Functional Mechanism of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Animal Models with Alzheimer’s Disease: Inhibition of Neuroinflammation

References

• Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362(4):329–344. doi:10.1056/NEJMra0909142
   PubMed Web of Science ®Google Scholar
• Tang M, Ryman DC, McDade E, et al. Neurological manifestations of autosomal dominant familial Alzheimer’s disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). Lancet Neurol. 2016;15(13):1317–1325. doi:10.1016/S1474-4422(16)30229-0
   PubMed Web of Science ®Google Scholar
• Fertan E, Rodrigues GJ, Wheeler RV, et al. Cognitive Decline, Cerebral-Spleen Tryptophan Metabolism, Oxidative Stress, Cytokine Production, and Regulation of the Txnip Gene in a Triple Transgenic Mouse Model of Alzheimer Disease. Am J Pathol. 2019;189(7):1435–1450. doi:10.1016/j.ajpath.2019.03.006
   PubMed Web of Science ®Google Scholar
• Polito VA, Li H, Martini-Stoica H, et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med. 2014;6(9):1142–1160. doi:10.15252/emmm.201303671
   PubMed Web of Science ®Google Scholar
• Sajjad N, Wani A, Sharma A, et al. Artemisia amygdalina Upregulates Nrf2 and Protects Neurons Against Oxidative Stress in Alzheimer Disease. Cell Mol Neurobiol. 2019;39(3):387–399. doi:10.1007/s10571-019-00656-w
   PubMed Web of Science ®Google Scholar
• Santos RX, Correia SC, Wang X, et al. A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease. J Alzheimers Dis. 2010;20(Suppl 2):S401–12. doi:10.3233/JAD-2010-100666
   PubMed Web of Science ®Google Scholar
• Ko YJ, Ko IG. Voluntary Wheel Running Improves Spatial Learning Memory by Suppressing Inflammation and Apoptosis via Inactivation of Nuclear Factor Kappa B in Brain Inflammation Rats. Int Neurourol J. 2020;24(Suppl 2):96–103. doi:10.5213/inj.2040432.216
   PubMedGoogle Scholar
• Alexandraki KI, Apostolopoulos NV, Adamopoulos C, et al. Differential Expression of Apoptotic and Low-Grade Inflammatory Markers in Alzheimer Disease Compared to Diabetes Mellitus Type 1 and 2. J Appl Lab Med. 2019;3(6):1003–1013. doi:10.1373/jalm.2018.027623
   PubMedGoogle Scholar
• Kim SH, Ko YJ, Kim JY, Sim YJ. Treadmill Running Improves Spatial Learning Memory Through Inactivation of Nuclear Factor Kappa B/Mitogen-Activated Protein Kinase Signaling Pathway in Amyloid-beta-Induced Alzheimer Disease Rats. Int Neurourol J. 2021;25(Suppl 1):S35–43. doi:10.5213/inj.2142164.082
   PubMedGoogle Scholar
• Verma S, Kumar A, Tripathi T, Kumar A. Muscarinic and nicotinic acetylcholine receptor agonists: current scenario in Alzheimer’s disease therapy. J Pharm Pharmacol. 2018;70(8):985–993. doi:10.1111/jphp.12919
   PubMed Web of Science ®Google Scholar
• Connelly PJ, Adams F, Tayar ZI, Khan F. Peripheral vascular responses to acetylcholine as a predictive tool for response to cholinesterase inhibitors in Alzheimer’s disease. BMC Neurol. 2019;19(1):88. doi:10.1186/s12883-019-1316-4
   PubMedGoogle Scholar
• Huber CM, Yee C, May T, Dhanala A, Mitchell CS. Cognitive Decline in Preclinical Alzheimer’s Disease: amyloid-Beta versus Tauopathy. J Alzheimers Dis. 2018;61(1):265–281. doi:10.3233/JAD-170490
   PubMed Web of Science ®Google Scholar
• White JD, Urbano CM, Taylor JO, et al. Intraventricular murine Abeta infusion elicits hippocampal inflammation and disrupts the consolidation, but not retrieval, of conditioned fear in C57BL6/J mice. Behav Brain Res. 2020;378:112303. doi:10.1016/j.bbr.2019.112303
   PubMed Web of Science ®Google Scholar
