Skip to main content

Advertisement

SpringerLink
Log in

Modeling of Alzheimer’s Disease to Study the Efficacy of Cell Therapy (Review)

  • CELL TECHNOLOGIES IN BIOLOGY AND MEDICINE
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We analyzed the main approaches to the modeling of Alzheimer’s disease for studying the effectiveness of cell therapy. Recent advances in regenerative medicine in the field of neuroscience create prospects for the use of various cell preparations for the treatment of Alzheimer’s disease. Experimental data on the use of neural stem/progenitor cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells in various models of Alzheimer’s disease are presented. Of particular importance is the standardization of protocols. The use of a standardized protocol in modeling of Alzheimer’s disease will allow a comparative analysis of the effectiveness and safety of treatment to identify the optimal cell preparation. The data obtained on experimental animals can form the basis for further preclinical and clinical studies of cell therapy for Alzheimer’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Liu XY, Yang LP, Zhao L. Stem cell therapy for Alzheimer’s disease. World J. Stem Cells. 2020;12(8):787-802. doi: https://doi.org/10.4252/wjsc.v12.i8.787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur. J. Neurol. 2018;25(1):59-70. doi: https://doi.org/10.1111/ene.13439

    Article  CAS  PubMed  Google Scholar 

  3. Si Z, Wang X. Stem cell therapies in Alzheimer’s disease: applications for disease modeling. J. Pharmacol. Exp. Ther. 2021;377(2):207-217. doi: https://doi.org/10.1124/jpet.120.000324

    Article  CAS  PubMed  Google Scholar 

  4. Appleby BS, Cummings JL. Discovering new treatments for Alzheimer’s disease by repurposing approved medications. Curr. Top. Med. Chem. 2013;13(18):2306-2327. doi: https://doi.org/10.2174/15680266113136660162

    Article  CAS  PubMed  Google Scholar 

  5. Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin. Interv. Aging. 2008;3(2):211-225.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Qin C, Wang K, Zhang L, Bai L. Stem cell therapy for Alzheimer’s disease: An overview of experimental models and reality. Animal Model Exp. Med. 2022;5(1):15-26. doi: https://doi.org/10.1002/ame2.12207

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bryan KJ, Lee HG, Perry G, Smith MA, Casadesus G. Transgenic mouse models of Alzheimer’s disease: behavioral testing and considerations. Methods of Behavior Analysis in Neuroscience. Buccafusco JJ, ed. Boca Raton, 2009. P. 2-14.

  8. Pentkowski NS, Rogge-Obando KK, Donaldson TN, Bouquin SJ, Clark BJ. Anxiety and Alzheimer’s disease: behavioral analysis and neural basis in rodent models of Alzheimer’s-related neuropathology. Neurosci. Biobehav. Rev. 2021;127:647-658. doi: https://doi.org/10.1016/j.neubiorev.2021.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Puzzo D, Lee L, Palmeri A, Calabrese G, Arancio O. Behavioral assays with mouse models of Alzheimer’s disease: practical considerations and guidelines. Biochem. Pharmacol. 2014;88(4):450-467. doi: https://doi.org/10.1016/j.bcp.2014.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tian H, Ding N, Guo M, Wang S, Wang Z, Liu H, Yang J, Li Y, Ren J, Jiang J, Li Z. Analysis of learning and memory ability in an Alzheimer’s disease mouse model using the Morris water maze. J. Vis. Exp. 2019;(152). doi: https://doi.org/10.3791/60055

  11. Sacrey LA, Alaverdashvili M, Whishaw IQ. Similar hand shaping in reaching-for-food (skilled reaching) in rats and humans provides evidence of homology in release, collection, and manipulation movements. Behav. Brain Res. 2009;204(1):153-161. doi: https://doi.org/10.1016/j.bbr.2009.05.035

    Article  PubMed  Google Scholar 

  12. Lawlor PA, Bland RJ, Das P, Price RW, Holloway V, Smithson L, Dicker BL, During MJ, Young D, Golde TE. Novel rat Alzheimer’s disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels. Mol. Neurodegener. 2007;2:11. doi: https://doi.org/10.1186/1750-1326-2-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Song Z, Zheng M, Ding J, Xu Y, Ji MJ, Liu C. Detecting amyloid-β accumulation via immunofluorescent staining in a mouse model of Alzheimer’s disease. J. Vis. Exp. 2021. N 170. doi: https://doi.org/10.3791/62254

