Designing magnetic microcapsules for cultivation and differentiation of stem cell spheroids.


Journal

Microsystems & nanoengineering
ISSN: 2055-7434
Titre abrégé: Microsyst Nanoeng
Pays: England
ID NLM: 101695458

Informations de publication

Date de publication:
12 Sep 2024
Historique:
received: 15 02 2024
accepted: 05 06 2024
revised: 03 05 2024
medline: 12 9 2024
pubmed: 12 9 2024
entrez: 11 9 2024
Statut: epublish

Résumé

Human pluripotent stem cells (hPSCs) represent an excellent cell source for regenerative medicine and tissue engineering applications. However, there remains a need for robust and scalable differentiation of stem cells into functional adult tissues. In this paper, we sought to address this challenge by developing magnetic microcapsules carrying hPSC spheroids. A co-axial flow-focusing microfluidic device was employed to encapsulate stem cells in core-shell microcapsules that also contained iron oxide magnetic nanoparticles (MNPs). These microcapsules exhibited excellent response to an external magnetic field and could be held at a specific location. As a demonstration of utility, magnetic microcapsules were used for differentiating hPSC spheroids as suspension cultures in a stirred bioreactor. Compared to standard suspension cultures, magnetic microcapsules allowed for more efficient media change and produced improved differentiation outcomes. In the future, magnetic microcapsules may enable better and more scalable differentiation of hPSCs into adult cell types and may offer benefits for cell transplantation.

Identifiants

pubmed: 39261472
doi: 10.1038/s41378-024-00747-9
pii: 10.1038/s41378-024-00747-9
doi:

Types de publication

Journal Article

Langues

eng

Pagination

127

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : DK107255

Informations de copyright

© 2024. The Author(s).