• Huang HJ, Chen SL, Huang HY, et al. Chronic low dose of AM404 ameliorates the cognitive impairment and pathological features in hyperglycemic 3xTg-AD mice. Psychopharmacol Berl. 2019;236(2):763–773. doi:10.1007/s00213-018-5108-0
   PubMed Web of Science ®Google Scholar
• Lee M, Ban JJ, Yang S, Im W, Kim M. The exosome of adipose-derived stem cells reduces beta-amyloid pathology and apoptosis of neuronal cells derived from the transgenic mouse model of Alzheimer’s disease. Brain Res. 2018;1691:87–93. doi:10.1016/j.brainres.2018.03.034
   PubMed Web of Science ®Google Scholar
• Ehrhart J, Darlington D, Kuzmin-Nichols N, et al. Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer’s Disease-Like Murine Model. Cell Transpl. 2016;25(1):195–199. doi:10.3727/096368915X689604
   PubMed Web of Science ®Google Scholar
• Reyes S, Tajiri N, Borlongan CV. Developments in intracerebral stem cell grafts. Expert Rev Neurother. 2015;15(4):381–393. doi:10.1586/14737175.2015.1021787
   PubMed Web of Science ®Google Scholar
• Cha MY, Kwon YW, Ahn HS, et al. Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Abeta Deposition in a Mouse Model of Alzheimer’s Disease. Stem Cells Transl Med. 2017;6(1):293–305. doi:10.5966/sctm.2016-0081
   PubMed Web of Science ®Google Scholar
• Fujiwara N, Shimizu J, Takai K, et al. Cellular and molecular mechanisms of the restoration of human APP transgenic mouse cognitive dysfunction after transplant of human iPS cell-derived neural cells. Exp Neurol. 2015;271:423–431. doi:10.1016/j.expneurol.2015.07.008
   PubMed Web of Science ®Google Scholar
• Shen Z, Li X, Bao X, Wang R. Microglia-targeted stem cell therapies for Alzheimer disease: a preclinical data review. J Neurosci Res. 2017;95(12):2420–2429. doi:10.1002/jnr.24066
   PubMed Web of Science ®Google Scholar
• Naaldijk Y, Jager C, Fabian C, et al. Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice. Neuropathol Appl Neurobiol. 2017;43(4):299–314. doi:10.1111/nan.12319
   PubMed Web of Science ®Google Scholar
• Bae JS, Jin HK, Lee JK, Richardson JC, Carter JE. Bone marrow-derived mesenchymal stem cells contribute to the reduction of amyloid-beta deposits and the improvement of synaptic transmission in a mouse model of pre-dementia Alzheimer’s disease. Curr Alzheimer Res. 2013;10(5):524–531. doi:10.2174/15672050113109990027
   PubMed Web of Science ®Google Scholar
• Tang X, Chen F, Lin Q, You Y, Ke J, Zhao S. Bone marrow mesenchymal stem cells repair the hippocampal neurons and increase the expression of IGF-1 after cardiac arrest in rats. Exp Ther Med. 2017;14(5):4312–4320. doi:10.3892/etm.2017.5059
   PubMed Web of Science ®Google Scholar
• Hammond TR, Dufort C, Dissing-Olesen L, et al. Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes. Immunity. 2019;50(1):253–271 e6. doi:10.1016/j.immuni.2018.11.004
   PubMed Web of Science ®Google Scholar
• Regmi S, Pathak S, Kim JO, Yong CS, Jeong JH. Mesenchymal stem cell therapy for the treatment of inflammatory diseases: challenges, opportunities, and future perspectives. Eur J Cell Biol. 2019;98(5–8):151041. doi:10.1016/j.ejcb.2019.04.002
   PubMed Web of Science ®Google Scholar
• Qin C, Lu Y, Wang K, et al. Transplantation of bone marrow mesenchymal stem cells improves cognitive deficits and alleviates neuropathology in animal models of Alzheimer’s disease: a meta-analytic review on potential mechanisms. Transl Neurodegener. 2020;9(1):20. doi:10.1186/s40035-020-00199-x
   PubMed Web of Science ®Google Scholar