  14. Galeano P, Martino Adami PV, Do Carmo S, Blanco E, Rotondaro C, Capani F, Castaño EM, Cuello AC, Morelli L. Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease. Front. Behav. Neurosci. 2014;8:321. doi: https://doi.org/10.3389/fnbeh.2014.00321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Serneels L, T’Syen D, Perez-Benito L, Theys T, Holt MG, De Strooper B. Modeling the β-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer’s disease. Mol. Neurodegener. 2020;15(1):60. doi: https://doi.org/10.1186/s13024-020-00399-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Filip T, Mairinger S, Neddens J, Sauberer M, Flunkert S, Stanek J, Wanek T, Okamura N, Langer O, Hutter-Paier B, Kuntner C. Characterization of an APP/tau rat model of Alzheimer’s disease by positron emission tomography and immunofluorescent labeling. Alzheimers Res. Ther. 2021;13(1):175. doi: https://doi.org/10.1186/s13195-021-00916-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Baerends E, Soud K, Folke J, Pedersen AK, Henmar S, Konrad L, Lycas MD, Mori Y, Pakkenberg B, Woldbye DPD, Dmytriyeva O, Pankratova S. Modeling the early stages of Alzheimer’s disease by administering intracerebroventricular injections of human native Aβ oligomers to rats. Acta Neuropathol. Commun. 2022;10(1):113. doi: https://doi.org/10.1186/s40478-022-01417-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dmytriyeva O, Belmeguenai A, Bezin L, Soud K, Drucker Woldbye DP, Gøtzsche CR, Pankratova S. Short erythropoietin-derived peptide enhances memory, improves long-term potentiation, and counteracts amyloid beta-induced pathology. Neurobiol. Aging. 2019;81:88-101. doi: https://doi.org/10.1016/j.neurobiolaging.2019.05.003

    Article  CAS  PubMed  Google Scholar 

  19. Singh A, Kumar A. Comparative analysis of intrahippocampal amyloid beta (1-42) and it is intracerebroventricular streptozotocin models of Alzheimer’s disease: possible behavioral, biochemical, mitochondrial, cellular and histopathological evidences. J. Alzheimers Dis. Parkinsonism. 2016;6(1). doi: https://doi.org/10.4172/2161-0460.1000208

  20. O’Hare E, Scopes DI, Treherne JM, Monaghan J, Palmer PM, Amijee H, Kim EM. Novel anti-inflammatory compound SEN1176 alleviates behavioral deficits induced following bilateral intrahippocampal injection of aggregated amyloid-β1-42. J. Alzheimers Dis. 2011;25(2):219-229. doi: https://doi.org/10.3233/JAD-2011-100044

    Article  CAS  PubMed  Google Scholar 

  21. Zhu D, Yang N, Liu YY, Zheng J, Ji C, Zuo PP. M2 macrophage transplantation ameliorates cognitive dysfunction in amyloid-β-treated rats through regulation of microglial polarization. J. Alzheimers Dis. 2016;52(2):483-495. doi: https://doi.org/10.3233/JAD-151090

  22. Takeda S, Sato N, Niisato K, Takeuchi D, Kurinami H, Shinohara M, Rakugi H, Kano M, Morishita R. Validation of Abeta1-40 administration into mouse cerebroventricles as an animal model for Alzheimer disease. Brain Res. 2009;1280:137-147. doi: https://doi.org/10.1016/j.brainres.2009.05.035

    Article  CAS  PubMed  Google Scholar 

  23. Paulo SL, Rodrigues RS, Shvachiy L, Ribeiro FF, Solá S, Sebastião AM, Xapelli S. Neurogenesis in a rat model of sporadic Alzheimer’s disease: PS227. Porto Biomed. J. 2017;2(5):205. doi: https://doi.org/10.1016/j.pbj.2017.07.072

    Article  PubMed  PubMed Central  Google Scholar 

  24. Facchinetti R, Bronzuoli MR, Scuderi C. An animal model of Alzheimer disease based on the intrahippocampal injection of amyloid β-peptide (1-42). Methods Mol. Biol. 2018;1727:343-352. doi: https://doi.org/10.1007/978-1-4939-7571-6_25

    Article  CAS  PubMed  Google Scholar 

  25. Ravelli KG, Rosário BD, Camarini R, Hernandes MS, Britto LR. Intracerebroventricular streptozotocin as a model of Alzheimer’s disease: neurochemical and behavioral characterization in mice. Neurotox. Res. 2017;31(3):327-333. doi: https://doi.org/10.1007/s12640-016-9684-7

