Adipose stem cells preincubated with theanine exert liver regeneration through increase of stem cell paracrine VEGF and suppression of ROS, pyroptosis as well as autophagy markers in liver damage induced by N-nitrosodiethylamine
Abstract
Aims Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell protection. This study investigates if protective effect on the liver by stem cells preincubated with theanine is better than that from stem cells without preincubated theanine. Methods We transplanted theanine preincubated adipose-derived stem cells (ADSC) to male Wistar rats with liver dysfunction induced by N-nitrosodiethylamine. The viability, migration and antioxidant capabilities were performed in the ADSC pre-incubated with theanine. Hepatic functional, structural and molecular assays were determined in the animals with or without theanine preincubated ADSC. Key findings Cell model revealed that ADSC preincubated with green tea theanine (T-ADSC) increased cell capabilities including viability, migration and paracrine secretion. In vivo results indicated that several pathological conditions were observed in rats with liver injury induced by DEN including structural changes and expression of pyroptosis as well as autophagy markers. The above pathological conditions were improved when the rats received both ADSC and T-ADSC treatment. Furthermore, T-ADSC showed better therapeutic effect on rats with liver injury than ADSC due to significant suppression of pyroptosis markers caspase-1 and IL-1β as well as autophagy marker LC3-II accompanied with intensive paracrine VEGF from T-ADSC. Significance Increased paracrine VEGF secretion from T-ADSC plays a crucial role in liver regeneration. A future clinical study may be designed for further verification of these experimental in vivo findings.
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?
Pretreatment with melatonin or bioactive compounds such as theanine and glycyrrhizic acid enhances the homing, hepatocyte-like differentiation, and paracrine function of MSCs.
“Moreover, pretreatment with melatonin or bioactive compounds, such as theanine and glycyrrhizic acid, has been shown to enhance the homing, hepatocyte-like differentiation, and paracrine function of MSCs [352–354].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [354]
Cites
Burden of liver diseases in the world
Asrani, S. K., Devarbhavi, H., Eaton, J., & Kamath, P. S. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.09.014 · Cited by 3,783 · see citing works
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K. S., Powell-Braxton, L., Hillan, K. J., & Moore, M. W. (1996) · Nature · doi:10.1038/380439a0 · Cited by 3,624 · see citing works
Oxidative stress as a crucial factor in liver diseases
Cichoż‐Lach, H. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i25.8082 · Cited by 1,226 · see citing works
Adipose-derived stem cells: Isolation, expansion and differentiation☆
Bunnell, B. A., Flaat, M., Gagliardi, C., PATEL, B., & RIPOLL, C. (2008) · Methods · doi:10.1016/j.ymeth.2008.03.006 · Cited by 1,069 · see citing works
Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes.
Frank, S., Hübner, G., Breier, G., Longaker, M. T., Greenhalgh, D. G., & Werner, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.21.12607 · Cited by 764 · see citing works
Autophagy in the liver: functions in health and disease
Ueno, T., & Komatsu, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.185 · Cited by 500 · see citing works
Platelet: transporter of vascular endothelial growth factor.
