Advertisement

Stem Cells in Alzheimer’s Disease: Current Standing and Future Challenges

  • Haitham Salem
  • Gabriela D. Colpo
  • Antonio L. Teixeira
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1079)

Abstract

To date, there is no definitive treatment for Alzheimer’s disease (AD). The realm of stem cells is very promising in regenerative medicine, particularly for neurodegenerative diseases. Various types of stem cells have been used in preclinical/clinical trials for AD aiming the development of an elusive disease modifying therapy. Over the last decade, much knowledge has been gained in this field regarding types of cells, routes and timing of administration, and outcomes of stem cells-based strategies for AD. In this chapter, we will trace the state of art and the challenges facing the use of stem cells in AD.

Keywords

Alzheimer’s disease Mesenchymal stem cells Neuroinflammation Neuronal stem cells 

Abbreviation

AD

Alzheimer’s disease

ADSCs

Adipose tissue derived stem cells

Amyloid-beta plaques

BDNF

Brain derived neurotropic factor

Epi-NCSCs

Epidermal neural crest derived stem cells

ESCs

Embryonic stem cells

HUCBCs

Human umbilical cord blood cells

IA

Intra-arterial

IC

Intracerebral

IL-10

Interleukin-10

IL-1β

Interleukin-1 beta

IL-4

Interleukin-4

iPSCs

Induced pluripotent stem cells

IV

Intravenous

MRI

Magnetic resonance imaging

MSCs

Mesenchymal stem cells

NGF

Nerve growth factor

NIRFI

Near-infrared fluorescence imaging

NPCs

Neuronal precursor cells

NSCs

Neuronal stem cells

SPECT

Single-photon emission computed tomography

TNF-α

Tumor necrosis factor alpha

Notes

Acknowledgements

The Neuropsychiatry Program/Immuno-Psychiatry Lab is funded by a grant from the Department of Psychiatry and Behavioral Sciences, UT Health Houston.

