Alzheimer's in 3D Culture: Challenges and Perspectives

Overview

Journal Bioessays

Publisher Wiley

Specialties Biology
Cell Biology
Molecular Biology

Date 2015 Aug 8

PMID 26252541

Citations 49

Authors

Carla DAvanzo

Jenna Aronson

Young Hye Kim

Se Hoon Choi

Rudolph E Tanzi

Doo Yeon Kim

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The "β-amyloid cascade hypothesis" of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery.

Citing Articles

Cell culture research in aging and Alzheimer's disease: The strategic use/reuse of untreated controls and savings people's tax dollars.

Kshirsagar S, Islam M, Reddy A, Reddy P J Alzheimers Dis Rep. 2025; 9:25424823241310716.

PMID: 40034533 PMC: 11864248. DOI: 10.1177/25424823241310716.

Integrative pathway analysis across humans and 3D cellular models identifies the p38 MAPK-MK2 axis as a therapeutic target for Alzheimer's disease.

Yeganeh P, Kwak S, Jorfi M, Koler K, Kalatturu T, von Maydell D Neuron. 2024; 113(2):205-224.e8.

PMID: 39610246 PMC: 11757051. DOI: 10.1016/j.neuron.2024.10.029.

Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice.

Kubota Y, Shigetomi E, Saito K, Shinozaki Y, Kobayashi K, Tanaka M Int J Mol Sci. 2024; 25(22).

PMID: 39596168 PMC: 11595037. DOI: 10.3390/ijms252212100.

Stem cell-based approaches for developmental neurotoxicity testing.

Ku J, Asuri P Front Toxicol. 2024; 6:1402630.

PMID: 39238878 PMC: 11374538. DOI: 10.3389/ftox.2024.1402630.

Generation of Alzheimer's Disease Model Derived from Induced Pluripotent Stem Cells with Gene Mutation.

Kim Y, Yun B, Ye B, Kim B Biomedicines. 2024; 12(6).

PMID: 38927400 PMC: 11201172. DOI: 10.3390/biomedicines12061193.

References

Mohamet L, Miazga N, Ward C . Familial Alzheimer's disease modelling using induced pluripotent stem cell technology. World J Stem Cells. 2014; 6(2):239-47. PMC: 3999781. DOI: 10.4252/wjsc.v6.i2.239. View

Cohen R, Rezai-Zadeh K, Weitz T, Rentsendorj A, Gate D, Spivak I . A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aβ, and frank neuronal loss. J Neurosci. 2013; 33(15):6245-56. PMC: 3720142. DOI: 10.1523/JNEUROSCI.3672-12.2013. View

Selkoe D . Alzheimer's disease is a synaptic failure. Science. 2002; 298(5594):789-91. DOI: 10.1126/science.1074069. View

Liedmann A, Frech S, Morgan P, Rolfs A, Frech M . Differentiation of human neural progenitor cells in functionalized hydrogel matrices. Biores Open Access. 2013; 1(1):16-24. PMC: 3560381. DOI: 10.1089/biores.2012.0209. View

Hardy J, Selkoe D . The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297(5580):353-6. DOI: 10.1126/science.1072994. View

Holcomb L, Gordon M, McGowan E, Yu X, Benkovic S, Jantzen P . Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med. 1998; 4(1):97-100. DOI: 10.1038/nm0198-097. View

Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T . Modeling familial Alzheimer's disease with induced pluripotent stem cells. Hum Mol Genet. 2011; 20(23):4530-9. DOI: 10.1093/hmg/ddr394. View

Li H, Wijekoon A, Leipzig N . 3D differentiation of neural stem cells in macroporous photopolymerizable hydrogel scaffolds. PLoS One. 2012; 7(11):e48824. PMC: 3492243. DOI: 10.1371/journal.pone.0048824. View

Shi Y, Kirwan P, Smith J, MacLean G, Orkin S, Livesey F . A human stem cell model of early Alzheimer's disease pathology in Down syndrome. Sci Transl Med. 2012; 4(124):124ra29. PMC: 4129935. DOI: 10.1126/scitranslmed.3003771. View

10.

Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira A, Herland A . A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials. 2013; 35(5):1420-8. DOI: 10.1016/j.biomaterials.2013.11.028. View

11.

Ortinau S, Schmich J, Block S, Liedmann A, Jonas L, Weiss D . Effect of 3D-scaffold formation on differentiation and survival in human neural progenitor cells. Biomed Eng Online. 2010; 9:70. PMC: 2996398. DOI: 10.1186/1475-925X-9-70. View

12.

Glenner G . The pathobiology of Alzheimer's disease. Annu Rev Med. 1989; 40:45-51. DOI: 10.1146/annurev.me.40.020189.000401. View

13.

Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M . beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc Natl Acad Sci U S A. 2001; 98(21):12245-50. PMC: 59799. DOI: 10.1073/pnas.211412398. View

14.

Haycock J . 3D cell culture: a review of current approaches and techniques. Methods Mol Biol. 2010; 695:1-15. DOI: 10.1007/978-1-60761-984-0_1. View

15.

Mucke L, Masliah E, Yu G, Mallory M, Rockenstein E, Tatsuno G . High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000; 20(11):4050-8. PMC: 6772621. View

16.

Henley D, Sundell K, Sethuraman G, Dowsett S, May P . Safety profile of semagacestat, a gamma-secretase inhibitor: IDENTITY trial findings. Curr Med Res Opin. 2014; 30(10):2021-32. DOI: 10.1185/03007995.2014.939167. View

17.

Muratore C, Rice H, Srikanth P, Callahan D, Shin T, Benjamin L . The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum Mol Genet. 2014; 23(13):3523-36. PMC: 4049307. DOI: 10.1093/hmg/ddu064. View

18.

Park J, Lee B, Jeong G, Hyun J, Lee C, Lee S . Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease. Lab Chip. 2014; 15(1):141-50. DOI: 10.1039/c4lc00962b. View

19.

Hughes C, Postovit L, Lajoie G . Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics. 2010; 10(9):1886-90. DOI: 10.1002/pmic.200900758. View

20.

Baker B, Chen C . Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J Cell Sci. 2012; 125(Pt 13):3015-24. PMC: 3434846. DOI: 10.1242/jcs.079509. View