Abstract
Alzheimer’s disease (AD) is one of the most common causes of dementia. Despite several decades of research in AD, there is no standard disease- modifying therapy available and currentlyapproved drugs provide only symptomatic relief. Stem cells hold immense potential to regenerate damaged tissues and are currently tested in some brain-related disorders, such as AD, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). We review stem cell transplantation studies using preclinical and clinical tools. We describe different sources of stem cells used in various animal models and explaining the putative molecular mechanisms that can rescue neurodegenerative disorders. The clinical studies suggest safety, efficacy and translational potential of stem cell therapy. The therapeutic outcome of stem cell transplantation has been promising in many studies, but no unifying hypothesis can convincingly explain the underlying mechanism. Some studies have reported paracrine effects exerted by these stem cells via the release of neurotrophic factors, while other studies describe the immunomodulatory effects exerted by the transplanted cells. There are also reports which indicate that stem cell transplantation might result in endogenous cell proliferation or replacement of diseased cells. In animal models of AD, stem cell transplantation is also believed to increase expression of synaptic proteins.
Keywords: Aging, dementia, differentiation, neurodegeneration, synaptogenesis, proliferation, therapeutics, transplantation.
[1]
Martin A. Maëlenn Guerchet, Gemma-Claire Ali, Yu-Tzu Wu, Matthew. World Alzheimer Report 2015. Alzheimer’s Dis Int (2015).
[3]
ARSI. Alzheimer's and Related Disorders Society of India
(ARDSI) (2010). Available at. ardsi.org
[4]
Graeber MB, Kosel S, Egensperger R, Banati RB, Muller U, Bise K, et al. Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis. Neurogenetics 1(1): 73-80. (1997)
[5]
Cummings JL, Back C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer’s disease. Am J Geriatr Psychiatry 6(2)(Suppl. 1): S64-78. (1998)
[6]
Soto C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 4(1): 49-60. (2003)
[7]
Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054): 184-5. (1992)
[8]
Altman J. Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec 145: 573-91. (1963)
[9]
Si YC, Li Q, Xie CE, Niu X, Xia XH, Yu CY. Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells. Chin Med 9(1): 13. (2014)
[10]
Saraf MK, Prabhakar S, Khanduja KL, Anand A. Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice. Evid Based Complement Alternat Med 2011236186 (2011)
[11]
Prabhakar S, Saraf MK, Banik A, Anand A. Bacopa monniera selectively attenuates suppressed Superoxide dismutase activity in Diazepam induced amnesic mice. Ann Neurosci 18(1): 8-13. (2011)
[12]
Saraf MK, Prabhakar S, Anand A. Neuroprotective effect of Bacopa monniera on ischemia induced brain injury. Pharmacol Biochem Behav 97(2): 192-7. (2010)
[13]
Singh T, Prabhakar S, Gupta A, Anand A. Recruitment of stem cells into the injured retina after laser injury. Stem Cells Dev 21(3): 448-54. (2012)
[14]
Muthaian R, Minhas G, Anand A. Pathophysiology of stroke and stroke-induced retinal ischemia: emerging role of stem cells. J Cell Physiol 227(3): 1269-79. (2012)
[15]
Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Muller FJ, Loring JF, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA 106(32): 13594-9. (2009)
[16]
Wilcock GK, Esiri MM. Plaques, tangles and dementia. A quantitative study. J Neurol Sci 56(2-3): 343-56. (1982)
[17]
Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286(5440): 735-41. (1999)
[18]
Bie B, Wu J, Yang H, Xu JJ, Brown DL, Naguib M. Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency. Nat Neurosci 17(2): 223-31. (2014)
[19]
Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2(8000): 1403. (1976)
[20]
Thies W, Bleiler L. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement 9(2): 208-45. (2013)
[21]
Tai LM, Ghura S, Koster KP, Liakaite V, Maienschein-Cline M, Kanabar P, et al. APOE-modulated Abeta-induced neuroinflammation in Alzheimer’s disease: current landscape, novel data, and future perspective. J Neurochem 133(4): 465-88. (2015)
[22]
Wisniewski T, Frangione B. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett 135(2): 235-8. (1992)
[23]
Lahiri DK, Maloney B, Basha MR, Ge YW, Zawia NH. How and when environmental agents and dietary factors affect the course of Alzheimer’s disease: the “LEARn” model (latent early-life associated regulation) may explain the triggering of AD. Curr Alzheimer Res 4(2): 219-28. (2007)
[24]
Banik A, Prabhakar S, Kalra J, Anand A. An enriched population of CD45, CD34 and CD117 stem cells in human umbilical cord blood for potential therapeutic regenerative strategies. Curr Neurovasc Res 11(4): 312-20. (2014)
[25]
Jindal N, Minhas G, Prabhakar S, Anand A. Characterization of Lin-ve CD34 and CD117 cell population reveals an increased expression in bone marrow derived stem cells. Curr Neurovasc Res 11(1): 68-74. (2014)
[26]
Abburi C, Prabhakar S, Kalra J, Huria A, Anand A. Vascular endothelial growth factor (VEGF) induced proliferation of human fetal derived ciliary epithelium stem cells is mediated by jagged-N cadherin pathway. Curr Neurovasc Res 10(2): 93-102. (2013)
[27]
Abburi C, Anand A. Ciliary epithelium: an underevaluated target for therapeutic regeneration. Crit Rev Eukaryot Gene Expr 22(2): 87-95. (2012)
[28]
Ray B, Chopra N, Long JM, Lahiri DK. Human primary mixed brain cultures: preparation, long-term maintenance, characterization and application to neuroscience research. Mol Brain 7(1): 63. (2014)
[29]
Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T, et al. Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet 20(23): 4530-9. (2011)
[30]
Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, et al. Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12(4): 487-96. (2013)
[31]
Long JM, Ray B, Lahiri DK. MicroRNA-339-5p down-regulates protein expression of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects. J Biol Chem 289(8): 5184-98. (2014)
[32]
Cure S, Abrams K, Belger M, Dell’agnello G, Happich M. Systematic literature review and meta-analysis of diagnostic test accuracy in Alzheimer’s disease and other dementia using autopsy as standard of truth. J Alzheimers Dis 42(1): 169-82. (2014)
[33]
Anand A, Banik A, Thakur K, Masters CL. The animal models of dementia and Alzheimer’s disease for pre-clinical testing and clinical translation. Curr Alzheimer Res 9(9): 1010-29. (2012)
[34]
Banik A, Anand APD. Preclinical non-human models to combat dementia. Ann Neurosci 20(1): 24-9. (2013)
[35]
Ernfors P, Wetmore C, Olson L, Persson H. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron 5(4): 511-26. (1990)
[36]
Prakash A, Kumar A. Role of nuclear receptor on regulation of BDNF and neuroinflammation in hippocampus of beta-amyloid animal model of Alzheimer’s disease. Neurotox Res 25(4): 335-47. (2014)
[37]
Seaberg RM, van der Kooy D. Stem and progenitor cells: the premature desertion of rigorous definitions. Trends Neurosci 26(3): 125-31. (2003)
[38]
Tang J, Xu H, Fan X, Li D, Rancourt D, Zhou G, et al. Embryonic stem cell-derived neural precursor cells improve memory dysfunction in Abeta(1-40) injured rats. Neurosci Res 62(2): 86-96. (2008)
[39]
Banik A, Prabhakar S, Kalra J, Anand A. Effect of human umbilical cord blood derived lineage negative stem cells transplanted in amyloid-β induced cognitive impaired mice. Behav Brain Res 15(291): 46-59. (2015)
[40]
Blurton-Jones M, Spencer B, Michael S, Castello NA, Agazaryan AA, Davis JL, et al. Neural stem cells genetically-modified to express neprilysin reduce pathology in Alzheimer transgenic models. Stem Cell Res Ther 5(2): 46. (2014)
[41]
ON K. Oral presentation of Peri-hippocampal stem cell transplantation
rescues cognitive decline in Alzheimer's disease Boston, Massachusetts:
Congress of Neurological Surgeons Annual Meeting. (2014)
[42]
Jin K, Xie L, Mao X, Greenberg MB, Moore A, Peng B, et al. Effect of human neural precursor cell transplantation on endogenous neurogenesis after focal cerebral ischemia in the rat. Brain Res 1374: 56-62. (2011)
[43]
Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, Oh W, et al. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer’s disease mouse model through modulation of neuroinflammation. Neurobiol Aging 33(3): 588-602. (2012)
[44]
Garcia KO, Ornellas FL, Martin PK, Patti CL, Mello LE, Frussa-Filho R, et al. Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer’s disease. Front Aging Neurosci 6: 30. (2014)
[45]
Cherry JD, Olschowka JA, O’Banion MK. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflam 11: 98. (2014)
[46]
Yang H, Xie Z, Wei L, Yang H, Yang S, Zhu Z, et al. Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AbetaPP/PS1 transgenic mouse model. Stem Cell Res Ther 4(4): 76. (2013)
[47]
Salem AM, Ahmed HH, Atta HM, Ghazy MA, Aglan HA. Potential of bone marrow mesenchymal stem cells in management of Alzheimer’s disease in female rats. Cell Biol Int 38(12): 1367-83. (2014)
[48]
Oh SH, Kim HN, Park HJ, Shin JY, Lee PH. Mesenchymal stem cells increase hippocampal neurogenesis and neuronal differentiation by enhancing the Wnt signaling pathway in Alzheimer’s disease model. Cell Transplant 24(6): 1097-109. (2014)
[49]
Zhang W, Wang GM, Wang PJ, Zhang Q, Sha SH. Effects of neural stem cells on synaptic proteins and memory in a mouse model of Alzheimer’s disease. J Neurosci Res 92(2): 185-94. (2014)
[50]
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 110: 46-57. (2013)
[51]
Shetty P, Thakur AM, Viswanathan C. Dopaminergic cells, derived from a high efficiency differentiation protocol from umbilical cord derived mesenchymal stem cells, alleviate symptoms in a Parkinson’s disease rodent model. Cell Biol Int 37(2): 167-80. (2013)
[52]
Chen S, Lewallen M, Xie T. Adhesion in the stem cell niche: biological roles and regulation. Development 140(2): 255-65. (2013)
[53]
Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, et al. Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition. Stem Cell Reports 4(3): 360-73. (2015)
[54]
Dlouhy BJ, Awe O, Rao RC, Kirby PA, Hitchon PW. Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient: Case report. J Neurosurg Spine 21(4): 618-22. (2014)
[55]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4): 663-76. (2006)
[56]
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26(1): 101-6. (2008)
[57]
Jarocha D, Milczarek O, Kawecki Z, Wendrychowicz A, Kwiatkowski S, Majka M. Preliminary study of autologous bone marrow nucleated cells transplantation in children with spinal cord injury. Stem Cells Transl Med 3(3): 395-404. (2014)
[58]
Mazzini L, Gelati M, Profico DC, Sgaravizzi G, Projetti Pensi M, Muzi G, et al. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med 13(1): 17. (2015)
[59]
Song JH, Yu JT, Tan L. Brain-derived neurotrophic factor in alzheimer’s disease: risk, mechanisms, and therapy. Mol Neurobiol 52(3): 1477-93. (2014)
[60]
Dominguez G, Dagnas M, Decorte L, Vandesquille M, Belzung C, Beracochea D, et al. Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure. Brain Struct Funct 221(2): 865-77. (2014)
[61]
Saraf MK, Anand A, Prabhakar S. Scopolamine induced amnesia is reversed by Bacopa monniera through participation of kinase-CREB pathway. Neurochem Res 35(2): 279-87. (2010)
[62]
Hota SK, Barhwal K, Baitharu I, Prasad D, Singh SB, Ilavazhagan G. Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment. Neurobiol Dis 34(1): 23-39. (2009)
[63]
Tota S, Goel R, Pachauri SD, Rajasekar N, Najmi AK, Hanif K, et al. Effect of angiotensin II on spatial memory, cerebral blood flow, cholinergic neurotransmission, and brain derived neurotrophic factor in rats. Psychopharmacology (Berl) 226(2): 357-69. (2013)
[64]
Sharma N, Jadhav SP, Bapat SA. CREBBP re-arrangements affect protein function and lead to aberrant neuronal differentiation. Differentiation 79(4-5): 218-31. (2010)
[65]
Raheja G, Gill KD. Altered cholinergic metabolism and muscarinic receptor linked second messenger pathways after chronic exposure to dichlorvos in rat brain. Toxicol Ind Health 23(1): 25-37. (2007)
[66]
Verma SK, Raheja G, Gill KD. Role of muscarinic signal transduction and CREB phosphorylation in dichlorvos-induced memory deficits in rats: an acetylcholine independent mechanism. Toxicology 256(3): 175-82. (2009)
[67]
Yasuhara T, Hara K, Maki M, Xu L, Yu G, Ali MM, et al. Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts. J Cell Mol Med 14(4): 914-21. (2010)
[68]