References

  1. Ager RR, Davis JL, Agazaryan A, Benavente F, Poon WW, LaFerla FM, Blurton-Jones M (2015) Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer’s disease and neuronal loss. Hippocampus 25:813–826CrossRefPubMedPubMedCentralGoogle Scholar
  2. Anghileri E, Marconi S, Pignatelli A, Cifelli P, Galie M, Sbarbati A, Krampera M, Belluzzi O, Bonetti B (2008) Neuronal differentiation potential of human adiposederived mesenchymal stem cells. Stem Cells Dev 17:909–916CrossRefPubMedGoogle Scholar
  3. Bae JS, Jin HK, Lee JK, Richardson JC, Carter JE (2013) Bone marrow-derived mesenchymal stem cells contribute to the reduction of amyloid-β deposits and the improvement of synaptic transmission in a mouse model of pre-dementia Alzheimer’s disease. Curr Alzheimer Res 10:524–531CrossRefPubMedGoogle Scholar
  4. Barkholt L, Flory E, Jekerle V, Lucas-Samuel S, Ahnert P, Bisset L, Buscher D, Fibbe W, Foussat A, Kwa M, Lantz O, Maciulaitis R, Palomaki T, Schneider CK, Sensebe L, Tachdjian G, Tarte K, Tosca L, Salmikangas P, Capilla-Gonzalez V, Lavell E, Quinones-Hinojosa A, Guerrero-Cazares H (2015) Regulation of subventricular zone-derived cells migration in the adult brain. Adv Exp Med Biol 853:1–21CrossRefGoogle Scholar
  5. Bash D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8:301–316CrossRefGoogle Scholar
  6. Birch AM, Katsouri L, Sastre M (2014) Modulation of inflammation in transgenic models of Alzheimer’s disease. Neuroinflammation 11:25CrossRefGoogle Scholar
  7. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Muller FJ, Loring JF, Yamasaki TR, Poon WW, Green KN, LaFerla FM (2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A 106:13594–13599CrossRefPubMedPubMedCentralGoogle Scholar
  8. Burns A, Iliffe S (2009) Alzheimer’s disease. BMJ 338:b158CrossRefGoogle Scholar
  9. Capilla-Gonzalez V, Herranz-Perez V, Garcia-Verdugo JM (2015) The aged brain: genesis and fate of residual progenitor cells in the subventricular zone. Front Cell Neurosci 9:365CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cassar P, Blundell R (2016) The use of umbilical stem cells. Open J Pathol 6:41–56CrossRefGoogle Scholar
  11. Cerri S, Greco R, Levandis G, Ghezzi C, Mangione AS, Fuzzati-Armentero MT, Bonizzi A, Avanzini MA, Maccario R, Blandini F (2015) Intracarotid infusion of mesenchymal stem cells in an animal model of Parkinson’s disease, focusing on cell distribution and neuroprotective and behavioral effects. Stem Cells Transl Med 4:1073–1085CrossRefPubMedPubMedCentralGoogle Scholar
  12. Chen X, Wang S, Cao W (2017) Mesenchymal stem cell medicated immunomodulation in cell therapy of neurodegenerative diseases. Cell Immunol. pii: S0008–8749(17)30101–6. doi:  https://doi.org/10.1016/j.cellimm.2017.06.006. [Epub ahead of print]
  13. Cheng SH, Yu D, Tsai HM, Morshed RA, Kanojia D, Lo LW, Leoni L, Govind Y, Zhang L, Aboody KS, Lesniak MS, Chen CT, Balyasnikova IV (2015) Dynamic in vivo SPECT imaging of neural stem cells functionalized with radiolabeled nanoparticles for tracking of glioblastoma. J Nucl Med 57:279–284CrossRefPubMedPubMedCentralGoogle Scholar
  14. Chung J, Yang PC (2010) Molecular imaging of stem cell transplantation in myocardial disease. Curr Cardiovasc Imaging Rep 3:106–112CrossRefPubMedPubMedCentralGoogle Scholar
  15. Danielyan L, Beer-Hammer S, Stolzing A, Schafer R, Siegel G, Fabian C, Kahle P, Biedermann T, Lourhmati A, Buadze M, Novakovic A, Proksch B, Gleiter CH, Frey WH, Schwab M (2014) 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 Transplant 23(Suppl 1):S123–S139CrossRefPubMedGoogle Scholar
  16. Desikan RS, Cabral HJ, Hess CP, Dillon WP, Glastonbury CM, Weiner MW, Schmansky NJ, Greve DN, Salat DH, Buckner RL, Fischl B (2009) Alzheimer’s Disease Neuroimaging Initiative. Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer’s disease. Brain 132:2048–2057CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ehrhart J, Darlington D, Kuzmin-Nichols N, Sanberg CD, Sawmiller DR, Sanberg PR, Tan J (2016) Biodistribution of infused human umbilical cord blood cells in Alzheimer’s disease-like murine model. Cell Transplant 25:195–199CrossRefPubMedGoogle Scholar
