The Effect of Wharton’s Jelly Mesenchymal Stem Cells on Nestin Gene Expression in Alzheimer's Rat Models

Annita Annita; Arniat Christiani Telaumbanua; Yanti Rahayu; Putri Dafriani; Hendri Panus

doi:10.30633/jsm.v9i1.30890

The Effect of Wharton’s Jelly Mesenchymal Stem Cells on Nestin Gene Expression in Alzheimer's Rat Models

Annita Annita, Arniat Christiani Telaumbanua, Yanti Rahayu, Putri Dafriani, Hendri Panus

Abstract

Alzheimer's disease (AD) is characterized by neurodegeneration and decreased neurogenesis due to neuroinflammation and free radical accumulation. Nestin is an intermediate filament protein that serves as a primary marker for neural progenitor cells in the neurogenesis process. This study aimed to analyze the effect of Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSCs) administration on Nestin gene expression in an Alzheimer's rat model. This experimental study with a posttest-only control group design utilized male white rats (Rattus norvegicus) induced by Aluminum chloride (AlCl³) at a dose of 300 mg/kg BW orally for 5 days to model Alzheimer's pathology. A dose of 1×10⁶ WJ-MSCs was injected intraperitoneally in the treatment group. One month post-therapy, Nestin gene expression from brain tissue was analyzed using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and statistically tested with One-Way ANOVA. The results showed a statistically significant difference (p < 0.05), with a significant increase in Nestin gene expression in the WJ-MSCs treated group compared to the positive control group. It is concluded that the administration of WJ-MSCs effectively increases Nestin gene expression, indicating an improvement in the regeneration and neurogenesis processes in the brain tissue of Alzheimer's rat models.

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Ababneh, N. A., AlDiqs, R., Nashwan, S., Ismail, M. A., Barham, R., Alatoom, R. M., Nairat, F., Gharandouq, M. H., Al-Qaisi, T., Awidi, A., & Saleh, T. (2025). Exosomes Derived from Induced and Wharton’s Jelly-Derived Mesenchymal Stem Cells Promote Senescence-like Features and Migration in Cancer Cells. International Journal of Molecular Sciences, 26(13), 1–18. https://doi.org/10.3390/ijms26136178

Abshenas, R., Artimani, T., Shahidi, S., Ranjbar, A., Komaki, A., Salehi, I., Amiri, I., & Soleimani Asl, S. (2020). Treadmill exercise enhances the promoting effects of preconditioned stem cells on memory and neurogenesis in Aβ-induced neurotoxicity in the rats. In Life Sciences (Vol. 249). https://doi.org/10.1016/j.lfs.2020.117482

Aghaei, Z., Karbalaei, N., Namavar, M. R., Haghani, M., Razmkhah, M., Ghaffari, M. K., & Nemati, M. (2023). Neuroprotective Effect of Wharton ’ s Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium ( WJMSC-CM ) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress , Neuroinflammation , and Apoptosis. Stem Cells International.

Annita, A., Revilla, G., Ali, H., & Almurdi, A. (2023). Exploring the Effects of Bone Marrow Mesenchymal Stem Cells on Amyloid Plaque Reduction in a Rat Model of Alzheimer ’ s Disease. 46(6), 1036–1044.

Annita, Revilla, G., Ali, H., & Almurdi. (2024). The Effect of Bone Marrow Mesenchymal Stem Cells on Nestin and Sox-2 Gene Expression and Spatial Learning (Percent Alternation Y-Maze Test) against AlCl3-Induced Alzheimer’s-like Pathology in a Rat Model. Iranian Journal of Medical Sciences, 49(7), 441–449. https://doi.org/10.30476/ijms.2023.98912.3104

Chiu, Y. S., Wu, K. J., Yu, S. J., Wu, K. L., Hsieh, C. Y., Chou, Y. S., Chen, K. Y., Wang, Y. S., Bae, E. K., Hung, T. W., Lin, S. H., Lin, C. H., Hsu, S. C., Wang, Y., & Chen, Y. H. (2024). Transplantation of Exosomes Derived From Human Wharton’s Jelly Mesenchymal Stromal Cells Enhances Functional Improvement in Stroke Rats. Cell Transplantation, 33(X). https://doi.org/10.1177/09636897241296366

