Volume 1 , Issue 1 , PP: 17-34, 2024 | Cite this article as | XML | Html | PDF | Full Length Article
Nima Khodadadi 1 * , Benyamin Abdollahzadeh 2
Doi: https://doi.org/10.54216/MOR.010102
Following this background, this review discusses the advanced technologies such as AI, micro-fluids, and automated platforms that this differentiation protocol could help achieve in regenerative medicine. Stem cell research, essential in tissue engineering, disease modeling, and drug development, is challenging through heterogeneity, scalability, and reproducibility, as observed in differentiation procedures. Machine learning and deep learning patterns have become more effective in predicting cellular behavior, tracking cellular stations, and optimizing differentiation methods for current stem cell technology. These methods also reduce observer bias, increase the throughput of high-throughput screening, and advance modeling to precise therapeutic applications. At the same time, microfluidic and automated systems provide nearly perfect control over differentiation stimuli, recreating the in vivo conditions with the ability to control spatial and temporal gradients. This integration between AI and microengineering has promoted 3D culture systems, lab-on-a-chip technologies, and biosensors, enabling reproducible and efficient differentiation results. There is still much to accomplish, such as the problem of obtaining uniform stem cell populations or decoding the tissue context. This field incorporates several interdisciplinary advancements such as stimuli-responsive systems and computational modeling; it envisages new horizons in regenerative medicine, transforming stem cell-based therapeutic technologies to their optimum level for personalized medicine and other advanced tissue engineering applications.
The areas of Expertise include Stem Cell Differentiation , Artificial Intelligence , Regenerative Medicine , Microfluidics , Machine Learning , Tissue Engineering
[1] “(PDF) A Review of Dental Pulp Stem Cells in Permanent Teeth.” Accessed: Dec. 02, 2024. [Online]. Available: https://www.researchgate.net/publication/386223450_A_Review_of_Dental_Pulp_Stem_Cells_in_Permanent_Teeth
[2] J. M. Tainio, S. Vanhatupa, S. Miettinen, and J. Massera, “Borosilicate bioactive glasses with added Mg/Sr enhances human adipose-derived stem cells osteogenic commitment and angiogenic properties,” Journal of Materials Science: Materials in Medicine 2024 35:1, vol. 35, no. 1, pp. 1–12, Nov. 2024, doi: 10.1007/S10856-024-06830-X.
[3] A. Algarín, D. Martín, P. Daza, G. Huertas, and A. Yúfera, “Integrated Sensors for Electric Stimulation of Stem Cells: A Review on MicroElectrode Arrays (MEAs) Based Systems,” Sensors and Actuators Reports, p. 100264, Nov. 2024, doi: 10.1016/J.SNR.2024.100264.
[4] M. Srinivasan, S. R. Thangaraj, K. Ramasubramanian, P. P. Thangaraj, and K. V. Ramasubramanian, “Exploring the Current Trends of Artificial Intelligence in Stem Cell Therapy: A Systematic Review,” Cureus, vol. 13, no. 12, p. e20083, Dec. 2021, doi: 10.7759/CUREUS.20083.
[5] H. Nosrati and M. Nosrati, “Artificial Intelligence in Regenerative Medicine: Applications and Implications,” Biomimetics, vol. 8, no. 5, p. 442, Sep. 2023, doi: 10.3390/BIOMIMETICS8050442.
[6] M. Mai et al., “Morphology-based deep learning approach for predicting adipogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs),” Front Cell Dev Biol, vol. 11, p. 1329840, Nov. 2023, doi: 10.3389/FCELL.2023.1329840/BIBTEX.
[7] P. Ertl, D. Sticker, V. Charwat, C. Kasper, and G. Lepperdinger, “Lab-on-a-chip technologies for stem cell analysis,” Trends Biotechnol, vol. 32, no. 5, pp. 245–253, May 2014, doi: 10.1016/J.TIBTECH.2014.03.004.
