Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Conditioned Media Therapy in Alzheimer's Disease: Current Findings and Future Challenges

Author(s): Amin Firoozi, Mehri Shadi, Zohre Aghaei and Mohammad Reza Namavar*

Volume 19, Issue 5, 2024

Published on: 12 June, 2023

Page: [700 - 711] Pages: 12

DOI: 10.2174/1574888X18666230523155659

Price: $65

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by a reduction in cognition and memory. Till now, there is no definite cure for AD, although, there are treatments available that may improve some symptoms. Currently, in regenerative medicine stem cells are widely used, mainly for treating neurodegenerative diseases. There are numerous forms of stem cells to treat AD aiming at the expansion of the treatment methods for this particular disease. Since 10 years ago, science has gained abundant knowledge to treat AD by understanding the sorts of stem cells, methods, and phasing of injection. Besides, due to the side effects of stem cell therapy like the potentiation for cancer, and as it is hard to follow the cells through the matrix of the brain, researchers have presented a new therapy for AD. They prefer to use conditioned media (CM) that are full of different growth factors, cytokines, chemokines, enzymes, etc. without tumorigenicity or immunogenicity such as stem cells. Another benefit of CM is that CM could be kept in the freezer, easily packaged, and transported, and doesn’t need to fit with the donor. Due to the beneficial effects of CM, in this paper, we intend to evaluate the effects of various types of CM of stem cells on AD.

Keywords: Alzheimer’s disease, Conditioned media, Stem cell, Neurodegenerative disease, cytokines, chemokines.

« Previous Next »
Graphical Abstract

[1]
Lei P, Ayton S, Bush AI. The essential elements of Alzheimer’s disease. J Biol Chem 2021; 296: 100105.
[http://dx.doi.org/10.1074/jbc.REV120.008207] [PMID: 33219130]
[2]
Patterson C. World alzheimer report 2018. 2018.
[3]
van der Lee SJ, Wolters FJ, Ikram MK, et al. The effect of APOE and other common genetic variants on the onset of Alzheimer’s disease and dementia: A community-based cohort study. Lancet Neurol 2018; 17(5): 434-44.
[http://dx.doi.org/10.1016/S1474-4422(18)30053-X] [PMID: 29555425]
[4]
Association As. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement 2019; 15(3): 321-87.
[http://dx.doi.org/10.1016/j.jalz.2019.01.010]
[5]
Bateman RJ, Xiong C, Benzinger TLS, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367(9): 795-804.
[http://dx.doi.org/10.1056/NEJMoa1202753] [PMID: 22784036]
[6]
Lange KW, Lange KM, Makulska-Gertruda E, et al. Ketogenic diets and Alzheimer’s disease. Food Sci Hum Wellness 2017; 6(1): 1-9.
[http://dx.doi.org/10.1016/j.fshw.2016.10.003]
[7]
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011; 1(1): a006189.
[http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]
[8]
Kelley BJ, Petersen RC. Alzheimer’s disease and mild cognitive impairment. Neurol Clin 2007; 25(3): 577-609.
[http://dx.doi.org/10.1016/j.ncl.2007.03.008] [PMID: 17659182]
[9]
Holtzman DM, Carrillo MC, Hendrix JA, et al. Tau: From research to clinical development. Alzheimers Dement 2016; 12(10): 1033-9.
[http://dx.doi.org/10.1016/j.jalz.2016.03.018] [PMID: 27154059]
[10]
Gibbons GS, Lee VMY, Trojanowski JQ. Mechanisms of cell-to-cell transmission of pathological tau: A review. JAMA Neurol 2019; 76(1): 101-8.
[http://dx.doi.org/10.1001/jamaneurol.2018.2505] [PMID: 30193298]
[11]
Ittner A, Ittner LM. Dendritic tau in Alzheimer’s disease. Neuron 2018; 99(1): 13-27.
[http://dx.doi.org/10.1016/j.neuron.2018.06.003] [PMID: 30001506]
[12]
Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 2014; 82(4): 756-71.
[http://dx.doi.org/10.1016/j.neuron.2014.05.004] [PMID: 24853936]
[13]
Ryu J, Girigoswami K, Ha C, Ku SH, Park CB. Influence of multiple metal ions on β-amyloid aggregation and dissociation on a solid surface. Biochemistry 2008; 47(19): 5328-35.
[http://dx.doi.org/10.1021/bi800012e] [PMID: 18422346]
[14]
Wallin C, Jarvet J, Biverstål H, et al. Metal ion coordination delays amyloid-β peptide self-assembly by forming an aggregation–inert complex. J Biol Chem 2020; 295(21): 7224-34.
[http://dx.doi.org/10.1074/jbc.RA120.012738] [PMID: 32241918]
[15]
Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 1998; 158(1): 47-52.