• Danielyan L, Beer-Hammer S, Stolzing A, et al. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease. Cell Transpl. 2014;23(Suppl 1):S123–39. doi:10.3727/096368914X684970
   PubMedGoogle Scholar
• Wang X, Ma S, Yang B, et al. Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease. Behav Brain Res. 2018;339:297–304. doi:10.1016/j.bbr.2017.10.032
   PubMed Web of Science ®Google Scholar
• Liu Z, Wang C, Wang X, Xu S. Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer’s Disease. Cell Physiol Biochem. 2015;37(1):321–330. doi:10.1159/000430356
   PubMedGoogle Scholar
• Nasiri E, Alizadeh A, Roushandeh AM, Gazor R, Hashemi-Firouzi N, Golipoor Z. Melatonin-pretreated adipose-derived mesenchymal stem cells efficiently improved learning, memory, and cognition in an animal model of Alzheimer’s disease. Metab Brain Dis. 2019;34(4):1131–1143. doi:10.1007/s11011-019-00421-4
   PubMed Web of Science ®Google Scholar
• Kanamaru T, Kamimura N, Yokota T, et al. Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer’s disease. Brain Res. 2015;1605:49–58. doi:10.1016/j.brainres.2015.02.011
   PubMed Web of Science ®Google Scholar
• Harach T, Jammes F, Muller C, et al. Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2017;51:83–96. doi:10.1016/j.neurobiolaging.2016.11.009
   PubMed Web of Science ®Google Scholar
• Hwang JH, Shim SS, Seok OS, et al. Comparison of cytokine expression in mesenchymal stem cells from human placenta, cord blood, and bone marrow. J Korean Med Sci. 2009;24(4):547–554. doi:10.3346/jkms.2009.24.4.547
   PubMed Web of Science ®Google Scholar
• Fathi E, Farahzadi R, Valipour B, Sanaat Z. Cytokines secreted from bone marrow derived mesenchymal stem cells promote apoptosis and change cell cycle distribution of K562 cell line as clinical agent in cell transplantation. PLoS One. 2019;14(4):e0215678. doi:10.1371/journal.pone.0215678
   PubMed Web of Science ®Google Scholar
• Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci. 2013;14(9):17986–18001. doi:10.3390/ijms140917986
   PubMed Web of Science ®Google Scholar
• Yoon YS, Wecker A, Heyd L, et al. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest. 2005;115(2):326–338. doi:10.1172/JCI22326
   PubMed Web of Science ®Google Scholar
• Chen Q, Liu Y, Ding X, et al. Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7. Mol Cell Biochem. 2020;465(1–2):103–114. doi:10.1007/s11010-019-03671-z
   PubMed Web of Science ®Google Scholar
• Iso Y, Usui S, Toyoda M, Spees JL, Umezawa A, Suzuki H. Bone marrow-derived mesenchymal stem cells inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia after arterial injury in rats. Biochem Biophys Rep. 2018;16:79–87. doi:10.1016/j.bbrep.2018.10.001
   PubMedGoogle Scholar
• Cho GW, Noh MY, Kim HY, Koh SH, Kim KS, Kim SH. Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev. 2010;19(7):1035–1042. doi:10.1089/scd.2009.0453
   PubMed Web of Science ®Google Scholar
• Sun L, Fan X, Zhang L, et al. Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats. Int J Mol Med. 2014;34(4):987–996. doi:10.3892/ijmm.2014.1890
   PubMed Web of Science ®Google Scholar
• Yagi H, Parekkadan B, Suganuma K, et al. Long-term superior performance of a stem cell/hepatocyte device for the treatment of acute liver failure. Tissue Eng Part A. 2009;15(11):3377–3388. doi:10.1089/ten.TEA.2008.0681
   PubMed Web of Science ®Google Scholar
• Wang YH, Wu DB, Chen B, Chen EQ, Tang H. Progress in mesenchymal stem cell-based therapy for acute liver failure. Stem Cell Res Ther. 2018;9(1):227. doi:10.1186/s13287-018-0972-4