  18. Ende N, Chen R, Ende-Harris D (2001) Human umbilical cord blood cells ameliorate Alzheimer’s disease in transgenic mice. J Med 32:241–247PubMedGoogle Scholar
  19. Ennis WJ, Sui A, Bartholomew A (2013) Stem cells and healing: impact on inflammation. Adv Wound Care (New Rochelle) 2:369–378CrossRefGoogle Scholar
  20. Esmaeilzade B, Nobakht M, Joghataei MT, Rahbar Roshandel N, Rasouli H, Samadi Kuchaksaraei A, Hosseini SM, Najafzade N, Asalgoo S, Hejazian LB, Moghani GF (2012) Delivery of epidermal neural crest stem cells (EPI-NCSC) to hippocamp in Alzheimer’s disease rat model. Iran Biomed J 16:1–9PubMedPubMedCentralGoogle Scholar
  21. Garcia KO, Ornellas FL, Martin PK, Patti CL, Mello LE, Frussa-Filho R, Han SW, Longo BM (2014) 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 6:30CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S (2010) Cell-mediated neuroprotection in a mouse model of human tauopathy. J Neurosci 30:9973–9983CrossRefPubMedGoogle Scholar
  23. Han C, Sun X, Liu L, Jiang H, Shen Y, Xu X, Li J, Zhang G, Huang J, Lin Z, Xiong N, Wang T (2016) Exosomes and their therapeutic potentials of stem cells. Stem Cells Int 7653489Google Scholar
  24. Hebert LE, Weuve J, Scherr PA, Evans DA (2013) Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology 80:1778–1783CrossRefPubMedPubMedCentralGoogle Scholar
  25. Hickman SE, Allison EK, El Khoury J (2008) Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci 28:8354–8360CrossRefPubMedPubMedCentralGoogle Scholar
  26. Huang T, He D, Kleiner G, Kuluz J (2007) Neuron-like differentiation of adipose-derived stem cells from infant piglets in vitro. J Spinal Cord Med 30(Suppl 1):S35–S40CrossRefPubMedPubMedCentralGoogle Scholar
  27. Jeynes B, Provias J (2011) The case for blood-brain barrier dysfunction in the pathogenesis of Alzheimer’s disease. J Neurosci Res 89:22–28CrossRefPubMedGoogle Scholar
  28. Juan Yang, Song Li, Xi-Biao He, Cheng Cheng, Weidong Le (2016) Induced pluripotent stem cells in Alzheimer’s disease: applications for diseasemodeling and cell-replacement therapy. Mol Neurodegener. 2016; 11: 39. Published online May 17. doi:  https://doi.org/10.1186/s13024-016-0106-3
  29. Kamiya N, Ueda M, Igarashi H, Nishiyama Y, Suda S, Okubo S, Inaba T, Katayama Y (2013) In vivo monitoring of arterially transplanted bone marrow mononuclear cells in a rat transient focal brain ischemia model using magnetic resonance imaging. Neurol Res 35:573–579CrossRefPubMedGoogle Scholar
  30. Kim JS, Kim YH, Kim JH, Kang KW, Tae EL, Youn H, Kim D, Kim SK, Kwon JT, Cho MH, Lee YS, Jeong JM, Chung JK, Lee DS (2012) Development and in vivo imaging of a PET/MRI nanoprobe with enhanced NIR fluorescence by dye encapsulation. Nanomedicine (Lond) 7:219–229CrossRefGoogle Scholar
  31. Kim KS, Kim HS, Park JM, Kim HW, Park MK, Lee HS, Lim DS, Lee TH, Chopp M, Moon J (2013) Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer’s disease model. Neurobiol Aging 34:2408–2420CrossRefPubMedGoogle Scholar
  32. Kim JA, Ha S, Shin KY, Kim S, Lee KJ, Chong YH, Chang KA, Suh YH (2015a) Neural stem cell transplantation at critical period improves learning and memory through restoring synaptic impairment in Alzheimer’s disease mouse model. Cell Death Dis 6:e1789CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kim HJ, Seo SW, Chang JW, Lee JI, Kim CH, Chin J, Choi SJ, Kwon H, Yun HJ, Lee JM, Kim ST, Choe YS, Lee KH, Na DL (2015b) 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 (NY) 1:95–102Google Scholar
  34. Kimbrel EA, Lanza R (2015) Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat Rev Drug Discov 14:681–692CrossRefPubMedGoogle Scholar