[http://dx.doi.org/10.1016/S0022-510X(98)00092-6] [PMID: 9667777]
[16]
Bush AI. The metallobiology of Alzheimer’s disease. Trends Neurosci 2003; 26(4): 207-14.
[http://dx.doi.org/10.1016/S0166-2236(03)00067-5] [PMID: 12689772]
[17]
House E, Collingwood J, Khan A, Korchazkina O, Berthon G, Exley C. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Aβ42 in a manner which may have consequences for metal chelation therapy in Alzheimer’s disease. J Alzheimers Dis 2004; 6(3): 291-301.
[http://dx.doi.org/10.3233/JAD-2004-6310] [PMID: 15201484]
[18]
Garai K, Sengupta P, Sahoo B, Maiti S. Selective destabilization of soluble amyloid β oligomers by divalent metal ions. Biochem Biophys Res Commun 2006; 345(1): 210-5.
[http://dx.doi.org/10.1016/j.bbrc.2006.04.056] [PMID: 16678130]
[19]
Vermunt L, Sikkes SAM, Hout A, et al. Duration of preclinical, prodromal, and dementia stages of Alzheimer’s disease in relation to age, sex, and APOE genotype. Alzheimers Dement 2019; 15(7): 888-98.
[http://dx.doi.org/10.1016/j.jalz.2019.04.001] [PMID: 31164314]
[20]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[21]
Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer’s disease. Am J Med 2007; 120(5): 388-97.
[http://dx.doi.org/10.1016/j.amjmed.2006.08.036] [PMID: 17466645]
[22]
Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 2012; 366(10): 893-903.
[http://dx.doi.org/10.1056/NEJMoa1106668] [PMID: 22397651]
[23]
Grossberg GT, Manes F, Allegri RF, et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): A multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs 2013; 27(6): 469-78.
[http://dx.doi.org/10.1007/s40263-013-0077-7] [PMID: 23733403]
[24]
Cummings JL, Tong G, Ballard C. Treatment combinations for Alzheimer’s disease: Current and future pharmacotherapy options. J Alzheimers Dis 2019; 67(3): 779-94.
[http://dx.doi.org/10.3233/JAD-180766] [PMID: 30689575]
[25]
Pooler AM, Polydoro M, Wegmann S, Nicholls SB, Spires-Jones TL, Hyman BT. Propagation of tau pathology in Alzheimer’s disease: Identification of novel therapeutic targets. Alzheimers Res Ther 2013; 5(5): 49.
[http://dx.doi.org/10.1186/alzrt214] [PMID: 24152385]
[26]
Rosenmann H. Immunotherapy for targeting tau pathology in Alzheimer’s disease and tauopathies. Curr Alzheimer Res 2013; 10(3): 217-28.
[http://dx.doi.org/10.2174/1567205011310030001] [PMID: 23534533]
[27]
Novak P, Schmidt R, Kontsekova E, et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol 2017; 16(2): 123-34.
[http://dx.doi.org/10.1016/S1474-4422(16)30331-3] [PMID: 27955995]
[28]
Ding L, Meng Y, Zhang HY, Yin WC, Yan Y, Cao YP. Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-Aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice. Neurosci Lett 2016; 634: 1-6.
[http://dx.doi.org/10.1016/j.neulet.2016.09.050] [PMID: 27693663]
[29]
Meng Y, Ding L, Zhang H, Yin W, Yan Y, Cao Y. Immunization of Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH vaccine prevents synaptic deficits of Alzheimer’s disease. Behav Brain Res 2017; 332: 64-70.
[http://dx.doi.org/10.1016/j.bbr.2017.05.056] [PMID: 28577919]
[30]
Zhang XY, Meng Y, Yan XJ, Liu S, Wang GQ, Cao YP. Immunization with Aβ3-10-KLH vaccine improves cognitive function and ameliorates mitochondrial dysfunction and reduces Alzheimer’s disease-like pathology in Tg-APPswe/PSEN1dE9 mice. Brain Res Bull 2021; 174: 31-40.
[http://dx.doi.org/10.1016/j.brainresbull.2021.05.019] [PMID: 34044034]
[31]
Ferrucci R, Mameli F, Guidi I, et al. Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Neurology 2008; 71(7): 493-8.
[http://dx.doi.org/10.1212/01.wnl.0000317060.43722.a3] [PMID: 18525028]
[32]
Metkar SK, Girigoswami A, Murugesan R, Girigoswami K. Lumbrokinase for degradation and reduction of amyloid fibrils associated with amyloidosis. J Appl Biomed 2017; 15(2): 96-104.
[http://dx.doi.org/10.1016/j.jab.2017.01.003]
[33]
Metkar SK, Girigoswami A, Bondage DD, Shinde UG, Girigoswami K. The potential of lumbrokinase and serratiopeptidase for the degradation of Aβ 1–42 peptide – an in vitro and in silico approach. Int J Neurosci 2022; 1-12.
