Cellular and Molecular Neurobiology

, Volume 39, Issue 2, pp 181–209 | Cite as

Recent Expansions on Cellular Models to Uncover the Scientific Barriers Towards Drug Development for Alzheimer’s Disease

  • Sunil Kumar DubeyEmail author
  • Munnangi Siva Ram
  • Kowthavarapu Venkata Krishna
  • Ranendra Narayan Saha
  • Gautam Singhvi
  • Mukta Agrawal
  • Ajazuddin
  • Swarnlata Saraf
  • Shailendra Saraf
  • Amit AlexanderEmail author
Review Paper


Globally, the central nervous system (CNS) disorders appear as the most critical pathological threat with no proper cure. Alzheimer’s disease (AD) is one such condition frequently observed with the aged population and sometimes in youth too. Most of the research utilizes different animal models for in vivo study of AD pathophysiology and to investigate the potency of the newly developed therapy. These in vivo models undoubtably provide a powerful investigation tool to study human brain. Although, it sometime fails to mimic the exact environment and responses as the human brain owing to the distinctive genetic and anatomical features of human and rodent brain. In such condition, the in vitro cell model derived from patient specific cell or human cell lines can recapitulate the human brain environment. In addition, the frequent use of animals in research increases the cost of study and creates various ethical issues. Instead, the use of in vitro cellular models along with animal models can enhance the translational values of in vivo models and represent a better and effective mean to investigate the potency of therapeutics. This strategy also limits the excessive use of laboratory animal during the drug development process. Generally, the in vitro cell lines are cultured from AD rat brain endothelial cells, the rodent models, human astrocytes, human brain capillary endothelial cells, patient derived iPSCs (induced pluripotent stem cells) and also from the non-neuronal cells. During the literature review process, we observed that there are very few reviews available which describe the significance and characteristics of in vitro cell lines, for AD investigation. Thus, in the present review article, we have compiled the various in vitro cell lines used in AD investigation including HBMEC, BCECs, SHSY-5Y, hCMEC/D3, PC-2 cell line, bEND3 cells, HEK293, hNPCs, RBE4 cells, SK-N-MC, BMVECs, CALU-3, 7W CHO, iPSCs and cerebral organoids cell lines and different types of culture media such as SCM, EMEM, DMEM/F12, RPMI, EBM and 3D-cell culture.

Graphical Abstract


Alzheimer’s disease In vitro cell line BCECs HBMEC SK-N-MC 



The author wants to acknowledge Rungta College of Pharmaceutical Sciences and Research, Kohka, Kurud Road, Bhilai, Chhattisgarh, India for providing necessary facilities for the compilation of this work.

Author Contributions

Sunil Kumar Dubey and Amit Alexander drafted the structure of manuscript, drawn all the figures and prepared the tables. Munnangi Siva Ram and Kowthavarapu Venkata Krishna initially wrote the paper. Ranendra Narayan Saha and Gautam Singhvi corrected the first draft and made primary corrections. Ajazuddin, Swarnlata Saraf and Shailendra Saraf reviewed the manuscript and made some comments. Finally, Amit Alexander and Mukta Agrawal corrected the manuscript, revised the figures, handled the language and approved the manuscript for submission.

Compliance with Ethical Standards

Ethical Approval

No ethical issues involved.

Conflict of interest

We declare we have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyBirla Institute of Technology and Science, Pilani (BITS-PILANI)RajasthanIndia
  2. 2.Department of BiotechnologyBirla Institute of Technology and Science, Pilani (BITS-PILANI)DubaiUnited Arab Emirates
  3. 3.Department of PharmaceuticsRungta College of Pharmaceutical Sciences and ResearchBhilaiIndia
  4. 4.University Institute of Pharmacy, Pt. Ravishankar Shukla UniversityRaipurIndia
  5. 5.Hemchand Yadav UniversityDurgIndia

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