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Language: English

Conflict of Interest: In relation to this article, we declare that there is no conflict of interest.

Publication history: Received September 26, 2022
Revised December 26, 2022
Accepted December 29, 2022

Acknowledgements: This work was supported by the Samsung Research Funding & Incubation Center of Samsung Electronics under project number SRFC-TC2003-03.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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A microfluidic platform for simulating stem cell migration using in vivo-like gradients of stem cell mobilizer

Jin Kim^1† Jinyoung Kim^1† Hyun-Ji Park^{1 2†} Eun Je Jeon¹ Seung-Woo Cho^1†

¹Department of Biotechnology, Yonsei University, Seoul 03722, Korea ²Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea

seungwoocho@yonsei.ac.kr

Korean Journal of Chemical Engineering, April 2023, 40(4), 903-909(7), 10.1007/s11814-023-1390-6

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Abstract

Stem cell mobilization by cytokines and peptide drugs contributes to wound healing in injured tissues. Owing to the short half-life of cytokines and short peptides in vivo, precisely predicting the in vivo therapeutic efficacy of stem cell mobilizers is difficult using current in vitro models. To address this problem, we developed a multichannel microfluidic device with diffusion barriers to recapitulate drug gradients in an in vivo-like environment. We investigated the effects of Substance P (SP), a stem cell mobilizer, on the migration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) in the microfluidic chip, which replicated in vivo drug gradients. Simulations of SP concentration indicated that our microfluidic chip established SP gradients in migration channels, unlike the existing scratch model for cell migration assays. The scratch model did not distinguish the effects of SP with a short half-life and PEGylated SP with an extended half-life on BM-MSC migration, whereas the microfluidic system demonstrated that PEG-SP affected BM-MSC migration more than SP. Furthermore, the microfluidic chip allowed accurate quantification of the distance and direction of BM-MSC migration. Our microfluidic system could be useful for the precise evaluation of drugs associated with cell migration and mobilization

Keywords

Microfluidic Chip Cell Migration Stem Cell Mobilization Substance P Drug Gradient