[http://dx.doi.org/10.1080/00207454.2022.2089137] [PMID: 35694981]
[34]
Shikama Y, Kitazawa J, Yagihashi N, et al. Localized amyloidosis at the site of repeated insulin injection in a diabetic patient. Intern Med 2010; 49(5): 397-401.
[http://dx.doi.org/10.2169/internalmedicine.49.2633] [PMID: 20190472]
[35]
Gong H, He Z, Peng A, et al. Effects of several quinones on insulin aggregation. Sci Rep 2014; 4(1): 5648.
[http://dx.doi.org/10.1038/srep05648] [PMID: 25008537]
[36]
Hsu RL, Lee KT, Wang JH, Lee LYL, Chen RPY. Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem 2009; 57(2): 503-8.
[http://dx.doi.org/10.1021/jf803072r] [PMID: 19117402]
[37]
Fadl NN, Ahmed HH, Booles HF, Sayed AH. Serrapeptase and nattokinase intervention for relieving Alzheimer’s disease pathophysiology in rat model. Hum Exp Toxicol 2013; 32(7): 721-35.
[http://dx.doi.org/10.1177/0960327112467040] [PMID: 23821590]
[38]
Metkar SK, Girigoswami A, Murugesan R, Girigoswami K. In vitro and in vivo insulin amyloid degradation mediated by Serratiopeptidase. Mater Sci Eng C 2017; 70(Pt 1): 728-35.
[http://dx.doi.org/10.1016/j.msec.2016.09.049] [PMID: 27770948]
[39]
Metkar SK, Girigoswami A, Vijayashree R, Girigoswami K. Attenuation of subcutaneous insulin induced amyloid mass in vivo using Lumbrokinase and Serratiopeptidase. Int J Biol Macromol 2020; 163: 128-34.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.06.256] [PMID: 32615214]
[40]
Dabbagh F, Negahdaripour M, Berenjian A, et al. Nattokinase: Production and application. Appl Microbiol Biotechnol 2014; 98(22): 9199-206.
[http://dx.doi.org/10.1007/s00253-014-6135-3] [PMID: 25348469]
[41]
Ahmed HH, Nevein NF, Karima A, Hamza AH. Miracle enzymes serrapeptase and nattokinase mitigate neuroinflammation and apoptosis associated with Alzheimer’s disease in experimental model. WJPPS 2013; 3: 876-91.
[42]
Iwahara N, Yokokaw K, Saito T, et al. Mesenchymal stem cell-conditioned medium induces microglia into M2 phenotype and promotes amyloid β-phagocytosis. J Neurol Sci 2017; 381: 665.
[http://dx.doi.org/10.1016/j.jns.2017.08.1871]
[43]
Martínez-Morales PL, Revilla A, Ocaña I, et al. Progress in stem cell therapy for major human neurological disorders. Stem Cell Rev 2013; 9(5): 685-99.
[http://dx.doi.org/10.1007/s12015-013-9443-6] [PMID: 23681704]
[44]
Bruno S, Grange C, Collino F, et al. 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]
[45]
Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S. Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 2008; 26(7): 1787-95.
[http://dx.doi.org/10.1634/stemcells.2007-0979] [PMID: 18499892]
[46]
Deregibus MC, Cantaluppi V, Calogero R, et al. Endothelial progenitor cell–derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007; 110(7): 2440-8.
[http://dx.doi.org/10.1182/blood-2007-03-078709] [PMID: 17536014]
[47]
Sahoo S, Klychko E, Thorne T, et al. Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res 2011; 109(7): 724-8.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.253286] [PMID: 21835908]
[48]
Schäfer S, Calas AG, Vergouts M, Hermans E. Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on neuroinflammation in astrocyte cultures. J Neuroimmunol 2012; 249(1-2): 40-8.
[http://dx.doi.org/10.1016/j.jneuroim.2012.04.018] [PMID: 22633273]
[49]
Ma H, Zhang S, Xu Y, Zhang R, Zhang X. Analysis of differentially expressed microRNA of TNF-α-stimulated mesenchymal stem cells and exosomes from their culture supernatant. Arch Med Sci 2018; 14(5): 1102-11.
[http://dx.doi.org/10.5114/aoms.2017.70878] [PMID: 30154894]
[50]
Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. BioMed Res Int 2014; 2014: 965849.
[http://dx.doi.org/10.1155/2014/965849]
[51]
Park D, Yang G, Bae DK, et al. Human adipose tissue-derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice. J Neurosci Res 2013; 91(5): 660-70.
[http://dx.doi.org/10.1002/jnr.23182] [PMID: 23404260]
[52]
Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae J. 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.