Verheul, H. M. W., Hoekman, K., Bakker, S., Eekman, C., Folman, C. C., Broxterman, H. J., & Pinedo, H. M. (1997) · PubMed · Cited by 378 · see citing works
Yin, X., Ding, W., & Gao, W. (2008) · Hepatology · doi:10.1002/hep.22146 · Cited by 254 · see citing works
Pyroptosis in Liver Disease: New Insights into Disease Mechanisms
Wu, J., Lin, S., Wan, B., Velani, B., & Zhu, Y. (2019) · Aging and Disease · doi:10.14336/ad.2019.0116 · Cited by 155 · see citing works
Biological and medical physics, biomedical engineering
Herman, I. P. (2014) · Cited by 136 · see citing works
Chintalgattu, V. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00006-3 · Cited by 128 · see citing works
Liao, N., Shi, Y., Zhang, C., Zheng, Y., Wang, Y., Zhao, B., Zeng, Y., Liu, X., & Liu, J. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1404-9 · Cited by 127 · see citing works
Lin, M., Liu, X., Zheng, H., Huang, X., Wu, Y., Huang, A., Zhu, H., Hu, Y., Mai, W., & Huang, Y. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1544-y · Cited by 111 · see citing works
Kai, J., Xiang, Y., Wang, Z., Wang, F., Jia, Y., Wang, S., Tan, S., Chen, A., Shao, J., Zhang, F., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.03.031 · Cited by 101 · see citing works
Role of pyroptosis in liver diseases
Mamun, A. A., Wu, Y., Jia, C., Munir, F., Sathy, K. J., Sarker, T., Monalisa, I., Zhou, K., & Xiao, J. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106489 · Cited by 89 · see citing works
Long-Term Results of Liver Transplantation
Åberg, F. O., Isoniemi, H., & Höckerstedt, K. (2011) · Scandinavian Journal of Surgery · doi:10.1177/145749691110000104 · Cited by 88 · see citing works
Lai, C., Ho, T., Kuo, W., Day, C. H., Pai, P., Chung, L.-C., Liao, P., Lin, F., Wu, E.-T., & Huang, C. (2014) · AGE · doi:10.1007/s11357-014-9706-4 · Cited by 77 · see citing works
Chen, Z., Wang, Z., Yuan, H., & He, N. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c06694 · Cited by 67 · see citing works
Zhao, H., Huang, H., Alam, A., Chen, Q., Suen, K. C., Jiang, C., Sun, Q., Ologunde, R., Zhang, W., Lian, Q., et al. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14699 · Cited by 66 · see citing works
Yuan, L., Liu, J., Deng, H. X., & Gao, C. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b03248 · Cited by 63 · see citing works
Kishida, N., Matsuda, S., Itano, O., Shinoda, M., Kitago, M., Yagi, H., Abe, Y., Hibi, T., Masugi, Y., Aiura, K., et al. (2016) · BMC Gastroenterology · doi:10.1186/s12876-016-0477-5 · Cited by 54 · see citing works
Dirscherl, K., Schläpfer, M., Z’graggen, B. R., Wenger, R. H., Booy, C., Flury-Frei, R., Fatzer, R., Aloman, C., Bartosch, B., Parent, R., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-60709-9 · Cited by 49 · see citing works
Liao, P., Hsieh, D. J., Kuo, C., Day, C. H., Shen, C.-Y., Lai, C., Chen, R., Padma, V. V., Kuo, W., & Huang, C. (2015) · Oncotarget · doi:10.18632/oncotarget.6168 · Cited by 40 · see citing works
Bai, H., Zhang, Z.-H., Li, Y., Song, X.-P., Ma, T.-W., Liu, C.-P., Liu, L., Yuan, R., Wang, X., & Gao, L. (2020) · Nutrients · doi:10.3390/nu12071988 · Cited by 39 · see citing works
Li, H., Yuan, L., Li, X., Luo, Y., Zhang, Z., & Li, J. (2021) · Antioxidants · doi:10.3390/antiox10081275 · Cited by 33 · see citing works
Li, C., Yan, Q., Tang, S., Xiao, W., & Tan, Z. (2018) · Medical Science Monitor · doi:10.12659/msm.907660 · Cited by 32 · see citing works
LIU, T., Mu, H., Shen, Z., Song, Z., Chen, X., & Wang, Y. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4768 · Cited by 27 · see citing works
Chen, T., Ju, D., Day, C. H., Yeh, Y., Chen, R., Viswanadha, V. P., Chang, R., Lin, Y., Yao, C., & Huang, C. (2019) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2917 · Cited by 20 · see citing works
Self-citationKambakamba, P., Linecker, M., Schneider, M. A., Kron, P., Limani, P., Tschuor, C., Ungethüm, U., Humar, B., & Clavien, P. (2018) · Annals of Surgery · doi:10.1097/sla.0000000000002891 · Cited by 16 · see citing works
Chen, Y., Lian, F., Lu, Q., Peng, S., Li, J., Huang, S. M., & Du, X. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00790 · Cited by 15 · see citing works
Yuan, K., Lai, C., Wei, L., Feng, T., Yang, Q., Zhang, T., Lan, T., Yao, Y., Xiang, G., & Huang, X. (2019) · Stem Cells International · doi:10.1155/2019/5310202 · Cited by 14 · see citing works
Chang, X., Yang, Q., Zhang, C., Zhang, Y. W., Liang, X., Liu, Y., & Xu, G. (2019) · Cell Biochemistry and Function · doi:10.1002/cbf.3402 · Cited by 13 · see citing works
Chen, L., Wen-jun, X., Yan, Q., Gong, Z., Zhang, S., Zeng, L., Yang, M. H., & Zhou, Y. (2020) · Archives of Pharmacal Research · doi:10.1007/s12272-020-01248-9 · Cited by 10 · see citing works
Metabolic liver disease — what’s in a name?