   PubMedGoogle Scholar
• Li T, Zhu J, Ma K, et al. Autologous bone marrow-derived mesenchymal stem cell transplantation promotes liver regeneration after portal vein embolization in cirrhotic rats. J Surg Res. 2013;184(2):1161–1173. doi:10.1016/j.jss.2013.04.054
   PubMed Web of Science ®Google Scholar
• Wang K, Chen X, Ren J. Autologous bone marrow stem cell transplantation in patients with liver failure: a meta-analytic review. Stem Cells Dev. 2015;24(2):147–159. doi:10.1089/scd.2014.0337
   PubMed Web of Science ®Google Scholar
• Rodriguez-Fuentes DE, Fernandez-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldana HA. Mesenchymal Stem Cells Current Clinical Applications: a Systematic Review. Arch Med Res. 2021;52(1):93–101. doi:10.1016/j.arcmed.2020.08.006
   PubMed Web of Science ®Google Scholar
• Cheleuitte D, Mizuno S, Glowacki J. In vitro secretion of cytokines by human bone marrow: effects of age and estrogen status. J Clin Endocrinol Metab. 1998;83(6):2043–2051. doi:10.1210/jcem.83.6.4848
   PubMed Web of Science ®Google Scholar
• Wei Y, Xie Z, Bi J, Zhu Z. Anti-inflammatory effects of bone marrow mesenchymal stem cells on mice with Alzheimer’s disease. Exp Ther Med. 2018;16(6):5015–5020. doi:10.3892/etm.2018.6857
   PubMed Web of Science ®Google Scholar
• Manshouri T, Estrov Z, Quintas-Cardama A, et al. Bone marrow stroma-secreted cytokines protect JAK2(V617F)-mutated cells from the effects of a JAK2 inhibitor. Cancer Res. 2011;71(11):3831–3840. doi:10.1158/0008-5472.CAN-10-4002
   PubMed Web of Science ®Google Scholar
• Lee JK, Schuchman EH, Jin HK, Bae JS. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid beta ameliorates Alzheimer’s disease in mice by recruiting bone marrow-induced microglia immune responses. Stem Cells. 2012;30(7):1544–1555. doi:10.1002/stem.1125
   PubMed Web of Science ®Google Scholar
• Gordon PM, Dias S, Williams DA. Cytokines secreted by bone marrow stromal cells protect c-KIT mutant AML cells from c-KIT inhibitor-induced apoptosis. Leukemia. 2014;28(11):2257–2260. doi:10.1038/leu.2014.212
   PubMed Web of Science ®Google Scholar
• Guo HD, Wang HJ, Tan YZ, Wu JH. Transplantation of marrow-derived cardiac stem cells carried in fibrin improves cardiac function after myocardial infarction. Tissue Eng Part A. 2011;17(1–2):45–58. doi:10.1089/ten.TEA.2010.0124
   PubMed Web of Science ®Google Scholar
• Zhou X, Xiu G, Zhu Y, et al. [Bone marrow mesenchymal stem cells modulated the inflammatory response by regulating the expression of IL-4 and RAGE products in the rats with MODS]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017;29(4):294–299. doi:10.3760/cma.j.issn.2095-4352.2017.04.002. Chinese.
   PubMedGoogle Scholar
• Chen S, Yi M, Zhou G, et al. Abdominal Aortic Transplantation of Bone Marrow Mesenchymal Stem Cells Regulates the Expression of Ciliary Neurotrophic Factor and Inflammatory Cytokines in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury. Med Sci Monit. 2019;25:1960–1969. doi:10.12659/MSM.912697
   PubMed Web of Science ®Google Scholar
• Park CW, Kim KS, Bae S, et al. Cytokine secretion profiling of human mesenchymal stem cells by antibody array. Int J Stem Cells. 2009;2(1):59–68. doi:10.15283/ijsc.2009.2.1.59
   PubMedGoogle Scholar
• Hwang JH, Lee MJ, Seok OS, et al. Cytokine expression in placenta-derived mesenchymal stem cells in patients with pre-eclampsia and normal pregnancies. Cytokine. 2010;49(1):95–101. doi:10.1016/j.cyto.2009.08.013
