Vol. 11 No. 8 (2025): August
Open Access
Peer Reviewed

Encapsulated Mesenchymal Stem Cell as Regenerative Alternative for MDR-TB: A Gene Expression Analysis of ABCG2 Efflux

Authors

Christine Verawaty Sibuea , Dina Octafrida Marpaung , Ervina Julien Sitanggang , Ade Pryta Simaremare , Cindy Destasya Masal , George Azriel Buala Nama Laia , Octora Angelica Violyn Tambunan , Wanda Lucia Samosir , Cici Kres Sidabalok

DOI:

10.29303/jppipa.v11i8.12040

Published:

2025-08-25

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Abstract

Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health challenge due to poor treatment outcomes. Encapsulated mesenchymal stem cells (MSCs) have emerged as a potential alternative therapy; however, their role in modulating bacterial drug sensitivity remains unclear. This study aimed to evaluate the expression of the ABCG2 efflux pump gene in encapsulated MSCs co-cultured with MDR-TB, and to explore its implications for bacterial sensitivity to anti-tuberculosis drugs. An in vitro experimental design was employed using encapsulated MSCs cultured with MDR-TB. Total RNA was isolated, converted into complementary DNA (cDNA), and analyzed using quantitative real-time PCR (RT-PCR). Gene expression levels were quantified using the Livak (ΔΔCt) method. Results demonstrated a progressive increase in ABCG2 gene expression on days 2, 7, and 14. Although this increase may reduce the direct antibacterial capacity of MSCs, previous studies have shown that their preserved paracrine function remains beneficial for immunomodulation. These findings support the continued investigation of encapsulated MSCs as an adjunctive therapy for MDR-TB, particularly through immunoregulatory mechanisms despite increased ABCG2 expression.

Keywords:

ABCG2 Encapsulated MDR-TB MSCs

References

Battah, B. (2022). Mesenchymal Stem Cells: Potential Role against Bacterial Infection. Journal of Biosciences and Medicines, 10(03), 97–113. https://doi.org/10.4236/jbm.2022.103011

Bogiel, T., Dolska, E., Zimna, M., Nakonowska, K., Krawiecka, D., Żebracka, R., Pochowski, M., & Krawczyk, A. (2025). The Usefulness of the BD MAX MDR-TB Molecular Test in the Rapid Diagnosis of Multidrug-Resistant Tuberculosis. Pathogens, 14(6), 602. https://doi.org/10.3390/pathogens14060602

Bolinas, D. K. M., Barcena, A. J. R., Mishra, A., Bernardino, M. R., Lin, V., Heralde, F. M., Chintalapani, G., Fowlkes, N. W., Huang, S. Y., & Melancon, M. P. (2025). Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats. Gels, 11(4), 250. https://doi.org/10.3390/gels11040250

Chandran, C., Santra, M., Rubin, E., Geary, M. L., & Yam, G. H.-F. (2024). Regenerative Therapy for Corneal Scarring Disorders. Biomedicines, 12(3), 649. https://doi.org/10.3390/biomedicines12030649

Chen, Y.-S., Jin, E., & Day, P. J. (2024). Use of Drug Sensitisers to Improve Therapeutic Index in Cancer. Pharmaceutics, 16(7), 928. https://doi.org/10.3390/pharmaceutics16070928

Cortes-Dericks, L., & Galetta, D. (2025). An Overview of Cellular and Molecular Determinants Regulating Chemoresistance in Pleural Mesothelioma. Cancers, 17(6), 979. https://doi.org/10.3390/cancers17060979

Devi, A., Pahuja, I., Singh, S. P., Verma, A., Bhattacharya, D., Bhaskar, A., Dwivedi, V. P., & Das, G. (2023). Revisiting the role of mesenchymal stem cells in tuberculosis and other infectious diseases. Cellular & Molecular Immunology, 20(6), 600–612. https://doi.org/10.1038/s41423-023-01028-7

Fanelli, G., Pasqua, M., Colonna, B., Prosseda, G., & Grossi, M. (2020). Expression Profile of Multidrug Resistance Efflux Pumps During Intracellular Life of Adherent-Invasive Escherichia coli Strain LF82. Frontiers in Microbiology, 11, 1935. https://doi.org/10.3389/fmicb.2020.01935

Frąszczak, K., & Barczyński, B. (2023). The Role of Cancer Stem Cell Markers in Ovarian Cancer. Cancers, 16(1), 40. https://doi.org/10.3390/cancers16010040

Guan, A., Alibrandi, L., Verma, E., Sareen, N., Guan, Q., Lionetti, V., & Dhingra, S. (2025). Clinical translation of mesenchymal stem cells in ischemic heart failure: Challenges and future perspectives. Vascular Pharmacology, 159, 107491. https://doi.org/10.1016/j.vph.2025.107491

Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022). The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduction and Targeted Therapy, 7(1), 92. https://doi.org/10.1038/s41392-022-00932-0

