Skip to main content
Log in

Biochips for Regenerative Medicine: Real-time Stem Cell Continuous Monitoring as Inferred by High-Throughput Gene Analysis

  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

Regenerative medicine is a novel clinical branch aiming at the cure of diseases by replacement of damaged tissues. The crucial use of stem cells makes this area rich of challenges, given the poorly understood mechanisms of differentiation. One highly needed and yet unavailable technology should allow us to monitor the exact (metabolic) state of stem cells differentiation to maximize the effectiveness of their implant in vivo. This is challenged by the fact that not all relevant metabolites in stem cells differentiation are known and not all metabolites can currently be continuously monitored. To bring advancements in this direction, we propose the enhancement and integration of two available technologies into a general pipeline. Namely, high-throughput biochip for gene expression screening to pre-select the variables that are most likely to be relevant in the identification of the stem cells’ state and low-throughput biochip for continuous monitoring of cell metabolism with highly sensitive carbon nanotubes-based sensors. Intriguingly, additionally to the involvement of multidisciplinary expertise (medicine, molecular biology, computer science, engineering, and physics), this whole query heavily relies on biochips: it starts in fact from the use of high-throughput ones, which output, in turn, becomes the base for the design of low-throughput, highly sensitive biochips. Future research is warranted in this direction to develop and validated the proposed device.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chien, K. R., Domian, I. J., Parker, K. K. (2008). Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science, 322(5907), 1494–1497.

    Article  Google Scholar 

  2. Brown, P. O., & Botstein, D. (1999). Exploring the new world of the genome with dna microarrays. Nature Genetics, 21(1), 33–37.

    Article  Google Scholar 

  3. Holt, R, A., & Jones, S. J. (2008). The new paradigm of flow cell sequencing. Genome Research, 18(6), 839–846.

    Article  Google Scholar 

  4. Wang, Z., Gerstein, M., Snyder, M. (2009). RNA-Seq: A revolutionary tool for transcriptomics. Nature Reviews Genetics, 10(1), 57–63.

    Article  Google Scholar 

  5. Fu, X., Fu, N., Guo, S., Yan, Z., Xu, Y., Hu, H., et al. (2009). Estimating accuracy of RNA-Seq and microarrays with proteomics. BMC Genomics, 10, 161–161.

    Article  Google Scholar 

  6. Bloom, J. S., Khan, Z., Kruglyak, L., Singh, M., Caudy, A. A. (2009). Measuring differential gene expression by short read equencing: Quantitative comparison to 2-channel gene expression microarrays. BMC Genomics, 10, 22.

    Article  Google Scholar 

  7. Ji, H., & Davis, R. W. (2006). Data quality in genomics and microarrays. Nature Biotechnology, 24, 1112–1113.

    Article  Google Scholar 

  8. Poscia, A., Mascini, M., Moscone, D., Luzzana, M., Caramenti, G., Cremonesi, P., et al. (2003). A microdialysis technique for continuous subcutaneous glucose monitoring in diabetic patients (part 1). Biosensors & Bioelectronics, 18(7), 891–898.

    Article  Google Scholar 

  9. Varalli, M., Marelli, G., Maran, A., Bistoni, S., Luzzana, M., Cremonesi, P., et al. (2003). A microdialysis technique for continuous subcutaneous glucose monitoring in diabetic patients (part 2). Biosensors & Bioelectronics, 18(7), 899–905.

    Article  Google Scholar 

  10. Poscia, A., Messeri, D., Moscone, D., Ricci, F., Valgimigli, F. (2005). A novel continuous subcutaneous lactate monitoring system. Biosensors & Bioelectronics, 20(11), 2244–2250.

    Article  Google Scholar 

  11. Boero, C., Carrara, S., Del Vecchio, G., Calza, L., De Micheli, G. (2011). Targeting of multiple metabolites in neural cell monitored by using protein-based carbon nanotubes. Sensors and Actuators, 157(1), 216–224.

    Article  Google Scholar 

  12. Valgimigli, F., Lucarelli, F., Scuffi, C., Morandi, S., Sposato, I. (2010). Evaluating the clinical accuracy of glucomen day: A novel microdialysis-based continuous glucose monitor. Journal of Diabetes Science and Technology, 4(5), 1182–1192.

    Google Scholar 

  13. Carrara, S., Bolomey, L., Boero, C., Cavallini, A., Meurville, E., De Micheli, G., et al. (2011). Single-metabolite bio-nano-sensors and system for remote monitoring in animal model. In IEEE international conference sensors 2011, Limerick.

  14. Bistolas, N., Wollenberger, U., Jung, C., Scheller, F. (2005). Cytochrome p450 biosensors—a review. Biosensors & Bioelectronics, 20(12), 2408–2423.

