; Li, Y.; Zhang, T.; Jiang, M.; Qian, Y.; Zhang, M.; Sheng, N.; Feng, S.; Tang, K.; Yu, X.; Shu, Y.; Yue, C.; Jing, N. ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer’s disease in mouse models. Stem Cell Reports, 2015, 5(5), 776-790.
[http://dx.doi.org/10.1016/j.stemcr.2015.09.010] [PMID: 26489896]
[79]
Kolagar, T.A.; Farzaneh, M.; Nikkar, N.; Khoshnam, S.E. Human pluripotent stem cells in neurodegenerative diseases: potentials, advances and limitations. Curr. Stem Cell Res. Ther., 2020, 15(2), 102-110.
[http://dx.doi.org/10.2174/1574888X14666190823142911] [PMID: 31441732]
[80]
Mandai, M.; Watanabe, A.; Kurimoto, Y.; Hirami, Y.; Morinaga, C.; Daimon, T.; Fujihara, M.; Akimaru, H.; Sakai, N.; Shibata, Y.; Terada, M.; Nomiya, Y.; Tanishima, S.; Nakamura, M.; Kamao, H.; Sugita, S.; Onishi, A.; Ito, T.; Fujita, K.; Kawamata, S.; Go, M.J.; Shinohara, C.; Hata, K.I.; Sawada, M.; Yamamoto, M.; Ohta, S.; Ohara, Y.; Yoshida, K.; Kuwahara, J.; Kitano, Y.; Amano, N.; Umekage, M.; Kitaoka, F.; Tanaka, A.; Okada, C.; Takasu, N.; Ogawa, S.; Yamanaka, S.; Takahashi, M. Autologous induced stem-cell–derived retinal cells for macular degeneration. N. Engl. J. Med., 2017, 376(11), 1038-1046.
[http://dx.doi.org/10.1056/NEJMoa1608368] [PMID: 28296613]
[81]
Lim, L.S.; Mitchell, P.; Seddon, J.M.; Holz, F.G.; Wong, T.Y. Age-related macular degeneration. Lancet, 2012, 379(9827), 1728-1738.
[http://dx.doi.org/10.1016/S0140-6736(12)60282-7] [PMID: 22559899]
[82]
Mareschi, K.; Novara, M.; Rustichelli, D.; Ferrero, I.; Guido, D.; Carbone, E.; Medico, E.; Madon, E.; Vercelli, A.; Fagioli, F. Neural differentiation of human mesenchymal stem cells: Evidence for expression of neural markers and eag K+ channel types. Exp. Hematol., 2006, 34(11), 1563-1572.
[http://dx.doi.org/10.1016/j.exphem.2006.06.020] [PMID: 17046576]
[83]
Zanini, C.; Bruno, S.; Mandili, G.; Baci, D.; Cerutti, F.; Cenacchi, G.; Izzi, L.; Camussi, G.; Forni, M. Differentiation of mesenchymal stem cells derived from pancreatic islets and bone marrow into islet-like cell phenotype. PLoS One, 2011, 6(12)e28175
[http://dx.doi.org/10.1371/journal.pone.0028175] [PMID: 22194812]
[84]
Boyton, S.; Clemenson, L. Mesenchymal stem cells: sources, clinical applications and outcomes for common musculoskeletal conditions. Clinical Practice in Athletic Training., 2020, 3(1), 4-5.
[http://dx.doi.org/10.31622/2020/0003.2]
[85]
Liu, J.; Yu, F.; Sun, Y.; Jiang, B.; Zhang, W.; Yang, J.; Xu, G.T.; Liang, A.; Liu, S. Concise reviews: Characteristics and potential applications of human dental tissue-derived mesenchymal stem cells. Stem Cells, 2015, 33(3), 627-638.
[http://dx.doi.org/10.1002/stem.1909] [PMID: 25447379]
[86]
Sadatpoor, S.O.; Salehi, Z.; Rahban, D.; Salimi, A. Manipulated mesenchymal stem cells applications in neurodegenerative diseases. Int. J. Stem Cells, 2020, 13(1), 24-45.