[8] J. Zhang, X. Wei, R. Zeng, F. Xu, and X. J. Li, “Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip,” Future Sci OA, vol. 3, no. 2, p. FSO187, May 2017, doi: 10.4155/FSOA-2016-0091.
[9] S. Yazdian Kashani et al., “An integrated microfluidic device for stem cell differentiation based on cell-imprinted substrate designed for cartilage regeneration in a rabbit model,” Materials Science and Engineering: C, vol. 121, p. 111794, Feb. 2021, doi: 10.1016/J.MSEC.2020.111794.
[10] F. Zhou et al., “Subcellular RNA distribution and its change during human embryonic stem cell differentiation,” Stem Cell Reports, vol. 19, no. 1, pp. 126–140, Jan. 2024, doi: 10.1016/j.stemcr.2023.11.007.
[11] W. Jin et al., “Comprehensive review on single-cell RNA sequencing: A new frontier in Alzheimer’s disease research,” Ageing Res Rev, vol. 100, p. 102454, Sep. 2024, doi: 10.1016/J.ARR.2024.102454.
[12] E. Lee, H. K. Choi, Y. Kwon, and K. B. Lee, “Real-Time, Non-Invasive Monitoring of Neuronal Differentiation Using Intein-Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell-Based Biosensors,” Adv Funct Mater, vol. 34, no. 29, p. 2400394, Jul. 2024, doi: 10.1002/ADFM.202400394.
[13] R. G. L. da Silva, “The advancement of artificial intelligence in biomedical research and health innovation: challenges and opportunities in emerging economies,” Globalization and Health 2024 20:1, vol. 20, no. 1, pp. 1–19, May 2024, doi: 10.1186/S12992-024-01049-5.
[14] Y. S. Eom, J. H. Park, and T. H. Kim, “Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials,” J Funct Biomater, vol. 14, no. 9, p. 483, Sep. 2023, doi: 10.3390/JFB14090483.
[15] F. Li, Y. Ye, X. Lei, and W. Zhang, “Effects of Microgravity on Early Embryonic Development and Embryonic Stem Cell Differentiation: Phenotypic Characterization and Potential Mechanisms,” Front Cell Dev Biol, vol. 9, p. 797167, Dec. 2021, doi: 10.3389/FCELL.2021.797167/BIBTEX.
[16] J. Issa et al., “Artificial-Intelligence-Based Imaging Analysis of Stem Cells: A Systematic Scoping Review,” Biology (Basel), vol. 11, no. 10, Oct. 2022, doi: 10.3390/BIOLOGY11101412.
[17] Y. Zhu, R. Huang, Z. Wu, S. Song, L. Cheng, and R. Zhu, “Deep learning-based predictive identification of neural stem cell differentiation,” Nat Commun, vol. 12, no. 1, Dec. 2021, doi: 10.1038/S41467-021-22758-0.
[18] K. Marzec-Schmidt, N. Ghosheh, S. R. Stahlschmidt, B. Küppers-Munther, J. Synnergren, and B. Ulfenborg, “Artificial Intelligence Supports Automated Characterization of Differentiated Human Pluripotent Stem Cells,” Stem Cells, vol. 41, no. 9, pp. 850–861, Sep. 2023, doi: 10.1093/STMCLS/SXAD049.
[19] D. Toparlak et al., “Artificial cells drive neural differentiation,” Sci Adv, vol. 6, no. 38, Sep. 2020, doi: 10.1126/SCIADV.ABB4920.
[20] K. W. Cui, L. Engel, C. E. Dundes, T. C. Nguyen, K. M. Loh, and A. R. Dunn, “Spatially controlled stem cell differentiation via morphogen gradients: A comparison of static and dynamic microfluidic platforms.,” J Vac Sci Technol A, vol. 38 3, no. 3, May 2020, doi: 10.1116/1.5142012.