    Article  Google Scholar 

  15. Carrara, S., Cavallini, A., Erokhin, V., De Micheli, G. (2011). Multi-panel drugs detection in human serum for personalized therapy. Biosensors & Bioelectronics, 26, 3914–3919.

    Article  Google Scholar 

  16. Carrara, S., Shumyantseva, V. V., Archakov, A. I., Samorì, B. (2008). Screen-printed electrodes based on carbon nanotubes and cytochrome p450scc for highly sensitive cholesterol biosensors. Biosensors & Bioelectronics, 24(1), 148–150.

    Article  Google Scholar 

  17. Cavallini, A., De Micheli, G., Carrara, S. (2011). Comparison of three methods of biocompatible multi-walled carbon nanotubes confinement for the development of implantable amperometric ATP biosensors. Sensor Letters (in press).

  18. Mering, C., Huynen, M., Jaeggi, D., Schmidt, S., Bork, P., Snel, B. (2011). STRING: A database of predicted functional associations between proteins. Nucleic Acids Research, 31(1), 258. ISSN 0305-1048.

    Article  Google Scholar 

  19. Jeffery, I. B., Higgins, D. G., Culhane, A. C. (2006). Comparison and evaluation of methods for generating differentially expressed gene lists from microarray data. BMC Bioinformatics, 7, 359–359.

    Article  Google Scholar 

  20. Pirondi, S., Fernández, M., Chen, B. L., Del Vecchio, G., Alessandri, M., Farnedi, A., et al. (2011). Isolation of rat embryonic stem-like cells: A tool for stem cell research and drug discovery. Developmental Dynamics, 240(11), 2482–2494. doi:10.1002/dvdy.22761.

    Article  Google Scholar 

  21. Chan, Y. S., Yang, L., Ng, H. H. (2011). Transcriptional regulatory networks in embryonic stem cells. Progress in Drug Research, 67, 239–252.

    Google Scholar 

  22. Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., Hattori, M. (2004). The kegg resource for deciphering the genome. Nucleic Acids Research, 32(Database issue), 277–280.

    Article  Google Scholar 

  23. Roach, M. L. & McNeish, J. D. (2002). Methods for the isolation and maintenance of murine embryonic stem cells. In K. Turksen (Ed.), Embryonic stem cells: Methods and protocols. NJ: Humana Press Inc. doi:10.1385/1-59259-241-4:1.

    Google Scholar 

  24. Guo, L., Lobenhofer, E. K, Wang, C., Shippy, R., Harris, S. C., Zhang, L., et al. (2006). Rat toxicogenomic study reveals analytical consistency across microarray platforms. Nature Biotechnology, 24(9), 1162–1169. ISSN 1087-0156.

    Article  Google Scholar 

  25. Smyth, G. (2005). Limma: Linear models for microarray data. In Bioinformatics and computational biology solutions using R and bioconductor (pp. 397–420).

  26. Qin, J., Díaz-Cueto, L., Schwarze, J. E, Takahashi, Y., Imai, M., Isuzugawa, K., et al. (2005). Effects of progranulin on blastocyst hatching and subsequent adhesion and outgrowth in the mouse. Biology of Reproduction, 73(3), 434–442.

    Article  Google Scholar 

  27. Wang, L., Schulz, T. C., Sherrer, E. S., Dauphin, D. S., Shin, S., Nelson, A. M., et al. (2007). Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling. Blood, 110(12), 4111–4119.

    Article  Google Scholar 

  28. Li, Y., & Geng, Y. J. (2010). A potential role for insulin-like growth factor signaling in induction of pluripotent stem cell formation. Growth Hormone IGF Research, 20(6), 391–398.

    Article  MathSciNet  MATH  Google Scholar 

  29. Ratajczak, J., Wan, W., Liu, R., Shin, D.-M., Kucia, M., Bartke, A., et al. (2010). Unexpected evidence that chronic IGF-1 deficiency in laron dwarf mice maintains high levels of hematopoietic stem cells (HSCs) in BM—are HSCs gradually depleted from BM with age in an IGF-1 cdependent manner? Implications for the novel effect of caloric restriction on the hematopoietic stem cell compartment and longevity. Blood (ASH Annual Meeting Abstracts), 116(1551).

  30. Sepúlveda, D. E., Andrews, B. A., Papoutsakis, E. T., Asenjo, J. A. (2010). Metabolic flux analysis of embryonic stem cells using three distinct differentiation protocols and comparison to gene expression patterns. Biotechnology Progress, 26(5), 1222–1229.