Références

Cohen, D. E. & Melton, D. Turning straw into gold: directing cell fate for regenerative medicine. Nat. Rev. Genet. 12, 243–252 (2011).
doi: 10.1038/nrg2938
Geary, L. & LaBonne, C. FGF mediated MAPK and PI3K/Akt Signals make distinct contributions to pluripotency and the establishment of neural crest. Elife 7, e33845 (2018).
doi: 10.7554/eLife.33845
Gordeeva, O. TGFβ family signaling pathways in pluripotent and teratocarcinoma stem cells' fate decisions: balancing between self-renewal, differentiation, and cancer. Cells 8, 1500 (2019).
doi: 10.3390/cells8121500
Serra, M., Brito, C., Correia, C. & Alves, P. M. Process engineering of human pluripotent stem cells for clinical application. Trends Biotechnol. 30, 350–359 (2012).
doi: 10.1016/j.tibtech.2012.03.003
Lee, B. et al. Cell culture process scale-up challenges for commercial-scale manufacturing of allogeneic pluripotent stem cell products. Bioengineering 9, 92 (2022).
doi: 10.3390/bioengineering9030092
Simaria, A. S. et al. Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies. Biotechnol. Bioeng. 111, 69–83 (2014).
doi: 10.1002/bit.25008
Kropp, C., Massai, D. & Zweigerdt, R. Progress and challenges in large-scale expansion of human pluripotent stem cells. Process Biochem 59, 244–254 (2017).
doi: 10.1016/j.procbio.2016.09.032
Kehoe, D. E., Jing, D., Lock, L. T. & Tzanakakis, E. S. Scalable stirred-suspension bioreactor culture of human pluripotent stem cells. Tissue Eng. Part A 16, 405–421 (2010).
doi: 10.1089/ten.tea.2009.0454
Rodrigues, C. A. V., Fernandes, T. G., Diogo, M. M., da Silva, C. L. & Cabral, J. M. S. Stem cell cultivation in bioreactors. Biotechnol. Adv. 29, 815–829 (2011).
doi: 10.1016/j.biotechadv.2011.06.009
Wang, Y. et al. Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions. Stem Cell Res. 11, 1103–1116 (2013).
doi: 10.1016/j.scr.2013.07.011
Sargent, C. Y. et al. Hydrodynamic modulation of embryonic stem cell differentiation by rotary orbital suspension culture. Biotechnol. Bioeng. 105, 611–626 (2010).
doi: 10.1002/bit.22578
Chen, V. C. et al. Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells. Stem Cell Res. 15, 365–375 (2015).
doi: 10.1016/j.scr.2015.08.002
Mollet, M. et al. Bioprocess equipment: characterization of energy dissipation rate and its potential to damage cells. Biotechnol. Prog. 20, 1437–1448 (2004).
doi: 10.1021/bp0498488
Gareau, T. et al. Shear stress influences the pluripotency of murine embryonic stem cells in stirred suspension bioreactors. J. Tissue Eng. Regen. Med. 8, 268–278 (2014).
doi: 10.1002/term.1518
Wolfe, R. P. & Ahsan, T. T. Shear stress during early embryonic stem cell differentiation promotes hematopoietic and endothelial phenotypes. Biotechnol. Bioeng. 110, 1231–1242 (2013).
Wolfe, R. P., Leleux, J., Nerem, R. M. & Ahsan, T. Effects of shear stress on germ lineage specification of embryonic stem cells. Integr. Biol. 4, 1263–1273 (2012).
doi: 10.1039/c2ib20040f
Kraehenbuehl, T. P., Langer, R. & Ferreira, L. S. Three-dimensional biomaterials for the study of human pluripotent stem cells. Nat. Methods 8, 731–736 (2011).
doi: 10.1038/nmeth.1671
Allen, A. B., Priddy, L. B., Li, M.-T. A. & Guldberg, R. E. Functional augmentation of naturally-derived materials for tissue regeneration. Ann. Biomed. Eng. 43, 555–567 (2015).
doi: 10.1007/s10439-014-1192-4
Belair, D. G., Le, N. N. & Murphy, W. L. Design of growth factor sequestering biomaterials. Chem. Commun. 50, 15651–15668 (2014).
doi: 10.1039/C4CC04317K
Nichol, J. W. et al. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31, 5536–5544 (2010).
doi: 10.1016/j.biomaterials.2010.03.064
Badenes, S. M., Fernandes, T. G., Rodrigues, C. A. V., Diogo, M. M. & Cabral, J. M. S. Microcarrier-based platforms for in vitro expansion and differentiation of human pluripotent stem cells in bioreactor culture systems. J. Biotechnol. 234, 71–82 (2016).
doi: 10.1016/j.jbiotec.2016.07.023
Fan, Y., Hsiung, M., Cheng, C. & Tzanakakis, E. S. Facile engineering of xeno-free microcarriers for the scalable cultivation of human pluripotent stem cells in stirred suspension. Tissue Eng. Part A 20, 588–599 (2014).
Badenes, S. M. et al. Long-term expansion of human induced pluripotent stem cells in a microcarrier-based dynamic system: long-term expansion of hiPS cells on microcarriers. J. Chem. Technol. Biotechnol. 92, 492–503 (2017).
doi: 10.1002/jctb.5074
Hernández, R. M., Orive, G., Murua, A. & Pedraz, J. L. Microcapsules and microcarriers for in situ cell delivery. Adv. Drug Deliv. Rev. 62, 711–730 (2010).
doi: 10.1016/j.addr.2010.02.004
Agarwal, P. et al. One-step microfluidic generation of pre-hatching embryo-like core-shell microcapsules for miniaturized 3D culture of pluripotent stem cells. Lab Chip. 13, 4525–4533 (2013).
doi: 10.1039/c3lc50678a
Xu, J. et al. Handheld microfluidic filtration platform enables rapid, low‐cost, and robust self‐testing of SARS‐CoV‐2 virus. Small 17, 2102219 (2021).
Maguire, T., Novik, E., Schloss, R. & Yarmush, M. Alginate-PLL microencapsulation: effect on the differentiation of embryonic stem cells into hepatocytes. Biotechnol. Bioeng. 93, 581–591 (2006).
doi: 10.1002/bit.20748
Barminko, J. et al. Encapsulated mesenchymal stromal cells for in vivo transplantation. Biotechnol. Bioeng. 108, 2747–2758 (2011).
doi: 10.1002/bit.23233
Kinney, M. A., Sargent, C. Y. & McDevitt, T. C. The multiparametric effects of hydrodynamic environments on stem cell culture. Tissue Eng. Part B Rev. 17, 249–262 (2011).
doi: 10.1089/ten.teb.2011.0040
Gwon, K. et al. Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor. Bioact. Mater. 28, 183–195 (2023).