[http://dx.doi.org/10.15283/ijsc19031] [PMID: 32114741]
[87]
Hawkins, K.E.; Corcelli, M.; Dowding, K.; Ranzoni, A.M.; Vlahova, F.; Hau, K.L.; Hunjan, A.; Peebles, D.; Gressens, P.; Hagberg, H.; de Coppi, P.; Hristova, M.; Guillot, P.V. Embryonic stem cell‐derived mesenchymal stem cells (MSCs) have a superior neuroprotective capacity over fetal MSCs in the hypoxic‐ischemic mouse brain. Stem Cells Transl. Med., 2018, 7(5), 439-449.
[http://dx.doi.org/10.1002/sctm.17-0260] [PMID: 29489062]
[88]
Ra, J.C.; Shin, I.S.; Kim, S.H.; Kang, S.K.; Kang, B.C.; Lee, H.Y.; Kim, Y.J.; Jo, J.Y.; Yoon, E.J.; Choi, H.J.; Kwon, E. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev., 2011, 20(8), 1297-1308.
[http://dx.doi.org/10.1089/scd.2010.0466] [PMID: 21303266]
[89]
Hosseini, S.A.; Mohammadi, R.; Noruzi, S.; Mohamadi, Y.; Azizian, M.; Mousavy, S.M.; Ghasemi, F.; Hesari, A.; Sahebkar, A.; Salarinia, R.; Aghdam, A.M.; Mirzaei, H. Stem cell- and gene-based therapies as potential candidates in Alzheimer’s therapy. J. Cell. Biochem., 2018, 119(11), 8723-8736.
[http://dx.doi.org/10.1002/jcb.27202] [PMID: 30074262]
[90]
Song, N.; Scholtemeijer, M.; Shah, K. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol. Sci., 2020, 41(9), 653-664.
[http://dx.doi.org/10.1016/j.tips.2020.06.009] [PMID: 32709406]
[91]
Teixeira, F.G.; Salgado, A.J. Mesenchymal stem cells secretome: current trends and future challenges. Neural Regen. Res., 2020, 15(1), 75-77.
[http://dx.doi.org/10.4103/1673-5374.264455] [PMID: 31535654]
[92]
Xu, L.; Jiang, S.; Zou, Q An insilico approach to identification, categorization and prediction of nucleic acid binding proteins. Bio Rxiv, 2020, 22(3), bbaa171.
[http://dx.doi.org/10.1101/2020.05.05.078741]
[93]
Nakano, M.; Kubota, K.; Kobayashi, E.; Chikenji, T.S.; Saito, Y.; Konari, N.; Fujimiya, M. Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an Alzheimer’s disease model by increasing the expression of microRNA-146a in hippocampus. Sci. Rep., 2020, 10(1), 10772.
[http://dx.doi.org/10.1038/s41598-020-67460-1] [PMID: 32612165]
[94]
Weiss, A.R.R.; Dahlke, M.H. Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front. Immunol., 2019, 10, 1191.
[http://dx.doi.org/10.3389/fimmu.2019.01191] [PMID: 31214172]
[95]
Kim, J.; Lee, Y.; Lee, S.; Kim, K.; Song, M.; Lee, J. Mesenchymal stem cell therapy and Alzheimer’s disease: Current status and future perspectives. J. Alzheimers Dis., 2020, 1-14.
[http://dx.doi.org/10.3233/JAD-200219]
[96]
Wang, X-F.; Gao, P.; Liu, Y-F.; Li, H-F.; Lu, F. Predicting thermophilic proteins by machine learning. Curr. Bioinform., 2020, 15(5), 493-502.