   PubMed Web of Science ®Google Scholar
• Madlambayan GJ, Butler JM, Hosaka K, et al. Bone marrow stem and progenitor cell contribution to neovasculogenesis is dependent on model system with SDF-1 as a permissive trigger. Blood. 2009;114(19):4310–4319. doi:10.1182/blood-2009-03-211342
   PubMed Web of Science ®Google Scholar
• Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS. Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer’s disease mice by modulation of immune responses. Stem Cells. 2010;28(2):329–343. doi:10.1002/stem.277
   PubMed Web of Science ®Google Scholar
• Norddahl GL, Wahlestedt M, Gisler S, Sigvardsson M, Bryder D. Reduced repression of cytokine signaling ameliorates age-induced decline in hematopoietic stem cell function. Aging Cell. 2012;11(6):1128–1131. doi:10.1111/j.1474-9726.2012.00863.x
   PubMed Web of Science ®Google Scholar
• Masiukiewicz US, Mitnick M, Gulanski BI, Insogna KL. Evidence that the IL-6/IL-6 soluble receptor cytokine system plays a role in the increased skeletal sensitivity to PTH in estrogen-deficient women. J Clin Endocrinol Metab. 2002;87(6):2892–2898. doi:10.1210/jcem.87.6.8577
   PubMed Web of Science ®Google Scholar
• Zhao R, Ying M, Gu S, et al. Cysteinyl Leukotriene Receptor 2 is Involved in Inflammation and Neuronal Damage by Mediating Microglia M1/M2 Polarization through NF-kappaB Pathway. Neuroscience. 2019;422:99–118. doi:10.1016/j.neuroscience.2019.10.048
   PubMed Web of Science ®Google Scholar
• Losurdo M, Pedrazzoli M, D’Agostino C, et al. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer’s disease. Stem Cells Transl Med. 2020;9(9):1068–1084. doi:10.1002/sctm.19-0327
   PubMed Web of Science ®Google Scholar
• Esmaeilzade B, Artimani T, Amiri I, et al. Dimethyloxalylglycine preconditioning enhances protective effects of bone marrow-derived mesenchymal stem cells in Abeta- induced Alzheimer disease. Physiol Behav. 2019;199:265–272. doi:10.1016/j.physbeh.2018.11.034
   PubMed Web of Science ®Google Scholar
• Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med. 2018;22(3):1428–1442. doi:10.1111/jcmm.13492
   PubMed Web of Science ®Google Scholar
• Costa MHG, Serra J, McDevitt TC, Cabral JMS, da Silva CL, Ferreira FC. Dimethyloxalylglycine, a small molecule, synergistically increases the homing and angiogenic properties of human mesenchymal stromal cells when cultured as 3-D spheroids. Biotechnol J. 2021;16:e2000389. doi:10.1002/biot.202000389
   PubMed Web of Science ®Google Scholar
• Han L, Zhou Y, Zhang R, et al. MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model. Front Neurosci. 2018;12:333. doi:10.3389/fnins.2018.00333
   PubMed Web of Science ®Google Scholar
• Park WS, Ahn SY, Sung SI, Ahn JY, Chang YS. Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders. Pediatr Res. 2018;83(1–2):214–222. doi:10.1038/pr.2017.249
   PubMed Web of Science ®Google Scholar
• Rahmat Z, Jose S, Ramasamy R, Vidyadaran S. Reciprocal interactions of mouse bone marrow-derived mesenchymal stem cells and BV2 microglia after lipopolysaccharide stimulation. Stem Cell Res Ther. 2013;4(1):12. doi:10.1186/scrt160
   PubMedGoogle Scholar
• Wen T, Meng H, Wang F, Chen Y, Sun T. Early immune response regulated by a bone marrow mesenchymal stem cell model of multiple trauma in rats. Immunotherapy. 2018;10(12):1053–1064. doi:10.2217/imt-2018-0010
   PubMed Web of Science ®Google Scholar
• Guk KD, Kuprash DV. [Interleukin-11, an IL-6 like cytokine]. Mol Biol Mosk. 2011;45(1):44–55.