[http://dx.doi.org/10.1002/stem.277] [PMID: 20014009]
[53]
Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng Part A 2012; 18(13-14): 1479-89.
[http://dx.doi.org/10.1089/ten.tea.2011.0325] [PMID: 22443121]
[54]
Katagiri W, Osugi M, Kawai T, Ueda M. Novel cell-free regeneration of bone using stem cell-derived growth factors. Int J Oral Maxillofac Implants 2013; 28(4): 1009-16.
[http://dx.doi.org/10.11607/jomi.3036] [PMID: 23869359]
[55]
Cantinieaux D, Quertainmont R, Blacher S, et al. Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: An original strategy to avoid cell transplantation. PLoS One 2013; 8(8): e69515.
[http://dx.doi.org/10.1371/journal.pone.0069515] [PMID: 24013448]
[56]
Chen L, Xu Y, Zhao J, et al. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice. PLoS One 2014; 9(4): e96161.
[http://dx.doi.org/10.1371/journal.pone.0096161] [PMID: 24781370]
[57]
Kuo SC, Chio CC, Yeh CH, et al. Mesenchymal stem cell‐conditioned medium attenuates the retinal pathology in amyloid‐β‐induced rat model of Alzheimer’s disease: Underlying mechanisms. Aging Cell 2021; 20(5): e13340.
[http://dx.doi.org/10.1111/acel.13340] [PMID: 33783931]
[58]
Thomas T, Miners S, Love S. Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer’s disease and vascular dementia. Brain 2015; 138(4): 1059-69.
[http://dx.doi.org/10.1093/brain/awv025] [PMID: 25688080]
[59]
Miners JS, Schulz I, Love S. Differing associations between Aβ accumulation, hypoperfusion, blood–brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer’s disease. J Cereb Blood Flow Metab 2018; 38(1): 103-15.
[http://dx.doi.org/10.1177/0271678X17690761] [PMID: 28151041]
[60]
Provias J, Jeynes B. Reduction in vascular endothelial growth factor expression in the superior temporal, hippocampal, and brainstem regions in Alzheimer’s disease. Curr Neurovasc Res 2014; 11(3): 202-9.
[http://dx.doi.org/10.2174/1567202611666140520122316] [PMID: 24845858]
[61]
Noshita T, Murayama N, Oka T, Ogino R, Nakamura S, Inoue T. Effect of bFGF on neuronal damage induced by sequential treatment of amyloid β and excitatory amino acid in vitro and in vivo. Eur J Pharmacol 2012; 695(1-3): 76-82.
[http://dx.doi.org/10.1016/j.ejphar.2012.09.020] [PMID: 23026373]
[62]
Abe K, Saito H. Effects of basic fibroblast growth factor on central nervous system functions. Pharmacol Res 2001; 43(4): 307-12.
[http://dx.doi.org/10.1006/phrs.2000.0794] [PMID: 11352534]
[63]
Zhang C, Chen J, Feng C, et al. Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer’s disease. Int J Pharm 2014; 461(1-2): 192-202.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.049] [PMID: 24300213]
[64]
Wang Y, Yan W, Lu X, et al. Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the avβ3/PI3K/AKT/eNOS/NO signaling pathway in glioma cells. Eur J Cell Biol 2011; 90(8): 642-8.
[http://dx.doi.org/10.1016/j.ejcb.2011.03.005] [PMID: 21616556]
[65]
Dai J, Peng L, Fan K, et al. Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene 2009; 28(38): 3412-22.
[http://dx.doi.org/10.1038/onc.2009.189] [PMID: 19597469]
[66]
Lederle W, Hartenstein B, Meides A, et al. MMP13 as a stromal mediator in controlling persistent angiogenesis in skin carcinoma. Carcinogenesis 2010; 31(7): 1175-84.
[http://dx.doi.org/10.1093/carcin/bgp248] [PMID: 19892798]
[67]
Li W-M, Chen W-B. Effect of FGF-BP on angiogenesis in squamous cell carcinoma. Chin Med J 2004; 117(4): 621-3.
[PMID: 15109463]
[68]
Harris VK, Coticchia CM, Kagan BL, Ahmad S, Wellstein A, Riegel AT. Induction of the angiogenic modulator fibroblast growth factor-binding protein by epidermal growth factor is mediated through both MEK/ERK and p38 signal transduction pathways. J Biol Chem 2000; 275(15): 10802-11.
[http://dx.doi.org/10.1074/jbc.275.15.10802] [PMID: 10753873]
[69]
Sainaghi PP, Bellan M, Lombino F, et al. Growth arrest specific 6 concentration is increased in the cerebrospinal fluid of patients with Alzheimer’s disease. J Alzheimers Dis 2016; 55(1): 59-65.