References

1. T. H. Kao, Y. C. Lin, P. H. Lee, C. W. Lin, P. H. Chen, T. S. Tai, Y. C.Chang, M. H. Chou, C. Y. Chang and C. K. Sun, Tissue. Eng. Regen.Med., 17, 671 (2020).
2. S. Kim, O. J. Kwon, J. Lee, J. Kim, T.-h. Kim and K. Kim, Biotechnol. Bioprocess Eng., 26, 335 (2021).
3. Y.-C.Yang, Q.-H. Hong, K. F. Lei and A. C.-Y. Chen, BioChip J., 15,243 (2021).
4. J. Kim, N. K. Kim, S. R. Park and B. H. Choi, Tissue. Eng. Regen.Med., 16, 59 (2019).
5. I. Petit, M. Szyper-Kravitz, A. Nagler, M. Lahav, A. Peled, L. Habler,T. Ponomaryov, R. S. Taichman, F. Arenzana-Seisdedos, N. Fujii, J.Sandbank, D. Zipori and T. Lapidot, Nat. Immunol., 3, 687 (2002).
6. C. Savitri, J. W. Kwon, V. Drobyshava, S. S. Ha and K. Park, Tissue.Eng. Regen. Med., 19, 617 (2022).
7. L. To, D. Haylock, P. Simmons and C. Juttner, Blood, 89, 2233(1997).
8. E. Baez-Jurado, O. Hidalgo-Lanussa, G. Guio-Vega, G. M. Ashraf, V.Echeverria, G. Aliev and G. E. Barreto, Mol. Neurobiol., 55, 5377(2018).
9. M. L. De Ieso and J. V. Pei, Biosci. Rep., 38, BSR20180698 (2018).
10. O. K. Hwang, Y. W. Noh, J. T. Hong and J. W. Lee, Tissue. Eng. Regen.Med., 17, 335 (2020).
11. S. S. Omar Zaki, L. Kanesan, M. Y. D. Leong and S. Vidyadaran,Cell. Biol. Int., 43, 1201 (2019).
12. X. Tian, L. Zhang, Y. Jiao, J. Chen, Y. Shan and W. Yang, J. Cell. Biochem., 120, 3765 (2019).
13. G. Shabestani Monfared, P. Ertl and M. Rothbauer, Pharmaceutics, 13, 793 (2021).
14. K. P. Goetsch and C. U. Niesler, Anal. Biochem., 411, 158 (2011).
15. M. H. Olsen, G. M. Hjorto, M. Hansen, O. Met, I. M. Svane and N. B. Larsen, Lab Chip, 13, 4800 (2013).
16. N. L. Jeon, H. Baskaran, S. K. W. Dertinger, G. M. Whitesides, L.Van De Water and M. Toner, Nat. Biotechnol., 20, 826 (2002).
17. Y. Shin, S. Han, J. S. Jeon, K. Yamamoto, I. K. Zervantonakis, R.Sudo, R. D. Kamm and S. Chung, Nat. Protoc., 7, 1247 (2012).
18. H. S. Hong, J. Lee, E. Lee, Y. S. Kwon, E. Lee, W. Ahn, M. H. Jiang,J. C. Kim and Y. Son, Nat. Med., 15, 425 (2009).
19. H.-J. Park, S. Kim, E. J. Jeon, I.-T. Song, H. Lee, Y. Son, H. S. Hong and S.-W. Cho, J. Ind. Eng. Chem., 78, 396 (2019).
20. G. Andersson, L. J. Backman, A. Scott, R. Lorentzon, S. Forsgren and P. Danielson, Br. J. Sports Med., 45, 1017 (2011).
21. R. A. Skidgel, S. Engelbrecht, A. R. Johnson and E. G. Erdös, Peptides, 5, 769 (1984).
22. J. J. Bowden, A. M. Garland, P. Baluk, P. Lefevre, E. F. Grady, S. R.Vigna, N. W. Bunnett and D. M. McDonald, Proc. Natl. Acad Sci.,91, 8964 (1994).
23. H. J. Park, R. Kuai, E. J. Jeon, Y. Seo, Y. Jung, J. J. Moon, A. Schwendeman and S. W. Cho, Biomaterials, 161, 69 (2018).
24. C. Garret, A. Carruette, V. Fardin, S. Moussaoui, J.-F. Peyronel, O.J.-C. Blanchard and P. M. Laduron, Proc. Natl. Acad Sci., 88, 10208(1991).
25. K. Ikeda, K. Miyata, A. Orita, H. Kubota, T. Yamada and K. Tomioka, Neurosci. Lett., 198, 103 (1995).
26. H. Moghadas, M. S. Saidi, N. Kashaninejad and N. T. Nguyen, Drug Deliv. Transl. Res., 8, 830 (2018).
27. U. L. Khatun, A. Gayen and C. Mukhopadhyay, Glycoconj J., 31,435 (2014).
28. W. H. Fissell, C. L. Hofmann, N. Ferrell, L. Schnell, A. Dubnisheva,A. L. Zydney, P. D. Yurchenco and S. Roy, Am. J. Physiol. Renal.Physiol., 297, F1092 (2009).
29. D. Van den Brand, L. F. Massuger, R. Brock and W. P. Verdurmen,Bioconjug. Chem., 28, 846 (2017).
30. J. S. Suk, Q. Xu, N. Kim, J. Hanes and L. M. Ensign, Adv. Drug Deliv. Rev., 99, 28 (2016).
31. C. S. Fishburn, J. Pharm. Sci., 97, 4167 (2008)
32. R. Visentin, G. Pasut, F. M. Veronese and U. Mazzi, Bioconjug.Chem., 15, 1046 (2004).
33. T. Wymore and T. C. Wong, Biophys. J., 76, 1213 (1999).
34. C. Ruan, L. Liu, Y. Lu, Y. Zhang, X. He, X. Chen, Y. Zhang, Q. Chen,Q. Guo, T. Sun and C. Jiang, Acta Pharm. Sin. B, 8, 85 (2018).