   PubMed Web of Science ®Google Scholar
• Jiang Y, Gao H, Yuan H, et al. Amelioration of postoperative cognitive dysfunction in mice by mesenchymal stem cell-conditioned medium treatments is associated with reduced inflammation, oxidative stress and increased BDNF expression in brain tissues. Neurosci Lett. 2019;709:134372. doi:10.1016/j.neulet.2019.134372
   PubMed Web of Science ®Google Scholar
• Chen Y, Pan C, Xuan A, et al. Treatment Efficacy of NGF Nanoparticles Combining Neural Stem Cell Transplantation on Alzheimer’s Disease Model Rats. Med Sci Monit. 2015;21:3608–3615. doi:10.12659/msm.894567
   PubMed Web of Science ®Google Scholar
• Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. Br J Pharmacol. 2016;173(4):649–665. doi:10.1111/bph.13139
   PubMed Web of Science ®Google Scholar
• Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016;19(8):987–991. doi:10.1038/nn.4338
   PubMed Web of Science ®Google Scholar
• Noristani HEH, Perrin FE. Microglia Responses in Acute and Chronic Neurological Diseases: what Microglia-Specific Transcriptomic Studies Taught (and did Not Teach) Us. Front Aging Neurosci. 2017;9:227. doi:10.3389/fnagi.2017.00227
   PubMed Web of Science ®Google Scholar
• von Maydell D, Jorfi M. The interplay between microglial states and major risk factors in Alzheimer’s disease through the eyes of single-cell RNA-sequencing: beyond black and white. J Neurophysiol. 2019;122(4):1291–1296. doi:10.1152/jn.00395.2019
   PubMed Web of Science ®Google Scholar
• Zhu D, Yang N, Liu YY, Zheng J, Ji C, Zuo PP. M2 Macrophage Transplantation Ameliorates Cognitive Dysfunction in Amyloid-beta-Treated Rats Through Regulation of Microglial Polarization. J Alzheimers Dis. 2016;52(2):483–495. doi:10.3233/JAD-151090
   PubMed Web of Science ®Google Scholar
• Terashima T, Nakae Y, Katagi M, Okano J, Suzuki Y, Kojima H. Stem cell factor induces polarization of microglia to the neuroprotective phenotype in vitro. Heliyon. 2018;4(10):e00837. doi:10.1016/j.heliyon.2018.e00837
   PubMed Web of Science ®Google Scholar
• Oh S, Son M, Choi J, Lee S, Byun K. sRAGE prolonged stem cell survival and suppressed RAGE-related inflammatory cell and T lymphocyte accumulations in an Alzheimer’s disease model. Biochem Biophys Res Commun. 2018;495(1):807–813. doi:10.1016/j.bbrc.2017.11.035
   PubMed Web of Science ®Google Scholar
• Meda L, Cassatella MA, Szendrei GI, et al. Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature. 1995;374(6523):647–650. doi:10.1038/374647a0
   PubMed Web of Science ®Google Scholar
• von Saucken VE, Jay TR, Landreth GE. The effect of amyloid on microglia-neuron interactions before plaque onset occurs independently of TREM2 in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2020;145:105072. doi:10.1016/j.nbd.2020.105072
   PubMed Web of Science ®Google Scholar
• Casali BT, MacPherson KP, Reed-Geaghan EG, Landreth GE. Microglia depletion rapidly and reversibly alters amyloid pathology by modification of plaque compaction and morphologies. Neurobiol Dis. 2020;142:104956. doi:10.1016/j.nbd.2020.104956
   PubMed Web of Science ®Google Scholar
• Lee JK, Jin HK, Bae JS. Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neurosci Lett. 2009;450(2):136–141. doi:10.1016/j.neulet.2008.11.059
   PubMed Web of Science ®Google Scholar
• Kim M, Kim KH, Song SU, et al. Transplantation of human bone marrow-derived clonal mesenchymal stem cells reduces fibrotic scar formation in a rat spinal cord injury model. J Tissue Eng Regen Med. 2018;12(2):e1034–e1045. doi:10.1002/term.2425
   PubMed Web of Science ®Google Scholar
• Lively S, Schlichter LC. Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNgamma+TNFalpha) and Reprogramming by Resolving Cytokines (IL-4, IL-10). Front Cell Neurosci. 2018;12:215. doi:10.3389/fncel.2018.00215
   PubMed Web of Science ®Google Scholar
• Szczepanik AM, Funes S, Petko W, Ringheim GE. IL-4, IL-10 and IL-13 modulate A beta(1–42)-induced cytokine and chemokine production in primary murine microglia and a human monocyte cell line. J Neuroimmunol. 2001;113(1):49–62. doi:10.1016/s0165-5728(00)00404-5
