Monitorización en tiempo real de células madre de alto potencial como elemento biológico innovador en biosensores
DOI:
https://doi.org/10.61164/hx215f69Palabras clave:
Biossensores; Células-tronco embrionárias; Biossensores de células; Monitoramento.Resumen
La convergencia entre la biotecnología de células madre y la tecnología de biosensores representa un avance significativo para la selección de fármacos y la medicina regenerativa. Las células madre embrionarias (CME), caracterizadas por su pluripotencia y capacidad de autorrenovación, ofrecen una fuente celular renovable y fisiológicamente relevante para la construcción de biosensores basados en células (BBC). A pesar de los retos técnicos relacionados con el mantenimiento de la viabilidad celular y la estandarización, el campo avanza hacia sistemas integrados de laboratorio en chip y biosensores de célula única, lo que promete revolucionar la farmacología de alto rendimiento y la medicina personalizada. En este artículo discutimos las plataformas de transducción compatibles, como las matrices de microelectrodos (MEA) y los sensores potenciométricos direccionables por luz (LAPS), y el papel de la nanoingeniería de superficies para optimizar la interfaz célula-transductor. Las principales aplicaciones incluyen la detección de cardiotoxicidad y neurotoxicidad de nuevos fármacos, la monitorización en tiempo real de la diferenciación celular y la detección de toxicidad ambiental. Este artículo explora los fundamentos de esta integración, destacando las CME (o sus derivados diferenciados) como elementos de reconocimiento biológico que convierten las respuestas celulares a estímulos externos en señales medibles.
Descargas
Referencias
AI, Z.; NIU. B.; YIN, Y.; XIANG, L.; SHI, G.; DUAN, K.; WANG, S.; HU, Y.; ZHANG, C.; ZHANG, C.; RONG, L.; KONG, R.; CHEN, T.; GUO, Y.; LIU, W.; LI, N.; ZHAO, S.; ZHU, X.; MAI, X.; LI, Y.; WU, Z.; ZHENG, Y.; FU, J.; JI, W.; LI, T. Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids. Cell Research, v. 33, n.9, p. 661-678, 2023. doi: 10.1038/s41422-023-00846-8. DOI: https://doi.org/10.1038/s41422-023-00846-8
AYDIN, T.; GURCAN, C.; TAHERI, H.; YILMAZER, A. Graphene Based Materials in Neural Tissue Regeneration. Adv Exp Med Biology, v.1107, p.129-142, 2018. doi: 10.1007/5584_2018_221. DOI: https://doi.org/10.1007/5584_2018_221
CHALKLEN, T.; JING, Q.; KAR-NARAYAN, S. Biosensors Based on Mechanical and Electrical Detection Techniques. Sensors (Basel), v.20, n.19, p.5605, 2020. doi: 10.3390/s20195605. DOI: https://doi.org/10.3390/s20195605
CHITHRANI, D. B. Optimization of Bio-Nano Interface Using Gold Nanostructures as a Model Nanoparticle System. Insciences Journal, v.1, n.3, 115-135, 2011. doi:10.5640/insc.0103115 DOI: https://doi.org/10.5640/insc.0103115
DIENEMANN, S.; WOHLENBERG, O. J.; GERSTENBERGER, J.G.; LAVRENTIEVA, A.; PEPELANOVA, I. 3D culture of neural progenitor cells in gelatin norbornene (GelNB) hydrogels: mechanical tuning and hypoxia characterization. Front Bioeng Biotechnology, v.13, p.1579580, 2025. doi: 10.3389/fbioe.2025.1579580. DOI: https://doi.org/10.3389/fbioe.2025.1579580
DORMEYER, W.; VAN, HOOF D.; BRAAM, S.R.; HECK, A.J.; MUMMERY, C.L.; KRIJGSVELD, J. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells. J Proteome Research, v.7, n.7, p.2936-51, 2008. doi: 10.1021/pr800056j. DOI: https://doi.org/10.1021/pr800056j