    Article  Google Scholar 

  31. Yanes, O., Clark, J., Wong, D. M., Patti, G. J., Sánchez-Ruiz, A., Benton, H. P., et al. (2010). Metabolic oxidation regulates embryonic stem cell differentiation. Nature Chemical Biology, 6(6), 411–417.

    Article  Google Scholar 

  32. Filvaroff, E. H., Guillet, S., Zlot, C., Bao, M., Ingle, G., Steinmetz, H. (2002). Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice. Endocrinology, 143(9), 3681–3690.

    Article  Google Scholar 

  33. Dallmann, R., Touma, C., Palme, R., Albrecht, U., Steinlechner, S. (2006). Impaired daily glucocorticoid rhythm in per1 (brd) mice. Journal of Comparative Physiology A, Sensory, Neural, and Behavioral Physiology, 192(7), 769–775.

    Article  Google Scholar 

  34. Ando, H., Takamura, T., Matsuzawa-Nagata, N., Shima, K. R., Eto, T., Misu, H., et al. (2009). Clock gene expression in peripheral leucocytes of patients with type 2 diabetes. Diabetologia, 52(2), 329–335.

    Article  Google Scholar 

  35. Krapivner, S., Chernogubova, E., Ericsson, M., Ahlbeck-Glader, C., Hamsten, A., van ’t Hooft, F. M. (2007). Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration. Diabetologia, 50(1), 94–102.

    Article  Google Scholar 

  36. Nebert, W. D., Dalton, P. T. (2006). The role of cytochrome p450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nature Reviews Cancer, 6, 947–960.

    Article  Google Scholar 

  37. Sarath Babu, V. R., Patra, N. G., Karanth, S., Kumar, M. A., Thakur, M. S. (2007). Development of a biosensor for caffeine. Analytica Chimica Acta, 582(2), 329–334.

    Article  Google Scholar 

  38. Saitoh, H., Namatame, Y., Hirano, A., Sugawara, M. (2004). An excised patch membrane sensor for arachidonic acid released in mouse hippocampal slices under stimulation of l-glutamate. Analytical Biochemistry, 329(2), 163–172.

    Article  Google Scholar 

  39. Turner, S. K., Daff, K. L., Chapman, S. N., Holt, R. A., Govindaraj, S., Poulos, T. L., et al. (1997). Redox control of the catalytic cycle of flavocytochrome p-450 BM3. Biochemistry, 36(45), 13816–13823.

    Article  Google Scholar 

  40. Navet, W. R., Alberici, L. C., Douette, P., Sluse-Goffart, C. M., Sluse, F. E., Vercesi, A. E. (2004) Redox state of endogenous coenzyme q modulates the inhibition of linoleic acid-induced uncoupling by guanosine triphosphate in isolated skeletal muscle mitochondria. Journal of Bioenergetics and Biomembranes, 36(5), 493–502.

    Article  Google Scholar 

  41. Luo, Y.-C., Do, J.-S., Liu, C.-C. (2006). An amperometric uric acid biosensor based on modified Ir-C electrode. Biosensors and Bioelectronics, 22, 482–488.

    Article  Google Scholar 

  42. Jobst, I. G., Aschauer, E., Svasek, P., Varahram, M., Urban, G. (1995). Miniaturized thin film glutamate and glutamine biosensors. Biosensors and Bioelectronics, 10, 527–532.

    Article  Google Scholar 

  43. Guiducci, C., & Nardini, C. (2008). High parallelism, portability and broad accessibility: Technologies for genomics. ACM Journal on Emerging Technologies in Computing Systems, 4(1),1–39 (Article 3).

    Article  Google Scholar 

  44. Fronza, R., Tramonti, M., Atchley, W. R., Nardini, C. (2011). Joint analysis of transcriptional and post- transcriptional brain tumor data: Searching for emergent properties of cellular systems. BMC Bioinformatics, 12, 86–86.

    Article  Google Scholar 

Download references

Acknowledgement

This work is funded by the Sino-Swiss Science and Technology Cooperation Project (grant no.: GJHZ0911 on the Chinese side and grant no.: IZLCZ2 123967 on the Swiss side).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christine Nardini.

Additional information

L. Zhu and G. del Vecchio contributed equally to this work.

This work is funded by the Sino-Swiss Science and Technology Cooperation Project (grant no.: GJHZ0911 on the Chinese side and grant no.: IZLCZ2 123967 on the Swiss side).

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

(PDF 254 KB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, L., del Vecchio, G., de Micheli, G. et al. Biochips for Regenerative Medicine: Real-time Stem Cell Continuous Monitoring as Inferred by High-Throughput Gene Analysis. BioNanoSci. 1, 183–191 (2011). https://doi.org/10.1007/s12668-011-0028-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12668-011-0028-z

Keywords

Navigation