   PubMed Web of Science ®Google Scholar
• Yu S, Hei Y, Liu W. Upregulation of seladin-1 and nestin expression in bone marrow mesenchymal stem cell transplantation via the ERK1/2 and PI3K/Akt signaling pathways in an Alzheimer’s disease model. Oncol Lett. 2018;15(5):7443–7449. doi:10.3892/ol.2017.7543
   PubMed Web of Science ®Google Scholar
• Luciani P, Deledda C, Rosati F, et al. Seladin-1 is a fundamental mediator of the neuroprotective effects of estrogen in human neuroblast long-term cell cultures. Endocrinology. 2008;149(9):4256–4266. doi:10.1210/en.2007-1795
   PubMed Web of Science ®Google Scholar
• Schafer 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):40–48. doi:10.1016/j.jneuroim.2012.04.018
   PubMed Web of Science ®Google Scholar
• Duarte RF, Frank DA. SCF and G-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways. Blood. 2000;96(10):3422–3430. doi:10.1182/blood.V96.10.3422
   PubMed Web of Science ®Google Scholar
• Prakash A, Medhi B, Chopra K. Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-beta induced experimental model of Alzheimer’s disease. Pharmacol Biochem Behav. 2013;110:46–57. doi:10.1016/j.pbb.2013.05.015
   PubMed Web of Science ®Google Scholar
• Tsai KJ, Tsai YC, Shen CK. G-CSF rescues the memory impairment of animal models of Alzheimer’s disease. J Exp Med. 2007;204(6):1273–1280. doi:10.1084/jem.20062481
   PubMed Web of Science ®Google Scholar
• Cao C, Wang L, Lin X, et al. Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice. J Alzheimers Dis. 2011;25(2):323–335. doi:10.3233/JAD-2011-110110
   PubMed Web of Science ®Google Scholar
• Ji J, Xue TF, Guo XD, et al. Antagonizing peroxisome proliferator-activated receptor gamma facilitates M1-to-M2 shift of microglia by enhancing autophagy via the LKB1-AMPK signaling pathway. Aging Cell. 2018;17(4):e12774. doi:10.1111/acel.12774
   PubMed Web of Science ®Google Scholar
• Cui GH, Wu J, Mou FF, et al. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J. 2018;32(2):654–668. doi:10.1096/fj.201700600R
   PubMed Web of Science ®Google Scholar
• Kempuraj D, Thangavel R, Natteru PA, et al. Neuroinflammation Induces Neurodegeneration. J Neurol Neurosurg Spine. 2016;1(1):587.
   Google Scholar
• Liu W, Rong Y, Wang J, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization. J Neuroinflammation. 2020;17(1):47. doi:10.1186/s12974-020-1726-7
   PubMed Web of Science ®Google Scholar
• Zhong Z, Chen A, Fa Z, et al. Adipose-Derived Stem Cells Modulate BV2 Microglial M1/M2 Polarization by Producing GDNF. Stem Cells Dev. 2020;29(11):714–727. doi:10.1089/scd.2019.0235
   PubMed Web of Science ®Google Scholar
• Sackmann V, Ansell A, Sackmann C, et al. Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells. Neurobiol Aging. 2017;60:173–182. doi:10.1016/j.neurobiolaging.2017.08.022
   PubMed Web of Science ®Google Scholar
• Boyette LB, Macedo C, Hadi K, et al. Phenotype, function, and differentiation potential of human monocyte subsets. PLoS One. 2017;12(4):e0176460. doi:10.1371/journal.pone.0176460
   PubMed Web of Science ®Google Scholar
• Choudhury ME, Sugimoto K, Kubo M, et al. A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats. Brain Behav. 2011;1(1):26–43. doi:10.1002/brb3.11
   PubMed Web of Science ®Google Scholar
• Safar MM, Arab HH, Rizk SM, El-Maraghy SA. Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations. Mol Neurobiol. 2016;53(3):1403–1418. doi:10.1007/s12035-014-9051-8
   PubMed Web of Science ®Google Scholar
• Nakano M, Kubota K, Kobayashi E, et al. 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. doi:10.1038/s41598-020-67460-1
   PubMed Web of Science ®Google Scholar
• Li S, Guan H, Zhang Y, et al. Bone marrow mesenchymal stem cells promote remyelination in spinal cord by driving oligodendrocyte progenitor cell differentiation via TNFalpha/RelB-Hes1 pathway: a rat model study of 2,5-hexanedione-induced neurotoxicity. Stem Cell Res Ther. 2021;12(1):436. doi:10.1186/s13287-021-02518-z