Herman, M. A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00452-3 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Huai, Q., Zhu, C., Zhang, X., Dai, H., Li, X., & Wang, H. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01122-3 · Cited by 27 · see citing works
Janmeda, P., Jain, D., Chaudhary, P., Meena, M., & Singh, D. (2024) · Journal of Applied Toxicology · doi:10.1002/jat.4574 · Cited by 20 · see citing works
Elbaz, E. M., Ibrahim, S. M., Rashad, E., Yasin, N. A. E., Ghaiad, H. R., & Mehana, N. A. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00351 · Cited by 21 · see citing works
Wang, Z., Yao, L., Hu, X., Yuan, M., Chen, P., Liu, P., Zhang, Q., Xiong, Z., Dai, K., & Jiang, Y. (2023) · Tissue and Cell · doi:10.1016/j.tice.2023.102198 · Cited by 9 · see citing works
Natural products for migraine: Data-mining analyses of Chinese Medicine classical literature
Zhang, C. S., Lyu, S., Zhang, A. L., Guo, X., Sun, J., Lu, C., Luo, X., & Xue, C. C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.995559 · Cited by 7 · see citing works
Tea and Blood–Brain Barrier Homeostasis: Potential Mechanisms and Improvement Strategies
Yue, R., Wen, H., He, L., Liu, Y., Zeng, L., & Luo, L. (2025) · Food Frontiers · doi:10.1002/fft2.70125 · Cited by 6 · see citing works
Huang, C.-M., Cheng, Y., Yi-Hua, L., & Chien, C. (2026) · Life Sciences · doi:10.1016/j.lfs.2026.124364 · Cited by 3 · see citing works
Self-citationPan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2 · see citing works
Yi, W., Li, L., Wang, Y., Chen, Y., Li, Z., Huang, C., Wei, Y., Jia, C., Zuo, W., & Liao, J. (2024) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2024.5370 · Cited by 2 · see citing works
Theanine (l-glutamylethylamide) in tea and its protective effects against bladder dysfunction
Matsuoka, K., Akaihata, H., Hata, J., Tanji, R., Ogawa, S., & Kojima, Y. (2024) · Tea in Health and Disease Prevention · doi:10.1016/b978-0-443-14158-4.00050-6
Wang, Z., Li, M., Yan, X., Liu, Y., Yang, P., Liu, W., & Guan, W. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262411798
Ban, Q., Chi, W., Wang, Q., Li, J., Xia, Y., Meng, Y., Li, M., Zhao, R., Yu, Y., Kan, Z., et al. (2026) · Nutrients · doi:10.3390/nu18183098
- Authors
- Chen, T.-S., Lai, Y.-A., Lai, Y.-J., & Chien, C.-T.
- Affiliations
- National Taiwan Normal University (TW)
- Corresponding author
- Lai, Yun-Ju
- Chien, Chiang-Ting
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 308
- Pages
- 120969
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W4296269967
- Cited by
- 12
- References
- 35
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology, Taiwan (106-2320-B-003-002-MY3)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- adipose-derived stem cells, theanine, liver regeneration, diethylnitrosamine, liver injury, pyroptosis, autophagy, reactive oxygen species, vascular endothelial growth factor, paracrine signaling, caspase-1, IL-1β, green tea, stem cell therapy
- MeSH terms
- Pyroptosis, Adipose Tissue, Animals, Antioxidants, Autophagy, Diethylnitrosamine, Glutamates, Liver Diseases, Liver Regeneration, Male, Quality of Life, Stem Cells, Tea, Biomarkers, Rats, Wistar, Reactive Oxygen Species, Caspases, Vascular Endothelial Growth Factor A, Rats
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