[21] P. Sokolowska, K. Zukowski, I. Lasocka, L. Szulc-Dabrowska, and E. Jastrzebska, “Human mesenchymal stem cell (hMSC) differentiation towards cardiac cells using a new microbioanalytical method,” Analyst, vol. 145, no. 8, pp. 3017–3028, Apr. 2020, doi: 10.1039/C9AN02366F.
[22] L. Oss-Ronen, R. A. Redden, and P. I. Lelkes, “Enhanced Induction of Definitive Endoderm Differentiation of Mouse Embryonic Stem Cells in Simulated Microgravity.,” Stem Cells Dev, vol. 29, no. 19, pp. 1275–1284, Oct. 2020, doi: 10.1089/SCD.2020.0097.
[23] J. C. Ardila Riveros et al., “Automated optimization of endoderm differentiation on chip,” Lab Chip, vol. 21, no. 23, pp. 4685–4695, Dec. 2021, doi: 10.1039/D1LC00565K.
[24] L. Li et al., “Optimization of Factor Combinations for Stem Cell Differentiations on a Design-of-Experiment Microfluidic Chip.,” Anal Chem, vol. 92, no. 20, pp. 14228–14235, Oct. 2020, doi: 10.1021/ACS.ANALCHEM.0C03488.
[25] W.-L. Yang, Z. Huo, S. Chen, D. Zhu, T.-J. Liu, and D.-F. Lee, “Abstract 185: Monitoring of stem cell differentiation to mature hepatocytes with a machine learning-based AI model,” Bioinformatics and Systems Biology, vol. 81, no. 13_Supplement, pp. 185–185, Jul. 2021, doi: 10.1158/1538-7445.AM2021-185.
[26] B. J. O’Grady and E. S. Lippmann, “Recent Advancements in Engineering Strategies for Manipulating Neural Stem Cell Behavior,” Curr Tissue Microenviron Rep, vol. 1, no. 2, pp. 41–47, Jun. 2020, doi: 10.1007/S43152-020-00003-Y.
[27] N. Konstantinides and C. Desplan, “Neuronal differentiation strategies: insights from single-cell sequencing and machine learning,” Development, vol. 147, no. 23, Dec. 2020, doi: 10.1242/DEV.193631.
[28] D. Urrutia-Cabrera et al., “Combinatorial Approach of Binary Colloidal Crystals and CRISPR Activation to Improve Induced Pluripotent Stem Cell Differentiation into Neurons.,” ACS Appl Mater Interfaces, vol. 14, no. 7, pp. 8669–8679, Feb. 2022, doi: 10.1021/ACSAMI.1C17975.
[29] F. Ravera, E. Efeoglu, and H. J. Byrne, “Vibrational Spectroscopy for In Vitro Monitoring Stem Cell Differentiation,” Molecules, vol. 25, no. 23, Dec. 2020, doi: 10.3390/MOLECULES25235554.
[30] M. J. Kang, Y. W. Cho, and T. H. Kim, “Progress in Nano-Biosensors for Non-Invasive Monitoring of Stem Cell Differentiation,” Biosensors (Basel), vol. 13, no. 5, May 2023, doi: 10.3390/BIOS13050501.
[31] S. W. Tang, W. Y. Tong, S. W. Pang, N. H. Voelcker, and Y. W. Lam, “Deconstructing, replicating, and engineering tissue microenvironment for stem cell differentiation.,” Tissue Eng Part B Rev, vol. 26, no. 6, pp. 540–554, Dec. 2020, doi: 10.1089/TEN.TEB.2020.0044.
[32] K. Marzec-Schmidt, N. Ghosheh, S. R. Stahlschmidt, B. Küppers-Munther, J. Synnergren, and B. Ulfenborg, “Artificial Intelligence Supports Automated Characterization of Differentiated Human Pluripotent Stem Cells,” Stem Cells, vol. 41, no. 9, pp. 850–861, Sep. 2023, doi: 10.1093/STMCLS/SXAD049.
