Highly Efficient and Rapid Neural Differentiation of Mouse Embryonic Stem Cells Based on Retinoic Acid Encapsulated Porous Nanoparticle
Abstract
An improved cell conversion strategy for neural differentiation of mouse embryonic stem (mES) cells is developed by incorporating functionalized mesoporous silica nanoparticle (MSN) as an efficient delivery carrier of retinoic acid (RA), which is a pleiotropic factor required for initiation of neural differentiation. Traditional RA-mediated neural differentiation methods required either preactivation of the cells to the differentiating state by embryoid body (EB) formation or repetitive treatment of the differentiation factor. Our modified cell conversion system involves only singular treatment of the RA/MSN complex, which simplified the whole process and accelerated neural induction to be finished within 6 days with high quality. With our new method, neural cells were successfully derived from mES cells with stable expression of neurite marker gene.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In physical entrapment, RA is captured during nanoparticle formation or in the pores of the nanoparticles.
“Concerning physical entrapment, RA is captured during nanoparticle formation57,58 or in the pores of the nanoparticles59.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [59]
Cites
Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture
Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003) · Nature Biotechnology · doi:10.1038/nbt780 · Cited by 1,504 · see citing works
Embryonic Stem Cells Express Neuronal Properties in Vitro
Bain, G., Kitchens, D. L., Yao, M., Huettner, J. E., & Gottlieb, D. I. (1995) · Developmental Biology · doi:10.1006/dbio.1995.1085 · Cited by 1,168 · see citing works
In vitro differentiation of embryonic stem cells into glial cells and functional neurons
Fraichard, A., Chassande, O., Bilbaut, G., Dehay, C., Savatier, P., & Samarut, J. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.10.3181 · Cited by 420 · see citing works
Kim, M., Na, H., Kim, Y., Ryoo, S., Cho, H. S., Lee, K. E., Jeon, H., Ryoo, R., & Min, D. (2011) · ACS Nano · doi:10.1021/nn103130q · Cited by 364 · see citing works
Self-citationStrübing, C., Ahnert‐Hilger, G., Shan, J., Wiedenmann, B. J., Hescheler, J., & Wobus, A. M. (1995) · Mechanisms of Development · doi:10.1016/0925-4773(95)00446-8 · Cited by 360 · see citing works
Okada, Y., Shimazaki, T., Sobue, G., & Okano, H. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.07.038 · Cited by 333 · see citing works
Solubility of retinoids in water
Szuts, E. Z., & Harosi, F. I. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90482-x · Cited by 223 · see citing works
Efficient Functional Delivery of siRNA using Mesoporous Silica Nanoparticles with Ultralarge Pores
Na, H., Kim, M., Park, K., Ryoo, S., Lee, K. E., Jeon, H., Ryoo, R., Hyeon, C., & Min, D. (2012) · Small · doi:10.1002/smll.201200028 · Cited by 180 · see citing works
Self-citationNerve growth factor acts via retinoic acid synthesis to stimulate neurite outgrowth
Corcoran, J. P. T., & Maden, M. (1999) · Nature Neuroscience · doi:10.1038/7214 · Cited by 137 · see citing works
Corcoran, J. P. T., Shroot, B., Pizzey, J. A., & Maden, M. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.14.2567 · Cited by 137 · see citing works
Retinoic acid receptor β2 and neurite outgrowth in the adult mouse spinal cord in vitro
Corcoran, J. P. T., So, P.-L., Barber, R. D., Vincent, K. J., Mazarakis, N. D., Mitrophanous, K. A., Kingsman, S. M., & Maden, M. (2002) · Journal of Cell Science · doi:10.1242/jcs.00046 · Cited by 107 · see citing works
Maia, J., Santos, T., Aday, S., Agasse, F., Cortes, L., Malva, J. O., Bernardino, L., & Ferreira, L. (2011) · ACS Nano · doi:10.1021/nn101724r · Cited by 99 · see citing works
Direct cellular delivery of human proteasomes to delay tau aggregation
Han, D. H., Na, H., Choi, W. H., Lee, J. H., Kim, Y. K., Won, C., Lee, S., Kim, K. P., Kuret, J., Min, D., et al. (2014) · Nature Communications · doi:10.1038/ncomms6633 · Cited by 97 · see citing works