[http://dx.doi.org/10.2174/1574893615666200207094357]
[97]
Ahmed, L.A.; Al-Massri, K.F. Directions for enhancement of the therapeutic efficacy of mesenchymal stem cells in different neurodegenerative and cardiovascular diseases: current status and future perspectives. Curr. Stem Cell Res. Ther., 2021, 16(7), 858-876.
[http://dx.doi.org/10.2174/1574888X16666210303151237] [PMID: 33655876]
[98]
Kim, D.H.; Lee, D.; Chang, E.H.; Kim, J.H.; Hwang, J.W.; Kim, J-Y.; Kyung, J.W.; Kim, S.H.; Oh, J.S.; Shim, S.M.; Na, D.L.; Oh, W.; Chang, J.W. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer’s disease model. Stem Cells Dev., 2015, 24(20), 2378-2390.
[http://dx.doi.org/10.1089/scd.2014.0487] [PMID: 26154268]
[99]
Zomer, H.D.; Vidane, A.S.; Gonçalves, N.N.; Ambrósio, C.E. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives. Stem Cells Cloning, 2015, 8, 125-134.
[PMID: 26451119]
[100]
Hu, L.; Hu, J.; Zhao, J.; Liu, J.; Ouyang, W.; Yang, C. Side-by-side comparison of the biological characteristics of human umbilical cord and adipose tissue-derived mesenchymal stem cells. BioMed Res. Int., 2013, 2013438243
[http://dx.doi.org/10.1155/2013/438243]
[101]
Kabat, M.; Bobkov, I.; Kumar, S.; Grumet, M. Trends in mesenchymal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range? Stem Cells Transl. Med., 2020, 9(1), 17-27.
[http://dx.doi.org/10.1002/sctm.19-0202] [PMID: 31804767]
[102]
Mielke, M.M. Sex and gender differences in Alzheimer’s disease dementia. Psychiatr. Times, 2018, 35(11), 14-17.
[PMID: 30820070]
[103]
Zou, Q.; Xing, P.; Wei, L.; Liu, B. Gene2vec: gene subsequence embedding for prediction of mammalian N6-methyladenosine sites from mRNA. RNA, 2019, 25(2), 205-218.
[http://dx.doi.org/10.1261/rna.069112.118] [PMID: 30425123]
[104]
Li, X.; Hou, W.; Wu, X.; Jiang, W.; Chen, H.; Xiao, N.; Zhou, P. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment. Neural Regen. Res., 2014, 9(3), 236-242.
[http://dx.doi.org/10.4103/1673-5374.128214] [PMID: 25206807]
[105]
Volarevic, V.; Markovic, B.S.; Gazdic, M.; Volarevic, A.; Jovicic, N.; Arsenijevic, N.; Armstrong, L.; Djonov, V.; Lako, M.; Stojkovic, M. Ethical and safety issues of stem cell-based therapy. Int. J. Med. Sci., 2018, 15(1), 36-45.
[http://dx.doi.org/10.7150/ijms.21666] [PMID: 29333086]
[106]
van Niel, G.; D’Angelo, G.; Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol., 2018, 19(4), 213-228.
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[107]
Jiang, Q.; Jin, S.; Jiang, Y.; Liao, M.; Feng, R.; Zhang, L.; Liu, G.; Hao, J. Alzheimer’s disease variants with the genome-wide significance are significantly enriched in immune pathways and active in immune cells. Mol. Neurobiol., 2017, 54(1), 594-600.
[http://dx.doi.org/10.1007/s12035-015-9670-8] [PMID: 26746668]
[108]
Reza-Zaldivar, E.E.; Hernández-Sapiéns, M.A.; Minjarez, B.; Gutiérrez-Mercado, Y.K.; Márquez-Aguirre, A.L.; Canales-Aguirre, A.A. Potential effects of MSC-derived exosomes in neuroplasticity in Alzheimer’s disease. Front. Cell. Neurosci., 2018, 12, 317.
[http://dx.doi.org/10.3389/fncel.2018.00317] [PMID: 30319358]
[109]
Cheng, L.; Zhang, K.; Wu, S.; Cui, M.; Xu, T. Focus on mesenchymal stem cell-derived exosomes: Opportunities and challenges in cell-free therapy. Stem Cells Int., 2017, 20176305295
[http://dx.doi.org/10.1155/2017/6305295]
[110]
Bruno, S.; Grange, C.; Collino, F.; Deregibus, M.C.; Cantaluppi, V.; Biancone, L.; Tetta, C.; Camussi, G. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS One, 2012, 7(3)e33115
[http://dx.doi.org/10.1371/journal.pone.0033115] [PMID: 22431999]
[111]
Xin, H.; Li, Y.; Buller, B.; Katakowski, M.; Zhang, Y.; Wang, X.; Shang, X.; Zhang, Z.G.; Chopp, M. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells, 2012, 30(7), 1556-1564.
[http://dx.doi.org/10.1002/stem.1129] [PMID: 22605481]
[112]
Bruno, S.; Grange, C.; Deregibus, M.C.; Calogero, R.A.; Saviozzi, S.; Collino, F.; Morando, L.; Busca, A.; Falda, M.; Bussolati, B.; Tetta, C.; Camussi, G. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J. Am. Soc. Nephrol., 2009, 20(5), 1053-1067.
[http://dx.doi.org/10.1681/ASN.2008070798] [PMID: 19389847]
[113]
Han, C.; Sun, X.; Liu, L.; Jiang, H.; Shen, Y.; Xu, X. Exosomes and their therapeutic potentials of stem cells. Stem Cells Int., 2016, 20167653489
[http://dx.doi.org/10.1155/2016/7653489]
[114]
Beach, A.; Zhang, H-G.; Ratajczak, M.Z.; Kakar, S.S. Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J. Ovarian Res., 2014, 7(1), 14.
[http://dx.doi.org/10.1186/1757-2215-7-14] [PMID: 24460816]
[115]
Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol., 2002, 2(8), 569-579.
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[116]
He, C.; Zheng, S.; Luo, Y.; Wang, B. Exosome theranostics: biology and translational medicine. Theranostics, 2018, 8(1), 237-255.
[http://dx.doi.org/10.7150/thno.21945] [PMID: 29290805]
[117]
Colombo, M.; Raposo, G.; Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol., 2014, 30, 255-289.
[http://dx.doi.org/10.1146/annurev-cellbio-101512-122326] [PMID: 25288114]
[118]
Keerthikumar, S.; Chisanga, D.; Ariyaratne, D.; Al Saffar, H.; Anand, S.; Zhao, K.; Samuel, M.; Pathan, M.; Jois, M.; Chilamkurti, N.; Gangoda, L.; Mathivanan, S. ExoCarta: a web-based compendium of exosomal cargo. J. Mol. Biol., 2016, 428(4), 688-692.
[http://dx.doi.org/10.1016/j.jmb.2015.09.019] [PMID: 26434508]
[119]
Hall, J.; Prabhakar, S.; Balaj, L.; Lai, C.P.; Cerione, R.A.; Breakefield, X.O. Delivery of therapeutic proteins via extracellular vesicles: Review and potential treatments for Parkinson’s disease, glioma, and schwannoma. Cell. Mol. Neurobiol., 2016, 36(3), 417-427.
[http://dx.doi.org/10.1007/s10571-015-0309-0] [PMID: 27017608]
[120]
Abels, E.R.; Breakefield, X.O. Introduction to extracellular vesicles: biogenesis, rna cargo selection, content, release, and uptake. Cell. Mol. Neurobiol., 2016, 36(3), 301-312.
[121]
Pang, X.; Gong, K.; Zhang, X.; Wu, S.; Cui, Y.; Qian, B-Z. Osteopontin as a multifaceted driver of bone metastasis and drug resistance. Pharmacol. Res., 2019, 144, 235-244.