Chun, S. Y., Lim, J. O., Lee, E. H., Han, M. H., Ha, Y. S., Lee, J. N., Kim, B. S., Park, M. J., Yeo, M. G., Jung, B., & Kwon, T. G. (2019). Preparation and Characterization of Human Adipose Tissue-Derived Extracellular Matrix, Growth Factors, and Stem Cells: A Concise Review. Tissue Engineering and Regenerative Medicine, 16(4), 385–393. https://doi.org/10.1007/s13770-019-00199-7

Endrinaldi, E., Darwin, E., Zubir, N., & Revilla, G. (2019). The effect of mesenchymal stem cell wharton’s jelly on matrix metalloproteinase-1 and interleukin-4 levels in osteoarthritis rat model. Open Access Macedonian Journal of Medical Sciences, 7(4), 529–535. https://doi.org/10.3889/OAMJMS.2019.152

Farrokhfar, S., Tiraihi, T., Movahedin, M., & Azizi, H. (2020). Differential gene expression by lithium chloride induction of adipose-derived stem cells into neural phenotype cells. Iranian Journal of Basic Medical Sciences, 23(4), 544–550. https://doi.org/10.22038/ijbms.2020.41582.9820

Frost, G. R., Jonas, L. A., & Li, Y. M. (2019). Friend, Foe or Both? Immune Activity in Alzheimer’s Disease. Frontiers in Aging Neuroscience, 11(December), 1–20. https://doi.org/10.3389/fnagi.2019.00337

Goyal, U., Jaiswal, C., & TA, M. (2018). Isolation and Establishment of Mesenchymal Stem Cells from Wharton’s Jelly of Human Umbilical Cord. Bio-Protocol, 8(4), 1–13. https://doi.org/10.21769/bioprotoc.2735

Hayashi, Y., Lin, H. T., Lee, C. C., & Tsai, K. J. (2020). Effects of neural stem cell transplantation in Alzheimer’s disease models. Journal of Biomedical Science, 27(1), 1–11. https://doi.org/10.1186/s12929-020-0622-x

Hernández, R., Jiménez-Luna, C., Perales-Adán, J., Perazzoli, G., Melguizo, C., & Prados, J. (2020). Differentiation of human mesenchymal stem cells towards neuronal lineage: Clinical trials in nervous system disorders. Biomolecules and Therapeutics, 28(1), 34–44. https://doi.org/10.4062/biomolther.2019.065

Kruminis-Kaszkiel, E., Osowski, A., Bejer-Oleńska, E., Dziekoński, M., & Wojtkiewicz, J. (2020). Differentiation of Human Mesenchymal Stem Cells from Wharton’s Jelly Towards Neural Stem Cells Using a Feasible and Repeatable Protocol. Cells, 9(3), 739. https://doi.org/10.3390/cells9030739

Liu, X. Y., Yang, L. P., & Zhao, L. (2020). Stem cell therapy for alzheimer’s disease. World Journal of Stem Cells, 12(8), 787–802. https://doi.org/10.4252/WJSC.V12.I8.787

Luo, R., Zhang, J., Chen, P., Wang, L., Wang, W., Wang, P., Zhao, X., & Tian, W. (2025). Curcumin-Loaded Mesenchymal Stem Cell-Derived Exosomes: A Potential Effective Strategy for NAFLD. Journal of Food Biochemistry, 2025(1). https://doi.org/10.1155/jfbc/6134296

Meyer, K., Feldman, H. M., Lu, T., Drake, D., Lim, E. T., Ling, K. H., Bishop, N. A., Pan, Y., Seo, J., Lin, Y. T., Su, S. C., Church, G. M., Tsai, L. H., & Yankner, B. A. (2019). REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer’s Disease. Cell Reports, 26(5), 1112-1127.e9. https://doi.org/10.1016/j.celrep.2019.01.023

Potokar, M., Morita, M., Wiche, G., & Jorgačevski, J. (2020). The Diversity of Intermediate Filaments in Astrocytes. Cells, 9(7). https://doi.org/10.3390/cells9071604