Self-citationIn vitro Differentiation of Mouse Embryonic Stem (mES) Cells Using the Hanging Drop Method
Wang, X., & Yang, P. C.-M. (2008) · Journal of Visualized Experiments · doi:10.3791/825 · Cited by 96 · see citing works
Santos, T., Ferreira, R., Maia, J., Agasse, F., Xapelli, S., Cortes, L., Bragança, J., Malva, J. O., Ferreira, L., & Bernardino, L. (2012) · ACS Nano · doi:10.1021/nn304541h · Cited by 92 · see citing works
Seo, H. I., Cho, A., Jang, J., Kim, D., Cho, S., & Chung, B. G. (2015) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2015.05.008 · Cited by 48 · see citing works
Retinoic acid stability in stem cell cultures
Sharow, K. A., Temkin, B., & Asson–Batres, M. A. (2012) · The International Journal of Developmental Biology · doi:10.1387/ijdb.113378ks · Cited by 34 · see citing works
Retinoic acid promotes neural conversion of mouse embryonic stem cells in adherent monoculture
Xu, J., Wang, H., Liang, T., Cai, X., Rao, X., Huang, Z., & Sheng, G. (2011) · Molecular Biology Reports · doi:10.1007/s11033-011-0800-8 · Cited by 27 · see citing works
Ku, B., Kim, J.-E., Chung, B. H., & Chung, B. G. (2013) · Langmuir · doi:10.1021/la4015543 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine
Ferreira, R., Napoli, J., Enver, T., Bernardino, L., & Ferreira, L. (2020) · Nature Communications · doi:10.1038/s41467-020-18042-2 · Cited by 138 · see citing works
Wei, M., Yang, Z., Li, S., & Le, W. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s395010 · Cited by 54 · see citing works
Shin, H., Kang, S., Won, C., & Min, D. (2023) · ACS Nano · doi:10.1021/acsnano.3c06733 · Cited by 49 · see citing works
Self-citationKang, S., Kim, J., Ahn, M., Kim, J., Heo, M.-G., Min, D., & Won, C. (2020) · Nanoscale · doi:10.1039/c9nr10305h · Cited by 39 · see citing works
Self-citationNanotechnology-Driven Cell-Based Therapies in Regenerative Medicine
Alzate‐Correa, D., Lawrence, W. R., Salazar‐Puerta, A. I., Higuita‐Castro, N., & Gallego‐Perez, D. (2022) · The AAPS Journal · doi:10.1208/s12248-022-00692-3 · Cited by 33 · see citing works
Protocol for mouse adult neural stem cell isolation and culture
Ahmed, A. K. M. A., Isaksen, T. J., & Yamashita, T. (2021) · STAR Protocols · doi:10.1016/j.xpro.2021.100522 · Cited by 29 · see citing works
Dual Pathway for Promotion of Stem Cell Neural Differentiation Mediated by Gold Nanocomposites
Zhang, S., Hang, Y., Wu, J., Tang, Z., Li, X., Zhang, S., Wang, L., Brash, J. L., & Chen, H. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b22258 · Cited by 27 · see citing works
Nanoparticle-Functionalized Organoid-on-a-Chip Systems for Biomedical Applications
Lee, M.-J., Lee, S., Kim, S., Shin, M., Lee, S., & Choi, J. (2025) · BioChip Journal · doi:10.1007/s13206-025-00231-0 · Cited by 21 · see citing works
Self-citationGarg, S., Jana, A., Khan, J., Gupta, S., Roy, R., Gupta, V., & Ghosh, S. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c07694 · Cited by 16 · see citing works
The Story of Nanoparticles in Differentiation of Stem Cells into Neural Cells
Asgari, V., Landarani‐Isfahani, A., Salehi, H., Amirpour, N., Hashemibeni, B., Rezaei, S., & Bahramian, H. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02900-7 · Cited by 16 · see citing works
Koo, D.-J., Choi, J., Ahn, M., Ahn, B. H., Min, D., & Kim, S. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00263 · Cited by 15 · see citing works
Self-citationThe effect of nanomaterials on embryonic stem cell neural differentiation: a systematic review
Darehbagh, R. R., Mahmoodi, M., Amini, N., Babahajiani, M., Allavaisie, A., & Moradi, Y. (2023) · European journal of medical research · doi:10.1186/s40001-023-01546-0 · Cited by 14 · see citing works
A Novel Cell Penetrating Peptide for the Differentiation of Human Neural Stem Cells
Ma, W., Jin, G., Gehret, P. M., Chada, N. C., & Suh, W. H. (2018) · Biomolecules · doi:10.3390/biom8030048 · Cited by 13 · see citing works