[http://dx.doi.org/10.1016/j.phrs.2019.04.030] [PMID: 31028902]
[122]
Stuffers, S.; Sem Wegner, C.; Stenmark, H.; Brech, A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic, 2009, 10(7), 925-937.
[http://dx.doi.org/10.1111/j.1600-0854.2009.00920.x] [PMID: 19490536]
[123]
Juan, T.; Fürthauer, M. Biogenesis and function of ESCRT-dependent extracellular vesicles. Semin. Cell Dev. Biol., 2018, 74, 66-77.
[124]
Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478)eaau6977
[http://dx.doi.org/10.1126/science.aau6977] [PMID: 32029601]
[125]
Airola, M.V.; Hannun, Y.A. Sphingolipid metabolism and neutral sphingomyelinases. In: Sphingolipids: Basic Science and Drug Development; Springer, 2013, pp. 57-76.
[http://dx.doi.org/10.1007/978-3-7091-1368-4_3]
[126]
Lee, S.; Mankhong, S.; Kang, J-H. Extracellular vesicle as a source of Alzheimer’s biomarkers: opportunities and challenges. Int. J. Mol. Sci., 2019, 20(7), 1728.
[http://dx.doi.org/10.3390/ijms20071728] [PMID: 30965555]
[127]
Miners, J.S.; Barua, N.; Kehoe, P.G.; Gill, S.; Love, S. Aβ-degrading enzymes: potential for treatment of Alzheimer disease. J. Neuropathol. Exp. Neurol., 2011, 70(11), 944-959.
[http://dx.doi.org/10.1097/NEN.0b013e3182345e46] [PMID: 22002425]
[128]
Tamboli, I.Y.; Barth, E.; Christian, L.; Siepmann, M.; Kumar, S.; Singh, S.; Tolksdorf, K.; Heneka, M.T.; Lütjohann, D.; Wunderlich, P.; Walter, J. Statins promote the degradation of extracellular amyloid β-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion. J. Biol. Chem., 2010, 285(48), 37405-37414.
[http://dx.doi.org/10.1074/jbc.M110.149468] [PMID: 20876579]
[129]
Katsuda, T.; Tsuchiya, R.; Kosaka, N.; Yoshioka, Y.; Takagaki, K.; Oki, K.; Takeshita, F.; Sakai, Y.; Kuroda, M.; Ochiya, T. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci. Rep., 2013, 3(1), 1197.
[http://dx.doi.org/10.1038/srep01197] [PMID: 23378928]
[130]
Yaghoubi, Y.; Movassaghpour, A.; Zamani, M.; Talebi, M.; Mehdizadeh, A.; Yousefi, M. Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment. Life Sci., 2019, 233116733
[http://dx.doi.org/10.1016/j.lfs.2019.116733] [PMID: 31394127]
[131]
Cui, G.H.; Guo, H.D.; Li, H.; Zhai, Y.; Gong, Z.B.; Wu, J.; Liu, J.S.; Dong, Y.R.; Hou, S.X.; Liu, J.R. RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease. Immun. Ageing, 2019, 16(1), 10.
[http://dx.doi.org/10.1186/s12979-019-0150-2] [PMID: 31114624]
[132]
Zhdanova, D.Y.; Poltavtseva, R.; Svirshchevskaya, E.; Bobkova, N. Effect of intranasal administration of multipotent mesenchymal stromal cell exosomes on memory of mice in alzheimer’s disease model. Bull. Exp. Biol. Med., 2021, 1-8.
[133]
Guo, M.; Yin, Z.; Chen, F.; Lei, P. Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease. Alzheimers Res. Ther., 2020, 12(1), 109.
[http://dx.doi.org/10.1186/s13195-020-00670-x] [PMID: 32928293]
[134]
Gowen, A.; Shahjin, F.; Chand, S.; Odegaard, K.E.; Yelamanchili, S.V. Mesenchymal stem cell-derived extracellular vesicles: challenges in clinical applications. Front. Cell Dev. Biol., 2020, 8, 149.