[http://dx.doi.org/10.3233/JAD-160599] [PMID: 27636849]
[70]
Tondo G, Perani D, Comi C. TAM receptor pathways at the crossroads of neuroinflammation and neurodegeneration. Dis Markers 2019; 2019: 2387614.
[http://dx.doi.org/10.1155/2019/2387614]
[71]
Ma X, Huang M, Zheng M, et al. ADSCs-derived extracellular vesicles alleviate neuronal damage, promote neurogenesis and rescue memory loss in mice with Alzheimer’s disease. J Control Release 2020; 327: 688-702.
[http://dx.doi.org/10.1016/j.jconrel.2020.09.019] [PMID: 32931898]
[72]
Gadelkarim M, Abushouk AI, Ghanem E, Hamaad AM, Saad AM, Abdel-Daim MM. Adipose-derived stem cells: Effectiveness and advances in delivery in diabetic wound healing. Biomed Pharmacother 2018; 107: 625-33.
[http://dx.doi.org/10.1016/j.biopha.2018.08.013] [PMID: 30118878]
[73]
Lee M, Ban JJ, Yang S, Im W, Kim M. The exosome of adipose-derived stem cells reduces β-amyloid pathology and apoptosis of neuronal cells derived from the transgenic mouse model of Alzheimer’s disease. Brain Res 2018; 1691: 87-93.
[http://dx.doi.org/10.1016/j.brainres.2018.03.034] [PMID: 29625119]
[74]
Wei X, Zhao L, Zhong J, et al. Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis. Neurosci Lett 2009; 462(1): 76-9.
[http://dx.doi.org/10.1016/j.neulet.2009.06.054] [PMID: 19549558]
[75]
Egashira Y, Sugitani S, Suzuki Y, et al. The conditioned medium of murine and human adipose-derived stem cells exerts neuroprotective effects against experimental stroke model. Brain Res 2012; 1461: 87-95.
[http://dx.doi.org/10.1016/j.brainres.2012.04.033] [PMID: 22608076]
[76]
Ikegame Y, Yamashita K, Hayashi SI, et al. Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy 2011; 13(6): 675-85.
[http://dx.doi.org/10.3109/14653249.2010.549122] [PMID: 21231804]
[77]
Yamazaki H, Jin Y, Tsuchiya A, Kanno T, Nishizaki T. Adipose-derived stem cell-conditioned medium ameliorates antidepression-related behaviors in the mouse model of Alzheimer’s disease. Neurosci Lett 2015; 609: 53-7.
[http://dx.doi.org/10.1016/j.neulet.2015.10.023] [PMID: 26472709]
[78]
Guillén MI, Platas J, Pérez del Caz MD, Mirabet V, Alcaraz MJ. Paracrine anti-inflammatory effects of adipose tissue-derived mesenchymal stem cells in human monocytes. Front Physiol 2018; 9: 661.
[http://dx.doi.org/10.3389/fphys.2018.00661] [PMID: 29904354]
[79]
Zheng C, Nennesmo I, Fadeel B, Henter JI. Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Ann Neurol 2004; 56(4): 564-7.
[http://dx.doi.org/10.1002/ana.20223] [PMID: 15389897]
[80]
Mehrabadi S, Motevaseli E, Sadr SS, Moradbeygi K. Hypoxic-conditioned medium from adipose tissue mesenchymal stem cells improved neuroinflammation through alternation of toll like receptor (TLR) 2 and TLR4 expression in model of Alzheimer’s disease rats. Behav Brain Res 2020; 379: 112362.
[http://dx.doi.org/10.1016/j.bbr.2019.112362] [PMID: 31739000]
[81]
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci 2000; 97(25): 13625-30.
[http://dx.doi.org/10.1073/pnas.240309797] [PMID: 11087820]
[82]
Miura M, Gronthos S, Zhao M, et al. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci 2003; 100(10): 5807-12.
[http://dx.doi.org/10.1073/pnas.0937635100] [PMID: 12716973]
[83]
Sakai K, Yamamoto A, Matsubara K, et al. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Invest 2012; 122(1): 80-90.
[PMID: 22133879]
[84]
Király M, Porcsalmy B, Pataki Á, et al. Simultaneous PKC and cAMP activation induces differentiation of human dental pulp stem cells into functionally active neurons. Neurochem Int 2009; 55(5): 323-32.
[http://dx.doi.org/10.1016/j.neuint.2009.03.017] [PMID: 19576521]
[85]
Taghipour Z, Karbalaie K, Kiani A, et al. Transplantation of undifferentiated and induced human exfoliated deciduous teeth-derived stem cells promote functional recovery of rat spinal cord contusion injury model. Stem Cells Dev 2012; 21(10): 1794-802.
