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Article: Small molecules efficiently reprogram apical papilla stem cells into neuron‑like cells

TitleSmall molecules efficiently reprogram apical papilla stem cells into neuron‑like cells
Authors
Keywordssmall molecule
stem cells
apical papilla
differentiation
neurogenesis
Issue Date2021
PublisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com
Citation
Experimental and Therapeutic Medicine, 2021, v. 21 n. 6, p. article no. 546 How to Cite?
AbstractStem cell‑based therapy may provide a novel approach for neural tissue regeneration. A small molecule cocktail‑based culture protocol was previously shown to enhance neurogenic differentiation of stem cells from dental tissues. The present study aimed to investigate the early phase of small molecule‑induced neurogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were cultured in neural‑induction medium or neural‑induction medium with small molecules (NIMS‑SCAP) and examined for their cell morphologies. Expression levels of neural progenitor cell‑related markers, including Nestin, paired‑box gene 6 (Pax6) and Sry‑related HMG box 2 (Sox2), were examined using western blotting and immunocytofluorescence. Expression of differentiated neuron‑related markers, including neurofilament protein (NFM), neuron‑specific nuclear protein (NeuN) and microtubule‑associated protein (MAP)‑2, were also examined using western blotting, while NFM and MAP2 gene expression and cell proliferation were assessed using reverse transcription‑quantitative (RT‑q)PCR and Cell Counting Kit (CCK)‑8 assays, respectively. SCAP morphology was affected by small molecules after as little as 30 min. Specifically, Nestin, Pax6 and Sox2 expression detected using western blotting was increased by day 3 but then decreased over the course of 7 days with neural induction, while immunocytofluorescence revealed expression of all three markers in NIMS‑SCAP. The protein levels of NFM, NeuN and MAP2 on day 7 were significantly upregulated in NIMS‑SCAP, as detected using western blotting, while NFM and MAP2 gene expression levels detected using RT‑qPCR were significantly increased on days 5 and 7. Proliferation of NIMS‑SCAP ceased after 5 days. Electrophysiological analysis showed that only SCAP cultured in NIMS had the functional activity of neuronal cells. Thus, small molecules reprogrammed SCAP into neural progenitor cells within the first 3 days, followed by further differentiation into neuron‑like cells.
Persistent Identifierhttp://hdl.handle.net/10722/300551
ISSN
2023 Impact Factor: 2.4
2019 SCImago Journal Rankings: 0.508
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, Q-
dc.contributor.authorYuan, C-
dc.contributor.authorJiang, S-
dc.contributor.authorHeng, BC-
dc.contributor.authorZou, T-
dc.contributor.authorShen, Z-
dc.contributor.authorWang, P-
dc.contributor.authorZhang, C-
dc.date.accessioned2021-06-18T14:53:36Z-
dc.date.available2021-06-18T14:53:36Z-
dc.date.issued2021-
dc.identifier.citationExperimental and Therapeutic Medicine, 2021, v. 21 n. 6, p. article no. 546-
dc.identifier.issn1792-0981-
dc.identifier.urihttp://hdl.handle.net/10722/300551-
dc.description.abstractStem cell‑based therapy may provide a novel approach for neural tissue regeneration. A small molecule cocktail‑based culture protocol was previously shown to enhance neurogenic differentiation of stem cells from dental tissues. The present study aimed to investigate the early phase of small molecule‑induced neurogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were cultured in neural‑induction medium or neural‑induction medium with small molecules (NIMS‑SCAP) and examined for their cell morphologies. Expression levels of neural progenitor cell‑related markers, including Nestin, paired‑box gene 6 (Pax6) and Sry‑related HMG box 2 (Sox2), were examined using western blotting and immunocytofluorescence. Expression of differentiated neuron‑related markers, including neurofilament protein (NFM), neuron‑specific nuclear protein (NeuN) and microtubule‑associated protein (MAP)‑2, were also examined using western blotting, while NFM and MAP2 gene expression and cell proliferation were assessed using reverse transcription‑quantitative (RT‑q)PCR and Cell Counting Kit (CCK)‑8 assays, respectively. SCAP morphology was affected by small molecules after as little as 30 min. Specifically, Nestin, Pax6 and Sox2 expression detected using western blotting was increased by day 3 but then decreased over the course of 7 days with neural induction, while immunocytofluorescence revealed expression of all three markers in NIMS‑SCAP. The protein levels of NFM, NeuN and MAP2 on day 7 were significantly upregulated in NIMS‑SCAP, as detected using western blotting, while NFM and MAP2 gene expression levels detected using RT‑qPCR were significantly increased on days 5 and 7. Proliferation of NIMS‑SCAP ceased after 5 days. Electrophysiological analysis showed that only SCAP cultured in NIMS had the functional activity of neuronal cells. Thus, small molecules reprogrammed SCAP into neural progenitor cells within the first 3 days, followed by further differentiation into neuron‑like cells.-
dc.languageeng-
dc.publisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com-
dc.relation.ispartofExperimental and Therapeutic Medicine-
dc.subjectsmall molecule-
dc.subjectstem cells-
dc.subjectapical papilla-
dc.subjectdifferentiation-
dc.subjectneurogenesis-
dc.titleSmall molecules efficiently reprogram apical papilla stem cells into neuron‑like cells-
dc.typeArticle-
dc.identifier.emailZou, T: zouting6@hku.hk-
dc.identifier.emailZhang, C: zhangcf@hku.hk-
dc.identifier.authorityZhang, C=rp01408-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3892/etm.2021.9978-
dc.identifier.pmid33850518-
dc.identifier.pmcidPMC8027758-
dc.identifier.hkuros322784-
dc.identifier.volume21-
dc.identifier.issue6-
dc.identifier.spagearticle no. 546-
dc.identifier.epagearticle no. 546-
dc.identifier.isiWOS:000638209800001-
dc.publisher.placeGreece-

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