    Article  CAS  PubMed  Google Scholar 

  26. Gáspár A, Hutka B, Ernyey AJ, Tajti BT, Varga BT, Zádori ZS, Gyertyán I. Performance of the intracerebroventricularly injected streptozotocin Alzheimer’s disease model in a translationally relevant, aged and experienced rat population. Sci. Rep. 2022;12(1):20247. doi: https://doi.org/10.1038/s41598-022-24292-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Petrasek T, Skurlova M, Maleninska K, Vojtechova I, Kristofikova Z, Matuskova H, Sirova J, Vales K, Ripova D, Stuchlik A. A rat model of Alzheimer’s disease based on Abeta42 and pro-oxidative substances exhibits cognitive deficit and alterations in glutamatergic and cholinergic neurotransmitter systems. Front. Aging Neurosci. 2016;8:83. doi: https://doi.org/10.3389/fnagi.2016.00083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Andrew MK, Tierney MC. The puzzle of sex, gender and Alzheimer’s disease: Why are women more often affected than men? Women’s Health (Lond). 2018;14(2):1745506518817995. doi: https://doi.org/10.1177/1745506518817995

    Article  CAS  PubMed Central  Google Scholar 

  29. Campos HC, Ribeiro DE, Hashiguchi D, Hukuda DY, Gimenes C, Romariz SAA, Ye Q, Tang Y, Ulrich H, Longo BM. Distinct effects of the hippocampal transplantation of neural and mesenchymal stem cells in a transgenic model of Alzheimer’s disease. Stem Cell Rev. Rep. 2022;18(2):781-791. doi: https://doi.org/10.1007/s12015-021-10321-9

    Article  CAS  PubMed  Google Scholar 

  30. McGinley LM, Kashlan ON, Bruno ES, Chen KS, Hayes JM, Kashlan SR, Raykin J, Johe K, Murphy GG, Feldman EL. Human neural stem cell transplantation improves cognition in a murine model of Alzheimer’s disease. Sci. Rep. 2018;8(1):14776. doi: https://doi.org/10.1038/s41598-018-33017-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Petrasek T, Vojtechova I, Lobellova V, Popelikova A, Janikova M, Brozka H, Houdek P, Sladek M, Sumova A, Kristofikova Z, Vales K, Stuchlík A. The McGill transgenic rat model of Alzheimer’s disease displays cognitive and motor impairments, changes in anxiety and social behavior, and altered circadian activity. Front. Aging Neurosci. 2018;10:250. doi: https://doi.org/10.3389/fnagi.2018.00250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhu Q, Zhang N, Hu N, Jiang R, Lu H, Xuan A, Long D, Chen Y. Neural stem cell transplantation improves learning and memory by protecting cholinergic neurons and restoring synaptic impairment in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer’s disease. Mol. Med. Rep. 2020;21(3):41172-1180. doi: https://doi.org/10.3892/mmr.2020.10918

    Article  CAS  Google Scholar 

  33. Zhang HA, Yuan CX, Liu KF, Yang QF, Zhao J, Li H, Yang QH, Song D, Quan ZZ, Qing H. Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy. Neural Regen. Res. 2022;17(1):152-162. doi: https://doi.org/10.4103/1673-5374.314324

    Article  CAS  PubMed  Google Scholar 

  34. Kloskowska E, Pham TM, Nilsson T, Zhu S, Oberg J, Codita A, Pedersen LA, Pedersen JT, Malkiewicz K, Winblad B, Folkesson R, Benedikz E. Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer’s disease. J. Cell. Mol. Med. 2010;14(6B):1816-1823. doi: https://doi.org/10.1111/j.1582-4934.2009.00809.x

    Article  CAS  PubMed  Google Scholar 

  35. Doshmanziari M, Shirian S, Kouchakian MR, Moniri SF, Jangnoo S, Mohammadi N, Zafari F. Mesenchymal stem cells act as stimulators of neurogenesis and synaptic function in a rat model of Alzheimer’s disease. Heliyon. 2021;7(9):e07996. doi: https://doi.org/10.1016/j.heliyon.2021.e07996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kazemiha M, Sarveazad A, Moradi F, Ramezanpour F, Vosoogh M, Doshmanziari M, Shariatpanahi M, Eftekharzadeh M. Histological and behavioral alterations following hADSCs intravenous administration in Alzheimer’s rat model. Thrita 2019;8(1):e99975. doi: https://doi.org/10.5812/thrita.99975

    Article  Google Scholar 

  37. Finder VH. Alzheimer’s disease: a general introduction and pathomechanism. J. Alzheimers Dis. 2010;22(Suppl. 3):5-19. doi: https://doi.org/10.3233/JAD-2010-100975

    Article  CAS  PubMed  Google Scholar 

  38. Fujiwara N, Shimizu J, Takai K, Arimitsu N, Saito A, Kono T, Umehara T, Ueda Y, Wakisaka S, Suzuki T, Suzuki N. Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells. Neurosci. Lett. 2013;557(Pt B):129-134.