[33] M. A. Skylar-Scott et al., “An orthogonal differentiation platform for genomically programming stem cells, organoids, and bioprinted tissues,” bioRxiv, Jul. 2020, doi: 10.1101/2020.07.11.198671.
[34] E. Kegeles, T. Perepelkina, and P. Baranov, “Semi-Automated Approach for Retinal Tissue Differentiation,” Transl Vis Sci Technol, vol. 9, no. 10, pp. 1–15, Sep. 2020, doi: 10.1167/TVST.9.10.24.
[35] Z. Li, A. Napolitano, M. Fedele, X. Gao, and F. Napolitano, “AI identifies potent inducers of breast cancer stem cell differentiation based on adversarial learning from gene expression data,” bioRxiv, Aug. 2023, doi: 10.1101/2023.08.21.554075.
[36] P. K. Dabla, D. Gruson, B. Gouget, S. Bernardini, and E. Homsak, “Lessons Learned from the COVID-19 Pandemic: Emphasizing the Emerging Role and Perspectives from Artificial Intelligence, Mobile Health, and Digital Laboratory Medicine,” EJIFCC, vol. 32, no. 2, p. 224, 2021, Accessed: Dec. 02, 2024. [Online]. Available: https://pmc.ncbi.nlm.nih.gov/articles/PMC8343043/
[37] Y. B. Pawar and A. R. Thool, “Navigating the Genetic Landscape: A Comprehensive Review of Novel Therapeutic Strategies for Retinitis Pigmentosa Management,” Cureus, vol. 16, no. 8, p. e67046, Aug. 2024, doi: 10.7759/CUREUS.67046.
[38] G. Tao, S. Yang, J. Xu, L. Wang, and B. Yang, “Global research trends and hotspots of artificial intelligence research in spinal cord neural injury and restoration—a bibliometrics and visualization
analysis,” Frontiers in Neurology , vol. 15, p. 1361235, Apr. 2024, doi: 10.3389/FNEUR.2024.1361235/BIBTEX.
[39] P. K. Dabla, D. Gruson, B. Gouget, S. Bernardini, and E. Homsak, “Lessons Learned from the COVID-19 Pandemic: Emphasizing the Emerging Role and Perspectives from Artificial Intelligence, Mobile Health, and Digital Laboratory Medicine,” EJIFCC, vol. 32, no. 2, p. 224, 2021, Accessed: Dec. 02, 2024. [Online]. Available: https://pmc.ncbi.nlm.nih.gov/articles/PMC8343043/
[40] G. Minnick, “Advancements in Microscale Tensile Testing: A Novel Device for the High Throughput Analysis of Two-photon Polymerized Microfibers in Liquid,” Dissertations and Doctoral Documents from University of Nebraska-Lincoln, 2023–, Jul. 2024, Accessed: Dec. 02, 2024. [Online]. Available: https://digitalcommons.unl.edu/dissunl/190
[41] Z. Wang, A. Hulikova, and P. Swietach, “Innovating cancer drug discovery with refined phenotypic screens,” Trends Pharmacol Sci, vol. 45, no. 8, pp. 723–738, Aug. 2024, doi: 10.1016/J.TIPS.2024.06.001/ASSET/DB65CB5C-7468-4B68-9C8C-F4D6E8FCD5B9/MAIN.ASSETS/GR3.JPG.
[42] H. G. Leufkens et al., “Four scenarios for the future of medicines and social policy in 2030,” Drug Discov Today, vol. 27, no. 8, pp. 2252–2260, Aug. 2022, doi: 10.1016/J.DRUDIS.2022.03.018.
[43] U. Demirkilic and B. Tosun, “The rise of artificial intelligence in vascular surgery: A bibliometric analysis (2020-2024),” Turkish Journal of Vascular Surgery, vol. 33, no. 2, pp. 103–103, Jul. 2024, Accessed: Dec. 02, 2024. [Online]. Available: https://turkishjournalofvascularsurgery.org/?mno=209813