Dhawan, A. et al. Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children. J. Hepatol. 72, 877–884 (2020).
doi: 10.1016/j.jhep.2019.12.002
Tuch, B. E. et al. Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 32, 1887–1889 (2009).
doi: 10.2337/dc09-0744
Zhao, S. et al. Coaxial electrospray of liquid core-hydrogel shell microcapsules for encapsulation and miniaturized 3D culture of pluripotent stem cells. Integr. Biol. 6, 874–884 (2014).
doi: 10.1039/c4ib00100a
Seo, K. D., Kim, D. S. & Sánchez, S. Fabrication and applications of complex-shaped microparticles via microfluidics. Lab Chip. 15, 3622–3626 (2015).
doi: 10.1039/C5LC90091C
Dendukuri, D. & Doyle, P. S. The synthesis and assembly of polymeric microparticles using microfluidics. Adv. Mater. 21, 4071–4086 (2009).
doi: 10.1002/adma.200803386
Yeh, J. et al. Micromolding of shape-controlled, harvestable cell-laden hydrogels. Biomaterials 27, 5391–5398 (2006).
doi: 10.1016/j.biomaterials.2006.06.005
Gwon, K., Hong, H. J., Gonzalez-Suarez, A. M., Stybayeva, G. & Revzin, A. Microfluidic fabrication of core-shell microcapsules carrying human pluripotent stem cell spheroids. J. Vis. Exp. 176, e62944 (2021).
Siltanen, C. et al. One step fabrication of hydrogel microcapsules with hollow core for assembly and cultivation of hepatocyte spheroids. Acta Biomater. 50, 428–436 (2017).
doi: 10.1016/j.actbio.2017.01.010
Fattahi, P. et al. Core-shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor. Sci. Rep. 11, 7177 (2021).
doi: 10.1038/s41598-021-85786-2
Ceylan, H., Giltinan, J., Kozielski, K. & Sitti, M. Mobile microrobots for bioengineering applications. Lab Chip 17, 1705–1724 (2017).
doi: 10.1039/C7LC00064B
Ceylan, H. et al. 3D printed personalized magnetic micromachines from patient blood-derived biomaterials. Sci. Adv. 7, eabh0273 (2021).
doi: 10.1126/sciadv.abh0273
Yasa, I. C., Tabak, A. F., Yasa, O., Ceylan, H. & Sitti, M. 3D‐printed microrobotic transporters with recapitulated stem cell niche for programmable and active cell delivery. Adv. Funct. Mater. 29, 1808992 (2019).
doi: 10.1002/adfm.201808992
Kamei, N. et al. The safety and efficacy of magnetic targeting using autologous mesenchymal stem cells for cartilage repair. Knee Surg. Sports Traumatol. Arthrosc. 26, 3626–3635 (2018).
doi: 10.1007/s00167-018-4898-2
Vaněček, V. et al. Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury. Int. J. Nanomed. 7, 3719–3730 (2012).
doi: 10.2147/IJN.S32824
Kamei, G. et al. Articular cartilage repair with magnetic mesenchymal stem cells. Am. J. Sports Med. 41, 1255–1264 (2013).
doi: 10.1177/0363546513483270
Koudan, E. V. et al. Magnetic patterning of tissue spheroids using polymer microcapsules containing iron oxide nanoparticles. ACS Biomater. Sci. Eng. 7, 5206–5214 (2021).
doi: 10.1021/acsbiomaterials.1c00805
Dai, R. et al. Improved neural differentiation of stem cells mediated by magnetic nanoparticle-based biophysical stimulation. J. Mater. Chem. B 7(26), 4161–4168 (2019).
doi: 10.1039/C9TB00678H
Cho, S. et al. Tension exerted on cells by magnetic nanoparticles regulates differentiation of human mesenchymal stem cells. Biomater. Adv. 139, 213028 (2022).
doi: 10.1016/j.bioadv.2022.213028
Gwon, K. et al. Bioactive hydrogel microcapsules for guiding stem cell fate decisions by release and reloading of growth factors. Bioact. Mater. 15, 1–14 (2022).
Foster, E. et al. Heparin hydrogel sandwich cultures of primary hepatocytes. Eur. Polym. J. 72, 726–735 (2015).
doi: 10.1016/j.eurpolymj.2014.12.033
de Hoyos-Vega, J. M., Hong, H. J., Loutherback, K., Stybayeva, G. & Revzin, A. A microfluidic device for long‐term maintenance of organotypic liver cultures. Adv. Mater. Technol. 8, 2201121 (2023).
doi: 10.1002/admt.202201121
Guild, J. et al. Embryonic stem cells cultured in microfluidic chambers take control of their fate by producing endogenous signals including LIF. Stem Cells 34, 1501–1512. (2016).
doi: 10.1002/stem.2324
Abbott, J. J., Diller, E. & Petruska, A. J. Magnetic methods in robotics. Annu. Rev. Control Robot. Auton. Syst. 3, 57–90 (2020).
doi: 10.1146/annurev-control-081219-082713
Kim, J. et al. Programming magnetic anisotropy in polymeric microactuators. Nat. Mater. 10, 747–752 (2011).
doi: 10.1038/nmat3090
Ceylan, H. et al. 3D-printed biodegradable microswimmer for theranostic cargo delivery and release. ACS Nano 13, 3353–3362 (2019).
doi: 10.1021/acsnano.8b09233
Choi, D. et al. Coating bioactive microcapsules with tannic acid enhances the phenotype of the encapsulated pluripotent stem cells. ACS Appl. Mater. Interfaces 14, 27274–27286 (2022).
doi: 10.1021/acsami.2c06783
Pagliuca, F. W. et al. Generation of functional human pancreatic β cells in vitro. Cell 159, 428–439. (2014).
doi: 10.1016/j.cell.2014.09.040

Auteurs

Kihak Gwon (K)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. khgwon@knu.ac.kr.
Department of Biofibers and Biomaterials Science, Kyungpook National University, Daegu, Republic of Korea. khgwon@knu.ac.kr.

Ether Dharmesh (E)

Department of Biomedical Engineering, Saint Louis University, St. Louis, MO, USA.

Kianna M Nguyen (KM)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

Anna Marie R Schornack (AMR)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

Jose M de Hoyos-Vega (JM)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

Hakan Ceylan (H)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Scottsdale, AZ, USA.

Gulnaz Stybayeva (G)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

Quinn P Peterson (QP)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

Alexander Revzin (A)

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. revzin.alexander@mayo.edu.

Classifications MeSH