FAROUK, M.; EL-HAMEED, A.S.A.; ELDAMAK, A.R.; ELSHEAKH, D.N. Noninvasive blood glucose monitoring using a dual band microwave sensor with machine learning. Scientific Reports, v.15, n.1, p.16271, 2025. doi: 10.1038/s41598-025-94367-6. DOI: https://doi.org/10.1038/s41598-025-94367-6
FATHI, F.; RAHBARGHAZI, R.; RASHIDI, M.R. Label-free biosensors in the field of stem cell biology. Biosens Bioelectron. 2018 Mar 15;101:188-198. doi: 10.1016/j.bios.2017.10.028. DOI: https://doi.org/10.1016/j.bios.2017.10.028
GARCIA-JUNIOR, M.A.; ANDRADE, B.S.; LIMA, A.P.; SOARES, I.P.; NOTÁRIO, A.F.O.; BERNARDINO, S.S.; GUEVARA-VEJA, M.F.; HONÓRIO-SILVA, G.; MUNOZ, R.A.A.; JARDIM, A.C.G.; MARTINS, M.M.; GOULART, L.R.; CUNHA, T.M.; CARNEIRO, M.G.; SABINO-SILVA, R. Artificial-Intelligence Bio-Inspired Peptide for Salivary Detection of SARS-CoV-2 in Electrochemical Biosensor Integrated with Machine Learning Algorithms. Biosensors (Basel), v.15, n.2, p.75, 2025. doi: 10.3390/bios15020075. DOI: https://doi.org/10.3390/bios15020075
GILL, B.J.; GIBBONS, D.L.; ROUDSARI, L.C.; SAIK, J.E.; RIZVI, Z.H.; ROYBAL, J.D.; KURIE, J.M.; WEST, J.L. A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model. Cancer Research, v.72, n.22, p.6013-23, 2012. doi: 10.1158/0008-5472.CAN-12-0895. DOI: https://doi.org/10.1158/0008-5472.CAN-12-0895
HO, H.Y.; LI, M. Potential application of embryonic stem cells in Parkinson's disease: drug screening and cell therapy. Regenerative Medicine, v.1, n.2, p.175-82, 2006. doi: 10.2217/17460751.1.2.175. DOI: https://doi.org/10.2217/17460751.1.2.175
KIM, D.; KIM, S.B.; RYU, J.L.; HONG, H.; CHANG, J.H.; YOO, T.J.; JIN, X.; PARK, H.J.; HAN, C.; LEE, B.H.; CHOI, J.H.; YOO, H.W.; KIM, J.H.; WOO, D.H. Human Embryonic Stem Cell-Derived Wilson's Disease Model for Screening Drug Efficacy. Cells, v.9, n.4, p.872, 2020. doi: 10.3390/cells9040872. DOI: https://doi.org/10.3390/cells9040872
KANG, M.J.; CHO, Y.W.; KIM, T.H. Progress in Nano-Biosensors for Non-Invasive Monitoring of Stem Cell Differentiation. Biosensors (Basel), v.13, n.5, p.501, 2023. doi: 10.3390/bios13050501. DOI: https://doi.org/10.3390/bios13050501
KEUSGEN, M. Biosensors: new approaches in drug discovery. Naturwissenschaften, v.89, n.10, p.433-44, 2002. doi: 10.1007/s00114-002-0358-3. DOI: https://doi.org/10.1007/s00114-002-0358-3
LEE, E.; CHOI, H.K.; KWON, Y.; LEE, K.B. Real-Time, Non-Invasive Monitoring of Neuronal Differentiation Using Intein-Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell-Based Biosensors. Advanced Functional Materials, v.34, n.29, p.2400394, 2024. doi: 10.1002/adfm.202400394. DOI: https://doi.org/10.1002/adfm.202400394
LI. K.; HUNTWORK, R.H.C.; HORN, G.Q.; ALAM, S.M.; TOMARAS, G.D.; DENNISON, S.M. TitrationAnalysis: a tool for high throughput binding kinetics data analysis for multiple label-free platforms. Gates Open Research, v.7, p.107, 2024. doi: 10.12688/gatesopenres.14743.2. DOI: https://doi.org/10.12688/gatesopenres.14743.2
LIU, Q.; CA, H.; XIAO, L.; LI, R.; YANG, M.; WANG, P. Embryonic Stem Cells Biosensor and Its Application in Drug Analysis and Toxin Detection. in IEEE Sensors Journal, vol. 7, no. 12, pp. 1625-1631, 2007a. doi: 10.1109/JSEN.2007.908439. DOI: https://doi.org/10.1109/JSEN.2007.908439
LIU, Q.; HUANG, H.; CAI, H.; XU, Y.; LI, Y.; LI, R.; WANG, P. Embryonic stem cells as a novel cell source of cell-based biosensors. Biosens Bioelectron, v.22, n.6, p.810-5, 2007b. doi: 10.1016/j.bios.2006.03.006. DOI: https://doi.org/10.1016/j.bios.2006.03.006