[http://dx.doi.org/10.1089/scd.2011.0408] [PMID: 21970342]
[86]
de Almeida FM, Marques SA, Ramalho BS, et al. Human dental pulp cells: A new source of cell therapy in a mouse model of compressive spinal cord injury. J Neurotrauma 2011; 28(9): 1939-49.
[http://dx.doi.org/10.1089/neu.2010.1317] [PMID: 21609310]
[87]
Leong WK, Henshall TL, Arthur A, et al. Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms. Stem Cells Transl Med 2012; 1(3): 177-87.
[http://dx.doi.org/10.5966/sctm.2011-0039] [PMID: 23197777]
[88]
Inoue T, Sugiyama M, Hattori H, Wakita H, Wakabayashi T, Ueda M. Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats. Tissue Eng Part A 2013; 19(1-2): 24-9.
[http://dx.doi.org/10.1089/ten.tea.2011.0385] [PMID: 22839964]
[89]
Yamagata M, Yamamoto A, Kako E, et al. Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke 2013; 44(2): 551-4.
[http://dx.doi.org/10.1161/STROKEAHA.112.676759] [PMID: 23238858]
[90]
Yamamoto A, Sakai K, Matsubara K, Kano F, Ueda M. Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury. Neurosci Res 2014; 78: 16-20.
[http://dx.doi.org/10.1016/j.neures.2013.10.010] [PMID: 24252618]
[91]
Mita T, Furukawa-Hibi Y, Takeuchi H, et al. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease. Behav Brain Res 2015; 293: 189-97.
[http://dx.doi.org/10.1016/j.bbr.2015.07.043] [PMID: 26210934]
[92]
Lu B, Gottschalk W. Modulation of hippocampal synaptic transmission and plasticity by neurotrophins. Prog Brain Res 2000; 128: 231-41.
[http://dx.doi.org/10.1016/S0079-6123(00)28020-5] [PMID: 11105682]
[93]
Lu Y, Christian K, Lu B. BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 2008; 89(3): 312-23.
[http://dx.doi.org/10.1016/j.nlm.2007.08.018] [PMID: 17942328]
[94]
Ozawa T, Yamada K, Ichitani Y. Hippocampal BDNF treatment facilitates consolidation of spatial memory in spontaneous place recognition in rats. Behav Brain Res 2014; 263: 210-6.
[http://dx.doi.org/10.1016/j.bbr.2014.01.034] [PMID: 24503120]
[95]
Nutt JG, Burchiel KJ, Comella CL, et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 2003; 60(1): 69-73.
[http://dx.doi.org/10.1212/WNL.60.1.69] [PMID: 12525720]
[96]
Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 2013; 138(2): 155-75.
[http://dx.doi.org/10.1016/j.pharmthera.2013.01.004] [PMID: 23348013]
[97]
Konishi Y, Yang LB, He P, et al. Deficiency of GDNF receptor GFRα1 in Alzheimer’s neurons results in neuronal death. J Neurosci 2014; 34(39): 13127-38.
[http://dx.doi.org/10.1523/JNEUROSCI.2582-13.2014] [PMID: 25253858]
[98]
Rocha SM, Cristovão AC, Campos FL, Fonseca CP, Baltazar G. Astrocyte-derived GDNF is a potent inhibitor of microglial activation. Neurobiol Dis 2012; 47(3): 407-15.
[http://dx.doi.org/10.1016/j.nbd.2012.04.014] [PMID: 22579772]
[99]
Iannotti C, Li H, Yan P, Lu X, Wirthlin L, Xu X-M. Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury. Exp Neurol 2003; 183(2): 379-93.
[http://dx.doi.org/10.1016/S0014-4886(03)00188-2] [PMID: 14552879]
[100]
Jourquin J, Tremblay E, Bernard A, et al. Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory. Eur J Neurosci 2005; 22(10): 2569-78.
[http://dx.doi.org/10.1111/j.1460-9568.2005.04426.x] [PMID: 16307599]
[101]
Niimura M, Takagi N, Takagi K, et al. The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. Neurosci Lett 2006; 407(2): 136-40.
[http://dx.doi.org/10.1016/j.neulet.2006.08.060] [PMID: 16973282]
[102]
Li JW, Li LL, Chang LL, Wang ZY, Xu Y. Stem cell factor protects against neuronal apoptosis by activating AKT/ERK in diabetic mice. Braz J Med Biol Res 2009; 42(11): 1044-9.
[http://dx.doi.org/10.1590/S0100-879X2009005000031] [PMID: 19802467]
[103]
Fragkouli A, Tsilibary EC, Tzinia AK. Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer’s 5xFAD mice. Neurobiol Dis 2014; 70: 179-89.
[http://dx.doi.org/10.1016/j.nbd.2014.06.021] [PMID: 25008761]
[104]
Rubio-Perez JM, Morillas-Ruiz JM. A review: Inflammatory process in Alzheimer’s disease, role of cytokines. ScientificWorldJournal 2012; 2012: 756357.