[http://dx.doi.org/10.3389/fcell.2020.00149] [PMID: 32226787]
[135]
Wu, P.; Gao, W.; Su, M.; Nice, E.C.; Zhang, W.; Lin, J.; Xie, N. Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment. Front. Cell Dev. Biol., 2021, 9641469
[http://dx.doi.org/10.3389/fcell.2021.641469] [PMID: 33732706]
[136]
Foye, C.; Yan, I.K.; David, W.; Shukla, N.; Habboush, Y.; Chase, L.; Ryland, K.; Kesari, V.; Patel, T. Comparison of miRNA quantitation by Nanostring in serum and plasma samples. PLoS One, 2017, 12(12)e0189165
[http://dx.doi.org/10.1371/journal.pone.0189165] [PMID: 29211799]
[137]
Khan, T.K.; Alkon, D.L. Alzheimer’s disease cerebrospinal fluid and neuroimaging biomarkers: diagnostic accuracy and relationship to drug efficacy. J. Alzheimers Dis., 2015, 46(4), 817-836.
[http://dx.doi.org/10.3233/JAD-150238] [PMID: 26402622]
[138]
Coenen-Stass, A.M.L.; Pauwels, M.J.; Hanson, B.; Martin Perez, C.; Conceição, M.; Wood, M.J.A.; Mäger, I.; Roberts, T.C. Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics. RNA Biol., 2019, 16(5), 696-706.
[http://dx.doi.org/10.1080/15476286.2019.1582956] [PMID: 30836828]
[139]
Takahashi, R.H.; Milner, T.A.; Li, F.; Nam, E.E.; Edgar, M.A.; Yamaguchi, H.; Beal, M.F.; Xu, H.; Greengard, P.; Gouras, G.K. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am. J. Pathol., 2002, 161(5), 1869-1879.
[http://dx.doi.org/10.1016/S0002-9440(10)64463-X] [PMID: 12414533]
[140]
Joshi, P.; Benussi, L.; Furlan, R.; Ghidoni, R.; Verderio, C. Extracellular vesicles in Alzheimer’s disease: friends or foes? Focus on aβ-vesicle interaction. Int. J. Mol. Sci., 2015, 16(3), 4800-4813.
[http://dx.doi.org/10.3390/ijms16034800] [PMID: 25741766]
[141]
Cheng, L.; Wu, S.; Zhang, K.; Qing, Y.; Xu, T. A comprehensive overview of exosomes in ovarian cancer: emerging biomarkers and therapeutic strategies. J. Ovarian Res., 2017, 10(1), 73.
[http://dx.doi.org/10.1186/s13048-017-0368-6] [PMID: 29100532]
[142]
Yuyama, K.; Igarashi, Y. Exosomes as carriers of Alzheimer’s amyloid-ß. Front. Neurosci., 2017, 11, 229.
[http://dx.doi.org/10.3389/fnins.2017.00229] [PMID: 28487629]
[143]
Miranda, A.M.; Lasiecka, Z.M.; Xu, Y.; Neufeld, J.; Shahriar, S.; Simoes, S.; Chan, R.B.; Oliveira, T.G.; Small, S.A.; Di Paolo, G. Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures. Nat. Commun., 2018, 9(1), 291.
[http://dx.doi.org/10.1038/s41467-017-02533-w] [PMID: 29348617]
[144]
Wang, G.; Dinkins, M.; He, Q.; Zhu, G.; Poirier, C.; Campbell, A.; Mayer-Proschel, M.; Bieberich, E. Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD). J. Biol. Chem., 2012, 287(25), 21384-21395.
[http://dx.doi.org/10.1074/jbc.M112.340513] [PMID: 22532571]
[145]
Nikitidou, E.; Khoonsari, P.E.; Shevchenko, G.; Ingelsson, M.; Kultima, K.; Erlandsson, A. Increased release of apolipoprotein E in extracellular vesicles following amyloid-β protofibril exposure of neuroglial co-cultures. J. Alzheimers Dis., 2017, 60(1), 305-321.