Fumagalli F, Racagni G, Riva MA. The expanding role of BDNF: a therapeutic target for Alzheimer’s disease? Pharmacogenomics J 6(1): 8-15. (2006)
[69]
Siegel GJ, Chauhan NB. Neurotrophic factors in Alzheimer’s and Parkinson’s disease brain. Brain Res Brain Res Rev 33(2-3): 199-227. (2000)
[70]
Fahnestock M, Garzon D, Holsinger RM, Michalski B. Neurotrophic factors and Alzheimer’s disease: are we focusing on the wrong molecule? J Neural Transm Suppl (62): 241-52. (2002)
[71]
Peng S, Wuu J, Mufson EJ, Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem 93(6): 1412-21. (2005)
[72]
Michalski B, Fahnestock M. Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer’s disease. Brain Res Mol Brain Res 111(1-2): 148-54. (2003)
[73]
Holsinger RM, Schnarr J, Henry P, Castelo VT, Fahnestock M. Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease. Brain Res Mol Brain Res 76(2): 347-54. (2000)
[74]
Kitiyanant N, Kitiyanant Y, Svendsen CN, Thangnipon W. BDNF-, IGF-1- and GDNF-secreting human neural progenitor cells rescue amyloid beta-induced toxicity in cultured rat septal neurons. Neurochem Res 37(1): 143-52. (2012)
[75]
Arancibia S, Silhol M, Mouliere F, Meffre J, Hollinger I, Maurice T, et al. Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis 31(3): 316-26. (2008)
[76]
Holback S, Adlerz L, Iverfeldt K. Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells. J Neurochem 95(4): 1059-68. (2005)
[77]
Tong L, Balazs R, Thornton PL, Cotman CW. Beta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. J Neurosci 24(30): 6799-809. (2004)
[78]
Zeng Y, Zhao D, Xie CW. Neurotrophins enhance CaMKII activity and rescue amyloid-beta-induced deficits in hippocampal synaptic plasticity. J Alzheimers Dis 21(3): 823-31. (2010)
[79]
Li N, Liu GT. The novel squamosamide derivative FLZ enhances BDNF/TrkB/CREB signaling and inhibits neuronal apoptosis in APP/PS1 mice. Acta Pharmacol Sin 31(3): 265-72. (2010)
[80]
Lee Y, Kim J, Jang S, Oh S. Administration of phytoceramide enhances memory and upregulates the expression of pCREB and BDNF in hippocampus of mice. Biomol Ther (Seoul) 21(3): 229-33. (2013)
[81]
M F The effects of CREB-mediated BDNF expression on memory-
and anxiety-related behaviours in the adult mouse MSc dissertation.
Canada: Institute of Medical Science University of Toronto. 2012.
[82]
Silva AJ, Kogan JH, Frankland PW, Kida S. CREB and memory. Annu Rev Neurosci 21: 127-48. (1998)
[83]
Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23: 649-711. (2000)
[84]
Jensen KF, Ohmstede CA, Fisher RS, Sahyoun N. Nuclear and axonal localization of Ca2+/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex. Proc Natl Acad Sci USA 88(7): 2850-3. (1991)
[85]
Nakamura Y, Okuno S, Sato F, Fujisawa H. An immunohistochemical study of Ca2+/calmodulin-dependent protein kinase IV in the rat central nervous system: light and electron microscopic observations. Neuroscience 68(1): 181-94. (1995)
[86]
Matthews RP, Guthrie CR, Wailes LM, Zhao X, Means AR, McKnight GS. Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol 14(9): 6107-16. (1994)
[87]
Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365(6449): 855-9. (1993)
[88]
Bito H, Deisseroth K, Tsien RW. CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression. Cell 87(7): 1203-14. (1996)
[98]
Suzuki A, Fukushima H, Mukawa T, Toyoda H, Wu LJ, Zhao MG, et al. Upregulation of CREB-mediated transcription enhances both short- and long-term memory. J Neurosci 31(24): 8786-802. (2011)
[90]
Venkataramana NK, Kumar SK, Balaraju S, Radhakrishnan RC, Bansal A, Dixit A, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res 155(2): 62-70. (2010)
[91]
Yin F, Tian ZM, Liu S, Zhao QJ, Wang RM, Shen L, et al. Transplantation of human retinal pigment epithelium cells in the treatment for Parkinson disease. CNS Neurosci Ther 18(12): 1012-20. (2012)
[92]
Mancias-Guerra C, Marroquin-Escamilla AR, Gonzalez-Llano O, Villarreal-Martinez L, Jaime-Perez JC, Garcia-Rodriguez F, et al. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial. Cytotherapy 16(6): 810-20. (2014)
[93]
http://clinicaltrials.gov/ct2/show/NCT01297218The safety and the
efficacy evaluation of NEUROSTEM®-AD in patients with Alzheimer's
disease. ClinicalTrialsgov Identifier NCT01297218.