   PubMed Web of Science ®Google Scholar
• Monsonego A, Imitola J, Zota V, Oida T, Weiner HL. Microglia-mediated nitric oxide cytotoxicity of T cells following amyloid beta-peptide presentation to Th1 cells. J Immunol. 2003;171(5):2216–2224. doi:10.4049/jimmunol.171.5.2216
   PubMed Web of Science ®Google Scholar
• Zarif H, Hosseiny S, Paquet A, et al. CD4(+) T Cells Have a Permissive Effect on Enriched Environment-Induced Hippocampus Synaptic Plasticity. Front Synaptic Neurosci. 2018;10:14. doi:10.3389/fnsyn.2018.00014
   PubMed Web of Science ®Google Scholar
• Yamanaka M, Ishikawa T, Griep A, Axt D, Kummer MP, Heneka MT. PPARgamma/RXRalpha-induced and CD36-mediated microglial amyloid-beta phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J Neurosci. 2012;32(48):17321–17331. doi:10.1523/JNEUROSCI.1569-12.2012
   PubMed Web of Science ®Google Scholar
• Boche D, Nicoll JAR. Invited Review - Understanding cause and effect in Alzheimer’s pathophysiology: implications for clinical trials. Neuropathol Appl Neurobiol. 2020;46(7):623–640. doi:10.1111/nan.12642
   PubMed Web of Science ®Google Scholar
• Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88(4):640–651. doi:10.1016/j.bcp.2013.12.024
   PubMed Web of Science ®Google Scholar
• Kang HJ, Yoon WJ, Moon GJ, et al. Caspase-3-mediated cleavage of PHF-1 tau during apoptosis irrespective of excitotoxicity and oxidative stress: an implication to Alzheimer’s disease. Neurobiol Dis. 2005;18(3):450–458. doi:10.1016/j.nbd.2004.12.004
   PubMed Web of Science ®Google Scholar
• Mo SJ, Zhong Q, Zhou YF, Deng DB, Zhang XQ. Bone marrow-derived mesenchymal stem cells prevent the apoptosis of neuron-like PC12 cells via erythropoietin expression. Neurosci Lett. 2012;522(2):92–97. doi:10.1016/j.neulet.2012.06.002
   PubMed Web of Science ®Google Scholar
• Okazaki T, Magaki T, Takeda M, et al. Intravenous administration of bone marrow stromal cells increases survivin and Bcl-2 protein expression and improves sensorimotor function following ischemia in rats. Neurosci Lett. 2008;430(2):109–114. doi:10.1016/j.neulet.2007.10.046
   PubMed Web of Science ®Google Scholar
• Liu L, Cao JX, Sun B, et al. Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via upregulation of phosphatidylinositol-3-kinase/Akt and modulation of extracellular signal-regulated kinase 1/2 activation in PC12 cells and neurons. Neuroscience. 2010;167(4):1115–1124. doi:10.1016/j.neuroscience.2010.01.057
   PubMed Web of Science ®Google Scholar
• Chen J, Li Y, Zhang R, et al. Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis. Brain Res. 2004;1005(1–2):21–28. doi:10.1016/j.brainres.2003.11.080
   PubMed Web of Science ®Google Scholar
• Lee JK, Jin HK, Bae JS. Bone marrow-derived mesenchymal stem cells attenuate amyloid beta-induced memory impairment and apoptosis by inhibiting neuronal cell death. Curr Alzheimer Res. 2010;7(6):540–548. doi:10.2174/156720510792231739
   PubMed Web of Science ®Google Scholar
• Lee JK, Jin HK, Bae JS. Bone marrow-derived mesenchymal stem cells attenuate amyloid beta-induced memory impairment and apoptosis by inhibiting neuronal cell death. Curr Alzheimer Res. 2010;7(6):540–548.
   PubMed Web of Science ®Google Scholar
• Marei HE, Farag A, Althani A, et al. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer’s disease rat model. J Cell Physiol. 2015;230(1):116–130. doi:10.1002/jcp.24688
   PubMed Web of Science ®Google Scholar
• Bae JS, Han HS, Youn DH, et al. Bone marrow-derived mesenchymal stem cells promote neuronal networks with functional synaptic transmission after transplantation into mice with neurodegeneration. Stem Cells. 2007;25(5):1307–1316. doi:10.1634/stemcells.2006-0561
   PubMed Web of Science ®Google Scholar
• Harrell CR, Volarevic A, Djonov V, Volarevic V. Mesenchymal Stem Cell-Derived Exosomes as New Remedy for the Treatment of Neurocognitive Disorders. Int J Mol Sci. 2021;22(3):58. doi:10.3390/ijms22031433
   Web of Science ®Google Scholar