[http://dx.doi.org/10.3233/JAD-170278] [PMID: 28826183]
[146]
Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol., 2011, 29(4), 341-345.
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[147]
De Toro, J.; Herschlik, L.; Waldner, C.; Mongini, C. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front. Immunol., 2015, 6, 203.
[http://dx.doi.org/10.3389/fimmu.2015.00203] [PMID: 25999947]
[148]
Fiandaca, M.S.; Kapogiannis, D.; Mapstone, M.; Boxer, A.; Eitan, E.; Schwartz, J.B. Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case‐control study. Alzheimers Dement., 2015, 11(6), 600-607.
[http://dx.doi.org/10.1016/j.jalz.2014.06.008]
[149]
Hornung, S.; Dutta, S.; Bitan, G. CNS-Derived blood exosomes as a promising source of biomarkers: opportunities and challenges. Front. Mol. Neurosci., 2020, 13, 38.
[http://dx.doi.org/10.3389/fnmol.2020.00038] [PMID: 32265650]
[150]
Wei, H.; Xu, Y.; Xu, W.; Zhou, Q.; Chen, Q.; Yang, M.; Feng, F.; Liu, Y.; Zhu, X.; Yu, M.; Li, Y. Serum exosomal miR-223 serves as a potential diagnostic and prognostic biomarker for dementia. Neuroscience, 2018, 379, 167-176.
[http://dx.doi.org/10.1016/j.neuroscience.2018.03.016] [PMID: 29559383]
[151]
Gámez-Valero, A.; Campdelacreu, J.; Vilas, D.; Ispierto, L.; Reñé, R.; Álvarez, R.; Armengol, M.P.; Borràs, F.E.; Beyer, K. Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies. Transl. Neurodegener., 2019, 8(1), 31.
[http://dx.doi.org/10.1186/s40035-019-0169-5] [PMID: 31592314]
[152]
Cheng, L.; Doecke, J.D.; Sharples, R.A.; Villemagne, V.L.; Fowler, C.J.; Rembach, A.; Martins, R.N.; Rowe, C.C.; Macaulay, S.L.; Masters, C.L.; Hill, A.F. Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment. Mol. Psychiatry, 2015, 20(10), 1188-1196.
[http://dx.doi.org/10.1038/mp.2014.127] [PMID: 25349172]
[153]
Cha, D.J.; Mengel, D.; Mustapic, M.; Liu, W.; Selkoe, D.J.; Kapogiannis, D.; Galasko, D.; Rissman, R.A.; Bennett, D.A.; Walsh, D.M. miR-212 and miR-132 are down-regulated in neurally-derived plasma exosomes of Alzheimer’s patients. Front. Neurosci., 2019, 13, 1208.
[http://dx.doi.org/10.3389/fnins.2019.01208] [PMID: 31849573]
[154]
Liu, C-G.; Song, J.; Zhang, Y-Q.; Wang, P-C. MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer’s disease. Mol. Med. Rep., 2014, 10(5), 2395-2400.
[http://dx.doi.org/10.3892/mmr.2014.2484] [PMID: 25119742]
[155]
McKeever, P.M.; Schneider, R.; Taghdiri, F.; Weichert, A.; Multani, N.; Brown, R.A.; Boxer, A.L.; Karydas, A.; Miller, B.; Robertson, J.; Tartaglia, M.C. MicroRNA expression levels are altered in the cerebrospinal fluid of patients with young-onset Alzheimer’s disease. Mol. Neurobiol., 2018, 55(12), 8826-8841.
[http://dx.doi.org/10.1007/s12035-018-1032-x] [PMID: 29603092]
[156]
Zakrzewski, W.; Dobrzyński, M.; Szymonowicz, M.; Rybak, Z. Stem cells: past, present, and future. Stem Cell Res. Ther., 2019, 10(1), 68.