Tang, H., Wang, J., Yu, L., Zhang, S., He, Y., Li, X., Brash, J. L., Wang, L., & Chen, H. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c22736 · Cited by 13 · see citing works
Nanoengineered Endocytic Biomaterials for Stem Cell Therapy
Wang, Y., Sun, C., Liu, Z., Zhang, S., Gao, K., Yi, F., Zhou, W., & Liu, H. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202410714 · Cited by 11 · see citing works
Li, T., Liu, X., Yang, B., Wang, Z., Chen, Y., Jin, X., & Shen, C. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.03.004 · Cited by 11 · see citing works
Karimi‐Soflou, R., Karkhaneh, A., & Shabani, I. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.213056 · Cited by 11 · see citing works
Yu, F., Cheng, S., Lei, J., Hang, Y., Liu, Q., Wang, H., & Yuan, L. (2020) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2020.1767375 · Cited by 10 · see citing works
Neuronal differentiation and tissue engineering strategies for central nervous system injury repair
Xia, Z., Zhang, J., Ren, N., Wang, S., Zhang, C., Malek, N. A. N. N., Kamaruddin, W. H. A., Liu, C., Sun, C., & Wang, J. (2025) · BMEMat · doi:10.1002/bmm2.70044 · Cited by 8 · see citing works
Bai, Y., Zhu, Y., He, X., Huang, R., Xu, X., Yang, L., Wang, Z., & Zhu, R. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s463141 · Cited by 8 · see citing works
Graphene-Based Materials for Efficient Neurogenesis
Cho, Y., Lee, K., & Kim, T. P. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-981-16-4923-3_3 · Cited by 6 · see citing works
The enhanced generation of motor neurons from mESCs by MgAl layered double hydroxide nanoparticles
Bai, Y., Wang, Z., Yu, L., Dong, K., Cheng, L., & Zhu, R. (2023) · Biomedical Materials · doi:10.1088/1748-605x/acc375 · Cited by 6 · see citing works
Stem Cells Controlling, Imaging and Labeling by Functional Nanomaterials
Wei, Y., Zhou, L., Yang, D., Yao, T., & Shi, S. (2018) · Nano LIFE · doi:10.1142/s1793984418410076 · Cited by 3 · see citing works
Promoting the neural differentiation of embryonic stem cells by using thermosensitive nanocomposites
Cheng, S., Yu, F., Lu, B., Wang, H., & Yuan, L. (2021) · Materials Advances · doi:10.1039/d1ma00184a · Cited by 1 · see citing works
Engineered Biomaterials for Human Neural Stem Cell Applications
Ma, W. (2019) · TUScholarShare (Temple University)
Seong, J., Chun, C., Smith, A. S. T., Joo, J., & Mack, D. L. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.113275
DMF-ChIP-seq for Highly Sensitive and Integrated Epigenomic Profiling of Low-Input Cells
Li, M., Xing, N., Lin, F., Liang, S., Huang, Y., Song, J. T., Xu, X. J., & Yang, C. J. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c11280
Self-citationZhang, L., Wang, Y., Qiu, W., Liu, S., Xu, S., Wang, H., & Yuan, L. (2026) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2026.115554
- Authors
- Park, S.-J., Kim, S., Kim, S.-Y., Jeon, N. L., Song, J. M., Won, C., & Min, D.-H.
- Affiliations
- Center for RNA Research, Institute for Basic Science (IBS), Seoul National University, Seoul 08826, Republic of Korea
- Seoul National University (KR)
- Lemonex (South Korea) (KR)
- Corresponding author
- Min, Dal-Hee
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-09-27
- Volume
- 9
- Issue
- 40
- Pages
- 34634-34640
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2754547157
- Cited by
- 28
- References
- 19
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 2
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (2014K1B1A1073716, 2016R1A4A1010796, 2016R1E1A1A01941202)
- Institute for Basic Science (IBS-R008-D1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- neuronal differentiation, mouse embryonic stem cells, retinoic acid, mesoporous silica nanoparticles, nanoparticle drug delivery, neural induction, cell conversion
- MeSH terms
- Mouse Embryonic Stem Cells, Animals, Cell Differentiation, Tretinoin, Mice, Nanoparticles, Embryoid Bodies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