  35. Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R (2016) The current landscape of the mesenchymal stromal cell secretome: a new paradigm for cell-free regeneration. Cytotherapy 18:13–24CrossRefPubMedGoogle Scholar
  36. Kondo T, Asai M, Tsukita K, KutokuY OY, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O, Hibino S, Choshi T, Nakahata T, Hioki H, Kaneko T, Naitoh M, Yoshikawa K, Yamawaki S, Suzuki S, Hata R, Ueno S, Seki T, Kobayashi K, Toda T, Murakami K, Irie K, Klein WL, Mori H, Asada T, Takahashi R, Iwata N, Yamanaka S, Inoue H (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12:487–496CrossRefPubMedGoogle Scholar
  37. Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S (2014) Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 6:552–570CrossRefPubMedPubMedCentralGoogle Scholar
  38. Lee ST, Chu K, Jung KH, Kim SJ, Kim DH, Kang KM, Hong NH, Kim JH, Ban JJ, Park HK, Kim SU, Park CG, Lee SK, Kim M, Roh JK (2008) Anti-inflammatory mechanism of intravascular neural stem cell transplantation in hemorrhagic stroke. Brain 131:616–629CrossRefPubMedGoogle Scholar
  39. Lee JK, Jin HK, Bae JS (2009) Bone marrow-derivedmesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neurosci Lett 450:136–141CrossRefPubMedGoogle Scholar
  40. Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, Bae JS (2010) 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 28:329–343PubMedGoogle Scholar
  41. Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, OhW YYS, Suh JG, Lee BH, Jin HK, Bae JS (2012) 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 33:588–602CrossRefPubMedGoogle Scholar
  42. Lehtivuori H, Bhattacharya S, Angenent-Mari NM, Satyshur KA, Forest KT (2015) Removal of chromophoreproximal polar atoms decreases water content and increases fluorescence in a near infrared phytofluor. Front Mol Biosci 2:65CrossRefPubMedPubMedCentralGoogle Scholar
  43. Li X, Liu X, Shi D, Wen X (2015) Particle systems for stem cell applications. J Biomed Nanotechnol 11:1107–1123CrossRefPubMedGoogle Scholar
  44. Liu F, Xuan A, Chen Y, Zhang J, Xu L, Yan Q, Long D (2014) Combined effect of nerve growth factor and brainderived brainderived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms. Mol Med Rep 10:1739–1745CrossRefPubMedPubMedCentralGoogle Scholar
  45. Mahmoudifar N, Doran PM (2015) Mesenchymal stem cells derived from human adipose tissue. Methods Mol Biol 1340:53–64.  https://doi.org/10.1007/978-1-4939-2938-2_4 CrossRefPubMedGoogle Scholar
  46. Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK (2003) Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest 111:71–79CrossRefPubMedPubMedCentralGoogle Scholar
  47. Marei HES, Althani A, Afifi N, Abd-Elmaksoud A, Bernardini CFM, Pescatori M, Maira G, Paldino E, Manni L, Casalbore P, Cenciarelli C (2013) Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation. PLoS One 8:e82206CrossRefPubMedPubMedCentralGoogle Scholar
  48. Menon S, Shailendra S, Renda A, Longaker M, Quarto N (2016) An overview of direct somatic reprogramming: the ins and outs of iPSCs. Int J Mol Sci 17. pii, E141Google Scholar
  49. Moghadam FH, Alaie H, Karbalaie K, Tanhaei S, Nasr Esfahani MH, Baharvand H (2009) Transplantation of primed or unprimed mouse embryonic stem cell-derived neural precursor cells improves cognitive function in Alzheimerian rats. Differentiation 78:59–68CrossRefPubMedGoogle Scholar
  50. Nagarajan S, Zhang Y (2011) Upconversion fluorescent nanoparticles as a potential tool for in-depth imaging. Nanotechnology 22:395101CrossRefPubMedGoogle Scholar
  51. Oh SH, Kim HN, Park HJ, Shin JY, Lee PH (2015) Mesenchymal stem cells increase hippocampal neurogenesis and neuronal differentiation by enhancing the Wnt signaling pathway in an Alzheimer’s disease model. Cell Transplant 24:1097–1109CrossRefPubMedGoogle Scholar
  52. Page MJ, AL L¸o, David T, LeBeau AM, Cattaruzza F, Castro HC, VanBrocklin HF, Coughlin SR, Craik CS (2015) Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography. Nat Commun 6:8448CrossRefPubMedPubMedCentralGoogle Scholar
  53. Paul G, Anisimov SV (2013) The secretome of mesenchymal stem cells: potential implications for neuroregeneration. Biochimie 95:2246–2256CrossRefPubMedGoogle Scholar
  54. Peng Y, Huang S, Cheng B, Nie X, Enhe J, Feng C, Fu X (2013) Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases. Ageing Res Rev 12:103–115CrossRefPubMedGoogle Scholar
  55. Poduslo JF, Ramakrishnan M, Holasek SS, Ramirez- Alvarado M, Kandimalla KK, Gilles EJ, Curran GL, Wengenack TM (2007) In vivo targeting of antibody fragments to the nervous system for Alzheimer’s disease immunotherapy and molecular imaging of amyloid plaques. J Neurochem 102:420–433CrossRefPubMedGoogle Scholar
  56. Poduslo JF, Hultman KL, Curran GL, Preboske GM, Chamberlain R, Marjanska M, Garwood M, Jack CR Jr, Wengenack TM (2011) Targeting vascular amyloid in arterioles of Alzheimer disease transgenic mice with amyloid β protein antibody-coated nanoparticles. J Neuropathol Exp Neurol 70, 653–661Google Scholar
  57. Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, Kim YJ, Jo JY, Yoon EJ, Choi HJ, Kwon E (2011) Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 20:1297–1308CrossRefPubMedGoogle Scholar
  58. Rafii MS, Baumann TL, Bakay RA, Ostrove JM, Siffert J, Fleisher AS, Herzog CD, Barba D, Pay M, Salmon DP, ChuY KJH, Bishop K, Keator D, Potkin S, Bartus RT (2014) A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer’s disease. Alzheimers Dement 10:571–581CrossRefPubMedGoogle Scholar
  59. Rohban R, RudolfPieber T (2017) Mesenchymal stem and progenitor cells in regeneration: tissue specificity and regenerative potential. Stem Cells Int 2017:1–16.  https://doi.org/10.1155/2017/5173732 CrossRefGoogle Scholar
  60. Romanov YA, Svintsitskaya VA, Smirnov VN (2003) Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 21:105–110CrossRefPubMedGoogle Scholar
  61. Rosemann A (2015) Stem cell treatments for neurodegenerative diseases: challenges from a science, business and healthcare perspective. Neurodegener Dis Manag 5:85–87CrossRefPubMedGoogle Scholar
  62. Rosenholm JM, Gulin-Sarfraz T, Mamaeva V, Niemi R, Ozliseli E, Desai D, Antfolk D, von Haartman E, Lindberg D, Prabhakar N, Nareoja T, Sahlgren C (2016) Prolonged dye release from mesoporous silica-based imaging probes facilitates long-term optical tracking of cell populations in vivo. Small 12:1578–1592CrossRefPubMedGoogle Scholar
  63. Ruiz de Almodovar C, Lambrechts D, Mazzone M, Carmeliet P (2009) Role and therapeutic potential of VEGF in the nervous system. Physiol Rev 89:607–648CrossRefPubMedGoogle Scholar
  64. Salem H, Pesso N, Colpo G, Teixeira AL (2016) Moving from the dish to the clinical practice: a decade of lessons and perspectives from the pre-clinical and clinical stem cell studies for Alzheimer’s disease. J Alzheimers Dis 53(3):1209–1230.  https://doi.org/10.3233/JAD-160250 CrossRefPubMedGoogle Scholar
  65. Shin JW, Lee JK, Lee JE, Min WK, Schuchman EH, Jin HK, Bae JS (2011) Combined effects of hematopoietic progenitor cell mobilization from bone marrow by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the brain using stromal cell-derived factor-1_ in an Alzheimer’s disease mouse model. Stem Cells 29:1075–1089CrossRefPubMedGoogle Scholar
  66. Smith DK, He M, Zhang CL, Zheng JC (2016) The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders. Prog Neurobiol 157:212–229.  https://doi.org/10.1016/j.pneurobio.2016.01.006 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefGoogle Scholar
  68. Toyoshima A, Yasuhara T, Kameda M, Morimoto J, Takeuchi H, Wang F, Sasaki T, Sasada S, Shinko A, Wakamori T, Okazaki M, Kondo A, Agari T, Borlongan CV, Date I (2015) Intra-arterial transplantation of allogeneic mesenchymal stem cells mounts neuroprotective effects in a transient ischemic stroke model in rats: analyses of therapeutic time window and its mechanisms. PLoS One 10:e0127302CrossRefPubMedPubMedCentralGoogle Scholar
  69. Vendrame M, Cassady J, Newcomb J, Butler T, Pennypacker KR, Zigova T, Sanberg CD, Sanberg PR, Willing AE (2004) Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 35:2390–2395CrossRefPubMedGoogle Scholar
  70. Villa C, Erratico S, Razini P, Farini A, Meregalli M, Belicchi M, Torrente Y (2011) In vivo tracking of stem cell by nanotechnologies: future prospects for mouse to human translation. Tissue Eng Part B Rev 17:1–11CrossRefPubMedGoogle Scholar
  71. Von der Haar K, Lavrentieva A, Stahl F, Scheper T, Blume C (2015) Lost signature: progress and failures in in vivo tracking of implanted stem cells. Appl Microbiol Biotechnol 99:9907–9922CrossRefPubMedGoogle Scholar
  72. Walker JR, Pacoma R, Watson J, Ou W, Alves J, Mason DE, Peters EC, Urbina HD, Welzel G, Althage A, Liu B, Tuntland T, Jacobson LH, Harris JL, Schumacher AM (2013) Enhanced proteolytic clearance of plasma A_ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice. J Neurosci 33:2457–2464CrossRefPubMedGoogle Scholar
  73. Wegner KD, Hildebrandt N (2015) Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors. Chem Soc Rev 44:4792–4834CrossRefPubMedGoogle Scholar
  74. Wenk GL (2003) Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry 64(Suppl 9):7–10PubMedGoogle Scholar
  75. Yang H, Yang H, Xie Z, Wei L, Bi J (2013) Systemic transplantation of human umbilical cord derived mesenchymal stem cells-educated T regulatory cells improved the impaired cognition in A_PPswe/PS1dE9 transgenic mice. PLoS One 8:e69129CrossRefPubMedPubMedCentralGoogle Scholar
  76. Yang B, Brahmbhatt A, Nieves Torres E, Thielen B, McCall DL, Engel S, Bansal A, Pandey MK, Dietz AB, Leof EB, DeGrado TR, Mukhopadhyay D, Misra S (2016) Tracking and therapeutic value of human adipose tissue derived mesenchymal stem cell transplantation in reducing venous neo-intimal hyperplasia associated with arterio-venous fistula. Radiology 279:513–522CrossRefPubMedGoogle Scholar
  77. Yun HM, Kim HS, Park KR, Shin JM, Kang AR, il Lee K, Song S, Kim YB, Han SB, Chung HM, Hong JT (2013) Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1-42-infused mouse model of Alzheimer’s disease. Cell Death Dis 4:e958CrossRefPubMedPubMedCentralGoogle Scholar
  78. Zhang R, Liu Y, Yan K, Chen L, Chen XR, Li P, Chen FF, Jiang XD (2013) Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J Neuroinflammation 10:106PubMedPubMedCentralGoogle Scholar
  79. Zhang W, Gu GJ, Shen X, Zhang Q, Wang GM, Wang PJ (2015) Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer’s disease-like pathology. Neurobiol Aging 36:1282–1292CrossRefPubMedGoogle Scholar
  80. Zhang Q, Wu HH, Wang Y, Gu GJ, Zhang W, Xia R (2016) Neural stem cell transplantation decreases neuroinflammation in a transgenic mouse model of Alzheimer’s disease. J Neurochem 136:815–825CrossRefPubMedGoogle Scholar
  81. Zhao JY, Chen G, Gu YP, Cui R, Zhang ZL, Yu ZL, Tang B, Zhao YF, Pang DW (2016) Ultrasmall magnetically engineered Ag2Se quantum dots for instant efficient labeling and whole-body high-resolution multimodal real-time tracking of cell-derived microvesicles. J Am Chem Soc 138:1893–1903CrossRefPubMedGoogle Scholar
  82. Zipser BD, Johanson CE, Gonzalez L, Berzin TM, Tavares R, Hulette CM, Vitek MP, Hovanesian V, Stopa EG (2007) Microvascular injury and blood-brain barrier leakage in Alzheimer’s disease. Neurobiol Aging 28:977–986CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Haitham Salem
    • 1
  • Gabriela D. Colpo
    • 1
  • Antonio L. Teixeira
    • 1
  1. 1.Neuropsychiatry Program, Department of Psychiatry and Behavioral SciencesUniversity of Texas Health Science Center at HoustonHoustonUSA

Personalised recommendations