[http://dx.doi.org/10.1186/s13287-019-1165-5] [PMID: 30808416]
[157]
Kim, H.J.; Seo, S.W.; Chang, J.W.; Lee, J.I.; Kim, C.H.; Chin, J.; Choi, S.J.; Kwon, H.; Yun, H.J.; Lee, J.M.; Kim, S.T.; Choe, Y.S.; Lee, K.H.; Na, D.L. Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: A phase 1 clinical trial. Alzheimers Dement. (N. Y.), 2015, 1(2), 95-102.
[http://dx.doi.org/10.1016/j.trci.2015.06.007] [PMID: 29854930]
[158]
Inestrosa, N.C.; Reyes, A.E.; Chacón, M.A.; Cerpa, W.; Villalón, A.; Montiel, J.; Merabachvili, G.; Aldunate, R.; Bozinovic, F.; Aboitiz, F. Human-like rodent amyloid-β-peptide determines Alzheimer pathology in aged wild-type Octodon degu. Neurobiol. Aging, 2005, 26(7), 1023-1028.
[http://dx.doi.org/10.1016/j.neurobiolaging.2004.09.016] [PMID: 15748782]
[159]
Zhang, Q.; Li, J.; An, W.; Fan, Y.; Cao, Q. Neural stem cell secretome and its role in the treatment of neurodegenerative disorders. J. Integr. Neurosci., 2020, 19(1), 179-185.
[http://dx.doi.org/10.31083/j.jin.2020.01.1142] [PMID: 32259896]
[160]
Vissers, C.; Ming, G.L.; Song, H. Nanoparticle technology and stem cell therapy team up against neurodegenerative disorders. Adv. Drug Deliv. Rev., 2019, 148, 239-251.
[http://dx.doi.org/10.1016/j.addr.2019.02.007] [PMID: 30797953]
[161]
Jiang, Y.; Zhang, Y.; Zhang, L.; Wang, M.; Zhang, X.; Li, X. Therapeutic effect of bone marrow mesenchymal stem cells on laser-induced retinal injury in mice. Int. J. Mol. Sci., 2014, 15(6), 9372-9385.
[http://dx.doi.org/10.3390/ijms15069372] [PMID: 24871366]
[162]
Yang, J.; Zhang, X.; Chen, X.; Wang, L.; Yang, G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol. Ther. Nucleic Acids, 2017, 7, 278-287.
[http://dx.doi.org/10.1016/j.omtn.2017.04.010] [PMID: 28624203]
[163]
Nassar, W.; El-Ansary, M.; Sabry, D.; Mostafa, M.A.; Fayad, T.; Kotb, E.; Temraz, M.; Saad, A.N.; Essa, W.; Adel, H. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res., 2016, 20(1), 21.
[http://dx.doi.org/10.1186/s40824-016-0068-0] [PMID: 27499886]
[164]
Ezquer, F.; Ezquer, M.; Contador, D.; Ricca, M.; Simon, V.; Conget, P. The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment. Stem Cells, 2012, 30(8), 1664-1674.
[http://dx.doi.org/10.1002/stem.1132] [PMID: 22644660]
[165]
Arena, A.; Iyer, A.M.; Milenkovic, I.; Kovacs, G.G.; Ferrer, I.; Perluigi, M.; Aronica, E. Developmental expression and dysregulation of miR-146a and miR-155 in Down’s syndrome and mouse models of Down’s syndrome and Alzheimer’s disease. Curr. Alzheimer Res., 2017, 14(12), 1305-1317.
[http://dx.doi.org/10.2174/1567205014666170706112701] [PMID: 28720071]
[166]
Manna, I.; De Benedittis, S.; Quattrone, A.; Maisano, D.; Iaccino, E.; Quattrone, A. Exosomal miRNAs as potential diagnostic biomarkers in Alzheimer’s Disease. Pharmaceuticals (Basel), 2020, 13(9), 243.
[http://dx.doi.org/10.3390/ph13090243] [PMID: 32932746]

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