    Article  CAS  PubMed  Google Scholar 

  39. Delarue Q, Guerout N. Transplantation of olfactory ensheathing cells: properties and therapeutic effects after transplantation into the lesioned nervous system. Neuroglia. 2022;3(2):1-22. doi: https://doi.org/10.3390/neuroglia3010001

    Article  Google Scholar 

  40. Stepanova OV, Voronova AD, Chadin AV, Valikhov MP, Semkina AS, Karsuntseva EK, Chekhonin IV, Shishkina VS, Reshetov IV, Chekhonin VP. Efficiency of human olfactory ensheathing cell transplantation into spinal cysts to improve mobility of the hind limbs. Stem Cells Dev. 2019;28(18):1253-1263. doi: https://doi.org/10.1089/scd.2019.0092

    Article  PubMed  Google Scholar 

  41. Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, Huber J, Szarek D, Okurowski S, Szewczyk P, Gorski A, Raisman G. Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant. 2013;22(9):1591-1612. doi: https://doi.org/10.3727/096368912X663532

    Article  PubMed  Google Scholar 

  42. Voronova AD, Stepanova OV, Valikhov MP, Chadin AV, Dvornikov AS, Reshetov IV, Chekhonin VP. Preparation of human olfactory ensheathing cells for the therapy of spinal cord injuries. Bull. Exp. Biol. Med. 2018;164(4):523-527. doi: https://doi.org/10.1007/s10517-018-4025-x

    Article  CAS  PubMed  Google Scholar 

  43. Yao R, Murtaza M, Velasquez JT, Todorovic M, Rayfield A, Ekberg J, Barton M, St John J. Olfactory ensheathing cells for spinal cord injury: sniffing out the issues. Cell Transplant. 2018;27(6):879-889. doi: https://doi.org/10.1177/0963689718779353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mackay-Sim A, Féron F, Cochrane J, Bassingthwaighte L, Bayliss C, Davies W, Fronek P, Gray C, Kerr G, Licina P, Nowitzke A, Perry C, Silburn PA, Urquhart S, Geraghty T. Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain. 2008;131(Pt 9):2376-2386. doi: https://doi.org/10.1093/brain/awn173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stepanova OV, Voronova AD, Sosnovtseva AO, Stepanenko AA, Chadin AV, Karsuntseva EK, Fursa GA, Valikhov MP, Semkina AS, Vorobyev PO, Reshetov IV, Chekhonin VP. Study of the therapeutic efficiency of transduced olfactory ensheathing cells in spinal cord cysts. Stem Cells Dev. 2022;31(1-2):9-17. doi: https://doi.org/10.1089/scd.2021.0265

    Article  CAS  PubMed  Google Scholar 

  46. Stepanova OV, Voronova AD, Chadin AV, Valikhov MP, Abakumov MA, Reshetov IV, Chekhonin VP. Isolation of rat olfactory ensheathing cells and their use in the therapy of posttraumatic cysts of the spinal cord. Bull. Exp. Biol. Med. 2018;165(1):132-135. doi: https://doi.org/10.1007/s10517-018-4114-x

    Article  CAS  PubMed  Google Scholar 

  47. Stepanova OV, Voronova AD, Fursa GA, Karsuntseva EK, Valikhov MP, Chadin AV, Vishnevskii DA, Reshetov IV, Chekhonin VP. Preparation of adhesion culture of neural stem/progenitor cells of the olfactory mucosa for the treatment of spinal cord injuries. Bull. Exp. Biol. Med. 2020;170(1):3158-163. doi: https://doi.org/10.1007/s10517-020-05023-0

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. V. P. Serbsky National Medical Research Centre of Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia

    A. D. Voronova, E. K. Karsuntseva, O. V. Stepanova, A. V. Chadin, V. V. Shishkina, S. S. Andretsova, G. A. Fursa, S. V. Shport & V. P. Chekhonin

  2. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia

    G. A. Fursa & V. P. Chekhonin

  3. University Clinical Hospital, I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia

    I. V. Reshetov

  4. M. V. Lomonosov Moscow State University, Moscow, Russia

    S. S. Andretsova

  5. E. I. Chazov National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia

    O. V. Stepanova

Authors
  1. A. D. Voronova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. K. Karsuntseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. V. Stepanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. V. Chadin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. V. Shishkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. S. Andretsova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. A. Fursa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. V. Shport
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. I. V. Reshetov
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. V. P. Chekhonin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. D. Voronova.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 71-76, June, 2023

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Voronova, A.D., Karsuntseva, E.K., Stepanova, O.V. et al. Modeling of Alzheimer’s Disease to Study the Efficacy of Cell Therapy (Review). Bull Exp Biol Med 175, 524–529 (2023). https://doi.org/10.1007/s10517-023-05899-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-023-05899-8

Keywords

Search

Navigation