Huang, Y., Li, X., & Yang, L. (2022). Hydrogel Encapsulation: Taking the Therapy of Mesenchymal Stem Cells and Their Derived Secretome to the Next Level. Frontiers in Bioengineering and Biotechnology, 10, 859927. https://doi.org/10.3389/fbioe.2022.859927

Jain, N., Kalam, H., Singh, L., Sharma, V., Kedia, S., Das, P., Ahuja, V., & Kumar, D. (2020). Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis. Nature Communications, 11(1), 3062. https://doi.org/10.1038/s41467-020-16877-3

Kumar, S., Kabat, M., Basak, S., Babiarz, J., Berthiaume, F., & Grumet, M. (2022). Anti-Inflammatory Effects of Encapsulated Human Mesenchymal Stromal/Stem Cells and a Method to Scale-Up Cell Encapsulation. Biomolecules, 12(12), 1803. https://doi.org/10.3390/biom12121803

Kuncorojakti, S., Rodprasert, W., Yodmuang, S., Osathanon, T., Pavasant, P., Srisuwatanasagul, S., & Sawangmake, C. (2020). Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells. Journal of Biological Engineering, 14(1), 23. https://doi.org/10.1186/s13036-020-00246-1

Lee, H., Kim, B., Park, J., Park, S., Yoo, G., Yum, S., Kang, W., Lee, J.-M., Youn, H., & Youn, B. (2025). Cancer stem cells: Landscape, challenges and emerging therapeutic innovations. Signal Transduction and Targeted Therapy, 10(1), 248. https://doi.org/10.1038/s41392-025-02360-2

Lee, J.-H., Shin, S.-J., Lee, J. H., Knowles, J. C., Lee, H.-H., & Kim, H.-W. (2024). Adaptive immunity of materials: Implications for tissue healing and regeneration. Bioactive Materials, 41, 499–522. https://doi.org/10.1016/j.bioactmat.2024.07.027

Li, Y., Dong, Y., Ran, Y., Zhang, Y., Wu, B., Xie, J., Cao, Y., Mo, M., Li, S., Deng, H., Hao, W., Yu, S., & Wu, Y. (2021). Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia. Stem Cell Research & Therapy, 12(1), 358. https://doi.org/10.1186/s13287-021-02416-4

Ma, M., Lustig, M., Salem, M., Mengin-Lecreulx, D., Phan, G., & Broutin, I. (2021). MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa. International Journal of Molecular Sciences, 22(10), 5328. https://doi.org/10.3390/ijms22105328

Musiał-Wysocka, A., Kot, M., & Majka, M. (2019). The Pros and Cons of Mesenchymal Stem Cell-Based Therapies. Cell Transplantation, 28(7), 801–812. https://doi.org/10.1177/0963689719837897

Nair, A., Greeny, A., Nandan, A., Sah, R. K., Jose, A., Dyawanapelly, S., Junnuthula, V., K. V., A., & Sadanandan, P. (2023). Advanced drug delivery and therapeutic strategies for tuberculosis treatment. Journal of Nanobiotechnology, 21(1), 414. https://doi.org/10.1186/s12951-023-02156-y

Omoteso, O. A., Fadaka, A. O., Walker, R. B., & Khamanga, S. M. (2025). Innovative Strategies for Combating Multidrug-Resistant Tuberculosis: Advances in Drug Delivery Systems and Treatment. Microorganisms, 13(4), 722. https://doi.org/10.3390/microorganisms13040722

Rao, M., Ippolito, G., Mfinanga, S., Ntoumi, F., Yeboah-Manu, D., Vilaplana, C., Zumla, A., & Maeurer, M. (2019). Improving treatment outcomes for MDR-TB — Novel host-directed therapies and personalised medicine of the future. International Journal of Infectious Diseases, 80, S62–S67. https://doi.org/10.1016/j.ijid.2019.01.039

Ryoo, I., Lee, S., & Kwak, M.-K. (2016). Redox Modulating NRF2: A Potential Mediator of Cancer Stem Cell Resistance. Oxidative Medicine and Cellular Longevity, 2016(1), 2428153. https://doi.org/10.1155/2016/2428153

Sarhadi, V. K., Daddali, R., & Seppänen-Kaijansinkko, R. (2021). Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy. International Journal of Molecular Sciences, 22(20), 11035. https://doi.org/10.3390/ijms222011035

Sibuea, C. V., Pawitan, J., Antarianto, R., Jasirwan, C. O. M., Sianipar, I. R., Luviah, E., Nurhayati, R. W., Mubarok, W., & Mazfufah, N. F. (2020). 3D Co-Culture of Hepatocyte, a Hepatic Stellate Cell Line, and Stem Cells for Developing a Bioartificial Liver Prototype. International Journal of Technology, 11(5), 951. https://doi.org/10.14716/ijtech.v11i5.4317

Singh, V. K., Mishra, A., Bark, S., Mani, A., Subbian, S., Hunter, R. L., Jagannath, C., & Khan, A. (2020). