Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells

Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by... Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer’s disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25–35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25–35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25–35. ucMSCs-CM also promoted the phagocytosis of Aβ25–35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25–35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25–35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Neuroscience Springer Journals

Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells

Download PDF
12 pages

Loading next page...
 
/lp/springer_journal/umbilical-cord-mesenchymal-stem-cells-conditioned-medium-promotes-a-25-3qHVoHD2Y7
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Biomedicine; Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology
ISSN
0895-8696
eISSN
1559-1166
DOI
10.1007/s12031-018-1075-5
pmid
29845511
Publisher site
See Article on Publisher Site

Abstract

Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer’s disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25–35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25–35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25–35. ucMSCs-CM also promoted the phagocytosis of Aβ25–35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25–35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25–35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.

Journal

Journal of Molecular Neuroscience – Springer Journals

Published: May 29, 2018

References

  • World Alzheimer Report
  • Microglia contributes to plaque growth by cell death due to uptake of amyloid beta in the brain of Alzheimer's disease mouse model
    Baik, SH; Kang, S; Son, SM; Mook-Jung, I
  • Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease
    Boland, B; Kumar, A; Lee, S; Platt, FM; Wegiel, J; Yu, WH; Nixon, RA
  • Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation
    Cantinieaux, D; Quertainmont, R; Blacher, S; Rossi, L; Wanet, T; Noel, A; Brook, G; Schoenen, J; Franzen, R
  • Autophagy in microglia degrades extracellular beta-amyloid fibrils and regulates the NLRP3 inflammasome
    Cho, MH; Cho, K; Kang, HJ; Jeon, EY; Kim, HS; Kwon, HJ; Kim, HM; Kim, DH; Yoon, SY
  • Extracellular vesicles in brain tumors and neurodegenerative diseases
    Ciregia, F; Urbani, A; Palmisano, G
  • Dysfunction of autophagy and endosomal–lysosomal pathways: roles in pathogenesis of down syndrome and Alzheimer's disease
    Colacurcio, DJ; Pensalfini, A; Jiang, Y; Nixon, RA
  • Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis
    Cui, Y; Ma, S; Zhang, C; Cao, W; Liu, M; Li, D; Lv, P; Xing, Q; Qu, R; Yao, N; Yang, B; Guan, F
  • Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice
    Dagher, NN; Najafi, AR; Kayala, KMN; Elmore, MRP; White, TE; Medeiros, R; West, BL; Green, KN
  • The cellular phase of Alzheimer's disease
    Strooper, B; Karran, E
  • Conditioned media from cell lines: a complementary model to clinical specimens for the discovery of disease-specific biomarkers
    Dowling, P; Clynes, M
  • Biodistribution of infused human umbilical cord blood cells in Alzheimer's disease-like murine model
    Ehrhart, J; Darlington, D; Kuzmin-Nichols, N; Sanberg, CD; Sawmiller, DR; Sanberg, PR; Tan, J
  • An early and late peak in microglial activation in Alzheimer's disease trajectory
    Fan, Z; Brooks, DJ; Okello, A; Edison, P
  • Scara1 deficiency impairs clearance of soluble amyloid-beta by mononuclear phagocytes and accelerates Alzheimer's-like disease progression