[http://dx.doi.org/10.1100/2012/756357]
[105]
Ahmed NE-MB, Murakami M, Hirose Y, Nakashima M. Therapeutic potential of dental pulp stem cell secretome for Alzheimer’s disease treatment: An in vitro study. Stem Cells Int 2016; 2016: 8102478.
[http://dx.doi.org/10.1155/2016/8102478]
[106]
Man RC, Sulaiman N, Idrus RBH, Ariffin SHZ, Wahab RMA, Yazid MD. Insights into the effects of the dental stem cell secretome on nerve regeneration: Towards cell-free treatment. Stem Cells Int 2019; 2019: 4596150.
[107]
Cheng Y, Zhang J, Deng L, et al. Intravenously delivered neural stem cells migrate into ischemic brain, differentiate and improve functional recovery after transient ischemic stroke in adult rats. Int J Clin Exp Pathol 2015; 8(3): 2928-36.
[PMID: 26045801]
[108]
Ratajczak MZ, Kucia M, Jadczyk T, et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies? Leukemia 2012; 26(6): 1166-73.
[http://dx.doi.org/10.1038/leu.2011.389] [PMID: 22182853]
[109]
Yoon B-W, Ryu S, Lee S-H, Kim SU. Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain. Neural Regen Res 2016; 11(2): 298-304.
[http://dx.doi.org/10.4103/1673-5374.177739] [PMID: 27073384]
[110]
Talaverón R, Matarredona ER, de la Cruz RR, Pastor AM. Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons. PLoS One 2013; 8(1): e54519.
[http://dx.doi.org/10.1371/journal.pone.0054519] [PMID: 23349916]
[111]
Lu P, Jones LL, Snyder EY, Tuszynski MH. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 2003; 181(2): 115-29.
[http://dx.doi.org/10.1016/S0014-4886(03)00037-2] [PMID: 12781986]
[112]
Schindler SM, Little JP, Klegeris A. Microparticles: A new perspective in central nervous system disorders. BioMed Res Int 2014; 2014: 756327.
[http://dx.doi.org/10.1155/2014/756327]
[113]
Krämer-Albers EM, Kuo-Elsner PW. Extracellular vesicles: Goodies for the brain? Neuropsychopharmacology 2016; 41(1): 371-2.
[http://dx.doi.org/10.1038/npp.2015.242] [PMID: 26657950]
[114]
Porro C, Trotta T, Panaro MA. Microvesicles in the brain: Biomarker, messenger or mediator? J Neuroimmunol 2015; 288: 70-8.
[http://dx.doi.org/10.1016/j.jneuroim.2015.09.006] [PMID: 26531697]
[115]
Yang H, Wang C, Chen H, Li L, Ma S, Wang H. Neural stem cell-conditioned medium ameliorated cerebral ischemia-reperfusion injury in rats. Stem Cells Int 2018; 2018: 4659159.
[http://dx.doi.org/10.1155/2018/4659159]
[116]
Yang H, Wang J, Sun J, Liu X, Duan WM, Qu T. A new method to effectively and rapidly generate neurons from SH-SY5Y cells. Neurosci Lett 2016; 610: 43-7.
[http://dx.doi.org/10.1016/j.neulet.2015.10.047] [PMID: 26497914]
[117]
Liang P, Liu J, Xiong J, et al. Neural stem cell-conditioned medium protects neurons and promotes propriospinal neurons relay neural circuit reconnection after spinal cord injury. Cell Transplant 2014; 23(S1): 45-56.
[http://dx.doi.org/10.3727/096368914X684989] [PMID: 25333841]
[118]
Cheng Z, Bosco DB, Sun L, et al. Neural stem cell-conditioned medium suppresses inflammation and promotes spinal cord injury recovery. Cell Transplant 2017; 26(3): 469-82.
[http://dx.doi.org/10.3727/096368916X693473] [PMID: 27737726]
[119]
Jia G, Yang H, Diao Z, Liu Y, Sun C. Neural stem cell conditioned medium alleviates Aβ25-35 damage to SH-SY5Y cells through the PCMT1/MST1 pathway. Eur J Histochem 2020; 64(S2): 3135.
[120]
Jia Y, Cao N, Zhai J, et al. HGF mediates clinical‐grade human umbilical cord‐derived mesenchymal stem cells improved functional recovery in a senescence‐accelerated mouse model of Alzheimer’s disease. Adv Sci 2020; 7(17): 1903809.
[http://dx.doi.org/10.1002/advs.201903809] [PMID: 32995116]
[121]
Kim JY, Kim DH, Kim JH, et al. Umbilical cord blood mesenchymal stem cells protect amyloid-β42 neurotoxicity via paracrine. World J Stem Cells 2012; 4(11): 110-6.
[http://dx.doi.org/10.4252/wjsc.v4.i11.110] [PMID: 23293711]
[122]
Kim JY, Kim DH, Kim DS, et al. Galectin-3 secreted by human umbilical cord blood-derived mesenchymal stem cells reduces amyloid-beta42 neurotoxicity in vitro. Biophys J 2011; 100(3): 415a.
[http://dx.doi.org/10.1016/j.bpj.2010.12.2460]
[123]
Kim DH, Lee D, Chang EH, et al. 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): 2378-90.
[http://dx.doi.org/10.1089/scd.2014.0487] [PMID: 26154268]
[124]
Kim DH, Lim H, Lee D, et al. Thrombospondin-1 secreted by human umbilical cord blood-derived mesenchymal stem cells rescues neurons from synaptic dysfunction in Alzheimer’s disease model. Sci Rep 2018; 8(1): 354.
[http://dx.doi.org/10.1038/s41598-017-18542-0] [PMID: 29321508]
[125]
Kim J-Y, Kim DH, Kim JH, et al. Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-β plaques. Cell Death Differ 2012; 19(4): 680-91.
[http://dx.doi.org/10.1038/cdd.2011.140] [PMID: 22015609]
[126]
Kim DH, Lee D, Lim H, et al. Effect of growth differentiation factor-15 secreted by human umbilical cord blood-derived mesenchymal stem cells on amyloid beta levels in in vitro and in vivo models of Alzheimer’s disease. Biochem Biophys Res Commun 2018; 504(4): 933-40.
[http://dx.doi.org/10.1016/j.bbrc.2018.09.012] [PMID: 30224067]
[127]
Weiss A, Attisano L. The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol 2013; 2(1): 47-63.
[http://dx.doi.org/10.1002/wdev.86] [PMID: 23799630]
[128]
Li MO, Wan YY, Sanjabi S, Robertson AKL, Flavell RA. Transforming growth factor-β regulation of immune responses. Annu Rev Immunol 2006; 24(1): 99-146.
[http://dx.doi.org/10.1146/annurev.immunol.24.021605.090737] [PMID: 16551245]
[129]
Caraci F, Spampinato S, Sortino MA, et al. Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection. Cell Tissue Res 2012; 347(1): 291-301.
[http://dx.doi.org/10.1007/s00441-011-1230-6] [PMID: 21879289]
[130]
Lawler J. Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth. J Cell Mol Med 2002; 6(1): 1-12.
[http://dx.doi.org/10.1111/j.1582-4934.2002.tb00307.x] [PMID: 12003665]
[131]
Ikeda H, Miyatake M, Koshikawa N, et al. Morphine modulation of thrombospondin levels in astrocytes and its implications for neurite outgrowth and synapse formation. J Biol Chem 2010; 285(49): 38415-27.
[http://dx.doi.org/10.1074/jbc.M110.109827] [PMID: 20889977]
[132]
Xu J, Xiao N, Xia J. Thrombospondin 1 accelerates synaptogenesis in hippocampal neurons through neuroligin 1. Nat Neurosci 2010; 13(1): 22-4.
[http://dx.doi.org/10.1038/nn.2459] [PMID: 19915562]
[133]
Lu Z, Kipnis J. Thrombospondin 1-a key astrocyte‐derived neurogenic factor. FASEB J 2010; 24(6): 1925-34.
[http://dx.doi.org/10.1096/fj.09-150573] [PMID: 20124433]
[134]
Garcia O, Torres M, Helguera P, Coskun P, Busciglio J. A role for thrombospondin-1 deficits in astrocyte-mediated spine and synaptic pathology in Down’s syndrome. PLoS One 2010; 5(12): e14200.
[http://dx.doi.org/10.1371/journal.pone.0014200] [PMID: 21152035]
[135]
Tyzack GE, Sitnikov S, Barson D, et al. Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression. Nat Commun 2014; 5(1): 4294.
[http://dx.doi.org/10.1038/ncomms5294] [PMID: 25014177]
[136]
Cheng C, Lau SKM, Doering LC. Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model. Mol Brain 2016; 9(1): 74.
[http://dx.doi.org/10.1186/s13041-016-0256-9] [PMID: 27485117]
[137]
Xu Z, Nan W, Zhang X, et al. Umbilical cord mesenchymal stem cells conditioned medium promotes Aβ25-35 phagocytosis by modulating autophagy and aβ-degrading enzymes in BV2 cells. J Mol Neurosci 2018; 65(2): 222-33.
[http://dx.doi.org/10.1007/s12031-018-1075-5] [PMID: 29845511]

Rights & Permissions Print Cite
Article Metrics
14
2
© 2024 Bentham Science Publishers | Privacy Policy