MOLÈ, M.A.; COORENS, T.H.H.; SHAHBAZI, M.N.; WEBERLING, A.; WEATHERBEE, B.A.T.; GANTNER, C.W.; SANCHO-SERRA, C.; RICHARDSON, L.; DRINKWATER, A.; SYED, N.; ENGLEY, S.; SNELL, P.; CHRISTIE, L.; ELDER, K.; CAMPBELL, A.; FISHEL, S.; BEHJATI, S.; VENTO-TORMO, R.; ZERNICKA-GOETZ, M. A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre. Nat Communications, v.12, n.1, p.3679, 2021. doi: 10.1038/s41467-021-23758-w. DOI: https://doi.org/10.1038/s41467-021-23758-w
NOSRATI, H.; NOSRATI, M. Artificial Intelligence in Regenerative Medicine: Applications and Implications. Biomimetics (Basel), v.8, n.5, p.442, 2023. doi: 10.3390/biomimetics8050442. DOI: https://doi.org/10.3390/biomimetics8050442
ONO, T.; OKUDA, S.; USHIBA, S.; KANAI, Y.; MATSUMOTO, K. Challenges for Field-Effect-Transistor-Based Graphene Biosensors. Materials (Basel), v.17, n.2, p.333, 2024. doi: 10.3390/ma17020333. DOI: https://doi.org/10.3390/ma17020333
PENG, Y.; XIE, M.; DUAN, X.; HU, L.; YU, J.; ZENG, S.; WANG, Y.; OUYANG, Q.; LU, G.; LIN, G.; SUN, Y. Generation of a luciferase-expressing human embryonic stem cell line: NERCe002-A-2. Stem Cell Research, v.28, p.172-176, 2018. doi: 10.1016/j.scr.2018.02.010. DOI: https://doi.org/10.1016/j.scr.2018.02.010
PEREIRA, A. S.; SHITSUKA, D. M.; PEREIRA, F. J.; SHITSUKA, R. Metodologia da pesquisa científica. Santa Maria: 1⸰ed. UFSM. 2018, 119p. Disponível em:< https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf> Acesso em: 21 de novembro de 2025
SABRIN, S.; KARMOKAR, D.K.; KARMAKAR, N.C.; HONG, S.H.; HABIBULLAH, H.; SZILI, E.J. Opportunities of Electronic and Optical Sensors in Autonomous Medical Plasma Technologies. ACS Sensors, v.8, n.3, p.974-993, 2023. doi: 10.1021/acssensors.2c02579. DOI: https://doi.org/10.1021/acssensors.2c02579
SANO, T.; ZHANG, H.; LOSAKUL, R.; SCHMIDT, H. All-in-One Optofluidic Chip for Molecular Biosensing Assays. Biosensors (Basel), v.12, n.7, p.501, 2022. doi: 10.3390/bios12070501. DOI: https://doi.org/10.3390/bios12070501
SHAHBAZI, M.N.; WANG, T.; TAO, X; WEATHERBEE, B.A.T.; SUN, L.; ZHAN, Y.; KELLER, L.; SMITH, G.D.; PELLICER, A.; SCOTT, R.T. JR.; SELI, E.; ZERNICKA-GOETZ. M. Developmental potential of aneuploid human embryos cultured beyond implantation. Nat Communications, v.11, n.1, p.3987, 2020. doi: 10.1038/s41467-020-17764-7. DOI: https://doi.org/10.1038/s41467-020-17764-7
SHI, Y.; KOPPARAPU, N.; OHLER, L.; DICKINSON, D.J. Efficient and rapid fluorescent protein knock-in with universal donors in mouse embryonic stem cells. Development, v.150, p.10, dev201367, 2023. doi: 10.1242/dev.201367. DOI: https://doi.org/10.1242/dev.201367
Singh, S.; Podder, P.S.; Russo, M.; Henry, C.; Cinti, S. Tailored point-of-care biosensors for liquid biopsy in the field of oncology. Lab Chip, v.23, n.1, p.44-61, 2022. doi: 10.1039/d2lc00666a. DOI: https://doi.org/10.1039/D2LC00666A
STANLEY, S.A.; GAGNER, J.E.; DAMANPOUR, S.; YOSHIDA, M.; DORDICK, J.S.; FRIEDMAN, J.M. Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice. Science. 2012 May 4;336(6081):604-8. doi: 10.1126/science.1216753. DOI: https://doi.org/10.1126/science.1216753
TIAN, Z.; YU, T.; LIU, J.; WANG, T.; HIGUCHI, A. Introduction to stem cells. Progress in Molecular Biology and Translational Science, v.199, p.3-32, 2023. doi: 10.1016/bs.pmbts.2023.02.012. DOI: https://doi.org/10.1016/bs.pmbts.2023.02.012