    Frenkel, D; Wilkinson, K; Zhao, L; Hickman, SE; Means, TK; Puckett, L; Farfara, D; Kingery, ND; Weiner, HL; Khoury, J
  • Alzheimer's disease: from firing instability to homeostasis network collapse
    Frere, S; Slutsky, I
  • Characterization of ameboid microglia isolated from developing mammalian brain
    Giulian, D; Baker, TJ
  • Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-beta oligomers
    Godoy, MA; Saraiva, LM; Carvalho, LRP; Vasconcelos-Dos-Santos, A; Beiral, HJV; Ramos, AB; Silva, LRP; Leal, RB; Monteiro, VHS; Braga, CV; Araujo-Silva, CA; Sinis, LC; Santos, VB; Brunswick, THK; Alcantara, CL; Lima, A; Cunha, ESNLD; Galina, A; Vieyra, A; Felice, FG; Mendez-Otero, R; Ferreira, ST
  • Aβ1–42 monomers or oligomers have different effects on autophagy and apoptosis
    Guglielmotto, M; Monteleone, D; Piras, A; Valsecchi, V; Tropiano, M; Ariano, S; Fornaro, M; Vercelli, A; Puyal, J; Arancio, O; Tabaton, M; Tamagno, E
  • Mesenchymal stem cells can prevent alterations in behavior and neurogenesis induced by Ass25-35 administration
    Hamisha, KN; Tfilin, M; Yanai, J; Turgeman, G
  • Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer’s disease mice
    Hickman, SE; Allison, EK; Khoury, JE
  • Cysteine-rich domain of scavenger receptor AI modulates the efficacy of surface targeting and mediates oligomeric Aβ internalization
    Huang, F-L; Shiao, Y-J; Hou, S-J; Yang, C-N; Chen, Y-J; Lin, C-H; Shie, F-S; Tsay, H-J
  • Alzheimer mechanisms and therapeutic strategies
    Huang, Y; Mucke, L
  • Accelerating stem cell trials for Alzheimer's disease
    Hunsberger, JG; Rao, M; Kurtzberg, J; Bulte, JWM; Atala, A; LaFerla, FM; Greely, HT; Sawa, A; Gandy, S; Schneider, LS; Doraiswamy, PM
  • An Aβ42 uptake and degradation via Rg3 requires an activation of caveolin, clathrin and Aβ-degrading enzymes in microglia
    Jang, SK; Yu, JM; Kim, ST; Kim, GH; Park, DW; Lee, DI; Joo, SS
  • Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease
    Janssen, L; Dubbelaar, ML; Holtman, IR; Boer-Bergsma, J; Eggen, BJ; Boddeke, HW; Deyn, PP; Dam, D
  • Impact of insulin degrading enzyme and neprilysin in Alzheimer's disease biology: characterization of putative cognates for therapeutic applications
    Jha, NK; Jha, SK; Kumar, D; Kejriwal, N; Sharma, R; Ambasta, RK; Kumar, P
  • LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells
    Jiang, P; Mizushima, N
  • Differential clearance of rat and human bone marrow-derived mesenchymal stem cells from the brain after intra-arterial infusion in rats
    Khabbal, J; Kerkela, E; Mitkari, B; Raki, M; Nystedt, J; Mikkonen, V; Bergstrom, K; Laitinen, S; Korhonen, M; Jolkkonen, J
  • 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
    Kim, DH; Lee, D; Chang, EH; Kim, JH; Hwang, JW; Kim, JY; Kyung, JW; Kim, SH; Oh, JS; Shim, SM; Na, DL; Oh, W; Chang, JW
  • Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-beta plaques
    Kim, JY; Kim, DH; Kim, JH; Lee, D; Jeon, HB; Kwon, SJ; Kim, SM; Yoo, YJ; Lee, EH; Choi, SJ; Seo, SW; Lee, JI; Na, DL; Yang, YS; Oh, W; Chang, JW
  • Recent advances in the neurobiology and neuropharmacology of Alzheimer's disease
    Kumar, K; Kumar, A; Keegan, RM; Deshmukh, R
  • Alzheimer's disease
    Lane, CA; Hardy, J; Schott, JM
  • A reporter cell system to monitor autophagy based on p62/SQSTM1
    Larsen, KB; Lamark, T; Overvatn, A; Harneshaug, I; Johansen, T; Bjorkoy, G
  • The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease
    Lee, HJ; Lee, JK; Lee, H; Shin, JW; Carter, JE; Sakamoto, T; Jin, HK; Bae, JS
  • Stem cell therapy: a prospective treatment for Alzheimer's disease
    Lee, JH; Oh, I-H; Lim, HK
  • Autophagy and Alzheimer's disease
    Li, Q; Liu, Y; Sun, M
  • Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy
    Li, T; Xia, M; Gao, Y; Chen, Y; Xu, Y
  • Decreased clearance of CNS beta-amyloid in Alzheimer's disease
    Mawuenyega, KG; Sigurdson, W; Ovod, V; Munsell, L; Kasten, T; Morris, JC; Yarasheski, KE; Bateman, RJ
  • Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities
    Menzies, FM; Fleming, A; Caricasole, A; Bento, CF; Andrews, SP; Ashkenazi, A; Fullgrabe, J; Jackson, A; Jimenez Sanchez, M; Karabiyik, C; Licitra, F; Lopez Ramirez, A; Pavel, M; Puri, C; Renna, M; Ricketts, T; Schlotawa, L; Vicinanza, M; Won, H; Zhu, Y; Skidmore, J; Rubinsztein, DC
  • Abeta-degrading enzymes: potential for treatment of Alzheimer disease
    Miners, JS; Barua, N; Kehoe, PG; Gill, S; Love, S
  • Methods in mammalian autophagy research
    Mizushima, N; Yoshimori, T; Levine, B
  • Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study
    Nixon, RA; Wegiel, J; Kumar, A; Yu, WH; Peterhoff, C; Cataldo, A; Cuervo, AM
  • Assays to monitor autophagy progression in cell cultures
    Orhon, I; Reggiori, F
  • The role of extracellular vesicles in neurodegenerative diseases
    Quek, C; Hill, AF
  • Mesenchymal stem cells avoid allogeneic rejection
    Ryan, JM; Barry, FP; Murphy, JM; Mahon, BP
  • Mesenchymal stem cells enhance autophagy and increase beta-amyloid clearance in Alzheimer disease models
    Shin, JY; Park, HJ; Kim, HN; Oh, SH; Bae, JS; Ha, HJ; Lee, PH
  • The endocytic pathway in microglia during health, aging and Alzheimer's disease
    Sole-Domenech, S; Cruz, DL; Capetillo-Zarate, E; Maxfield, FR
  • Inflammation in Alzheimer's disease: lessons learned from microglia-depletion models
    Spangenberg, EE; Green, KN
  • Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-beta pathology
    Spangenberg, EE; Lee, RJ; Najafi, AR; Rice, RA; Elmore, MR; Blurton-Jones, M; West, BL; Green, KN
  • Comparison of different fetal bovine serums in cultivation of human umbilical cord stroma-derived mesenchymal stem cells
    Sun, W; Xu, Z; Liu, R; Yuan, Z; Feng, H
  • Microglia in Alzheimer's disease: the good, the bad and the ugly
    Tejera, D; Heneka, MT
  • Homeostasis of microglia in the adult brain: review of novel microglia depletion systems
    Waisman, A; Ginhoux, F; Greter, M; Bruttger, J
  • Mesenchymal stem cell-derived extracellular vesicles suppresses iNOS expression and ameliorates neural impairment in Alzheimer's disease mice
    Wang, SS; Jia, J; Wang, Z
  • Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer's disease
    Wang, X; Ma, S; Yang, B; Huang, T; Meng, N; Xu, L; Xing, Q; Zhang, Y; Zhang, K; Li, Q; Zhang, T; Wu, J; Yang, GL; Guan, F; Wang, J
  • Targeting microglia for the treatment of Alzheimer's disease
    Wes, PD; Sayed, FA; Bard, F; Gan, L
  • Endo-lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?
    Whyte, LS; Lau, AA; Hemsley, KM; Hopwood, JJ; Sargeant, TJ
  • Alzheimer disease: soluble TREM2 in CSF sheds light on microglial activation in AD
    Wood, H
  • Stem cell therapy for Alzheimer's disease: hope or hype?
    Wray, S; Fox, NC
  • Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits
    Yang, DS; Stavrides, P; Mohan, PS; Kaushik, S; Kumar, A; Ohno, M; Schmidt, SD; Wesson, D; Bandyopadhyay, U; Jiang, Y; Pawlik, M; Peterhoff, CM; Yang, AJ; Wilson, DA; St George-Hyslop, P; Westaway, D; Mathews, PM; Levy, E; Cuervo, AM; Nixon, RA
  • Monitoring and measuring autophagy
    Yoshii, SR; Mizushima, N
  • Microglial Abeta receptors in Alzheimer's disease
    Yu, Y; Ye, RD
  • Clearance of cerebral Abeta in Alzheimer's disease: reassessing the role of microglia and monocytes
    Zuroff, L; Daley, D; Black, KL; Koronyo-Hamaoui, M