Qin, C., Li, Y., & Wang, K. (2021). Functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with alzheimer’s disease: Inhibition of neuroinflammation. Journal of Inflammation Research, 14(August), 4761–4775. https://doi.org/10.2147/JIR.S327538

Qin, C., Wang, K., Zhang, L., & Bai, L. (2022). Stem cell therapy for Alzheimer’s disease: An overview of experimental models and reality. Animal Models and Experimental Medicine, 5(1), 15–26. https://doi.org/10.1002/ame2.12207

Rinendyaputri, R., Nainggolan, I. M., Idrus, H. H., Noverina, R., Ayuningtyas, W., Huda, F., & Faried, A. (2025). In vitro and In vivo Studies on Mesenchymal Stem Cells for Ischemic Stroke Therapy: A Scoping Review of The Therapeutic Effect. Stem Cells and Cloning: Advances and Applications, 18(May), 45–61. https://doi.org/10.2147/SCCAA.S519338

Si, Y., Dong, S., Li, M., Gu, J., Luo, M., Wang, X., Wang, Z., Li, X., & Zhang, C. (2025). Curcumin-encapsulated exosomes in bisphosphonate-modified hydrogel microspheres promote bone repair through macrophage polarization and DNA damage mitigation. Materials Today Bio, 32(March), 101874. https://doi.org/10.1016/j.mtbio.2025.101874

Thomi, G., Surbek, D., Haesler, V., Joerger-Messerli, M., & Schoeberlein, A. (2019). Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Research and Therapy, 10(1), 1–16. https://doi.org/10.1186/s13287-019-1207-z

Wei, Y., Xie, Z., Bi, J., & Zhu, Z. (2018). Anti-inflammatory effects of bone marrow mesenchymal stem cells on mice with alzheimer’s disease. Experimental and Therapeutic Medicine, 16(6), 5015–5020. https://doi.org/10.3892/etm.2018.6857

Wulandari, L. Y. (2019). Ulasan Pustaka : Sel Punca Adiposa Sebagai Alternatif. Jurnal Farmasi Malahayati, 2(2), 175–185.

Xiaopeng, Z., Jing, Y., Xia, L., Xingsheng, W., & Juan, D. (2025). Global Burden of Alzheimer ’ s disease and other dementias in adults aged years and older ,. Frontiers in Public Helath, 13(1585711).

Yang, H., Xie, Z. H., Wei, L. F., Yang, H. N., Yang, S. N., Zhu, Z. Y., Wang, P., Zhao, C. P., & Bi, J. Z. (2013). Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model. In Stem Cell Research and Therapy (Vol. 4, Issue 4). https://doi.org/10.1186/scrt227

Zhang, L., Xu, M., Ren, Q., Liu, G., Meng, S., Xiahou, K., Zhang, Y., Jiang, N., & Zhou, W. (2020). Human Induced Pluripotent Stem Cell-Derived Neural Cells from Alzheimer’s Disease Patients Exhibited Different Susceptibility to Oxidative Stress. Stem Cells and Development, 29(22), 1444–1456. https://doi.org/10.1089/scd.2020.0103

Zhao, Y., Dang, M., Zhang, W., Lei, Y., Ramesh, T., Priya Veeraraghavan, V., & Hou, X. (2020a). Neuroprotective effects of Syringic acid against aluminium chloride induced oxidative stress mediated neuroinflammation in rat model of Alzheimer’s disease. Journal of Functional Foods, 71(April), 104009. https://doi.org/10.1016/j.jff.2020.104009

Zhao, Y., Dang, M., Zhang, W., Lei, Y., Ramesh, T., Priya Veeraraghavan, V., & Hou, X. (2020b). Neuroprotective effects of Syringic acid against aluminium chloride induced oxidative stress mediated neuroinflammation in rat model of Alzheimer’s disease. Journal of Functional Foods, 71(February), 104009. https://doi.org/10.1016/j.jff.2020.104009

DOI: http://dx.doi.org/10.30633/jsm.v9i1.30890