[94]
https://clinicaltrials.gov/ct2/show/NCT01547689Safety and efficiency of umbilical cord-derived mesenchymal stem cells(UCMSC) in patients with Alzheimer's disease (SEMAD). ClinicalTrialsgov Identifier NCT01547689May. (2014)
[95]
https://clinicaltrials.gov/ct2/show/NCT02054208Safety and exploratory
efficacy study of NEUROSTEM® versus placebo in patients
with Alzheimer's disease. clinicaltrialsgov identifier nct02054208February. (2014)
[96]
Banik A, Brown RE, Bamburg J, Lahiri DK, Khurana D, Friedland RP, et al. Translation of pre-clinical studies into successful clinical trials for Alzheimer’s disease: What are the roadblocks and how can they be overcome? J Alzheimers Dis 47(4): 815-43. (2015)
[97]
Zhang R, Liu Y, Yan K, Chen L, Chen XR, Li P, et al. Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J Neuroinflammation 10(1): 106. (2013)
[98]
Wen SR, Qi HP, Ren YJ, Liu GJ, Gong FC, Zhong H, et al. Expression of deltaNp73 in hippocampus of APP/PS1 transgenic mice following GFP-BMSCs transplantation. Neurol Res 33(10): 1109-14. (2011)
[99]
Marei HE, Farag A, Althani A, Afifi N, A AE, Lashen S, et al. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer’s disease rat model. J Cell Physiol 230(7): 1614-29. (2014)
[100]
Zhang W, Gu GJ, Shen X, Zhang Q, Wang GM, Wang PJ. Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer’s disease-like pathology. Neurobiol Aging 36(3): 1282-92. (2015)
[101]
Yun HM, Kim HS, Park KR, Shin JM, Kang AR, il Lee K, et al. Placenta-derived mesenchymal stem cells improve memory dysfunction in an Abeta1-42-infused mouse model of Alzheimer’s disease. Cell Death Dis 4e958 (2013)
[102]
Shin JY, Park HJ, Kim HN, Oh SH, Bae JS, Ha HJ, et al. Mesenchymal stem cells enhance autophagy and increase beta-amyloid clearance in Alzheimer disease models. Autophagy 10(1): 32-44. (2014)
[103]
Yang H, Yang H, Xie Z, Wei L, Bi J. Systemic transplantation of human umbilical cord derived mesenchymal stem cells-educated T regulatory cells improved the impaired cognition in AbetaPPswe/PS1dE9 transgenic mice. PLoS One 8(7)e69129 (2013)
[104]
Kim KS, Kim HS, Park JM, Kim HW, Park MK, Lee HS, et al. Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer’s disease model. Neurobiol Aging 34(10): 2408-20. (2013)
[105]
Kim S, Chang KA, Kim J, Park HG, Ra JC, Kim HS, et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer’s disease mice. PLoS One 7(9)e45757 (2012)
[106]
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 10(5): 524-31. (2013)
[107]
Kim JY, Kim DH, Kim JH, Lee D, Jeon HB, Kwon SJ, et al. Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-beta plaques. Cell Death Differ 19(4): 680-91. (2012)
[108]
Esmaeilzade B, Nobakht M, Joghataei MT, Rahbar Roshandel N, Rasouli H, Samadi Kuchaksaraei A, et al. Delivery of epidermal neural crest stem cells (EPI-NCSC) to hippocamp in Alzheimer’s disease rat model. Iran Biomed J 16(1): 1-9. (2012)
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