VARVAŘOVSKÁ, L.; KUDRNA, P.; SOPKO, B.; JAROŠÍKOVÁ, T. The Development of a Specific Nanofiber Bioreceptor for Detection of Escherichia coli and Staphylococcus aureus from Air. Biosensors (Basel), v.14, n.5, p.234, 2024. doi: 10.3390/bios14050234. DOI: https://doi.org/10.3390/bios14050234
WANG, S.; RIAHI, R.; LI, N.; ZHANG, D.D.; WONG, P.K. Single cell nanobiosensors for dynamic gene expression profiling in native tissue microenvironments. Advanced Functional Materials, v.27, n.39, p.6034-8, 2015. doi: 10.1002/adma.201502814. DOI: https://doi.org/10.1002/adma.201502814
WNOROWSKI, A.; YANG, H.; WU, J.C. Progress, obstacles, and limitations in the use of stem cells in organ-on-a-chip models. Advanced Drug Delivery Reviews, v.140, p.3-11, 2019. doi: 10.1016/j.addr.2018.06.001. DOI: https://doi.org/10.1016/j.addr.2018.06.001
ZHANG, W.; ZHAO, Y.; YANG, Z.; YAN, J.; WANG, H.; NIE, S.; JIA, Q.; DING, D.; TONG, C.; ZHANG, X.O.; GAO, Q.; SHUAI, L. Capture of Totipotency in Mouse Embryonic Stem Cells in the Absence of Pdzk1. Adv Sci (Weinh), v.12, n.6, p.e2408852, 2025. doi: 10.1002/advs.202408852. DOI: https://doi.org/10.1002/advs.202408852
ZHOU, Y.; BASU, S.; LAUE, E.; SESHIA, A.A. Single cell studies of mouse embryonic stem cell (mESC) differentiation by electrical impedance measurements in a microfluidic device. Biosens Bioelectronics, v.81, p.249-258, 2016. doi: 10.1016/j.bios.2016.02.069. DOI: https://doi.org/10.1016/j.bios.2016.02.069
ZIEGLER, C. Cell-based biosensors. Fresenius' Journal of Analytical Chemistry, v.366, n.6-7, p.552-9, 2000. doi: 10.1007/s002160051550. DOI: https://doi.org/10.1007/s002160051550
Descargas
Publicado
Número
Sección
Licencia
Derechos de autor 2025 Enrico Jardim Clemente Santos, Angela Mazzeo
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Authors who publish in this journal agree to the following terms:
Authors retain copyright and grant the journal the right of first publication, with the work simultaneously licensed under the Creative Commons Attribution License, which permits the sharing of the work with proper acknowledgment of authorship and initial publication in this journal;
Authors are authorized to enter into separate, additional agreements for the non-exclusive distribution of the version of the work published in this journal (e.g., posting in an institutional repository or publishing it as a book chapter), provided that authorship and initial publication in this journal are properly acknowledged, and that the work is adapted to the template of the respective repository;
Authors are permitted and encouraged to post and distribute their work online (e.g., in institutional repositories or on their personal websites) at any point before or during the editorial process, as this may lead to productive exchanges and increase the impact and citation of the published work (see The Effect of Open Access);
Authors are responsible for correctly providing their personal information, including name, keywords, abstracts, and other relevant data, thereby defining how they wish to be cited. The journal’s editorial board is not responsible for any errors or inconsistencies in these records.
PRIVACY POLICY
The names and email addresses provided to this journal will be used exclusively for the purposes of this publication and will not be made available for any other purpose or to third parties.
Note: All content of the work is the sole responsibility of the author and the advisor.
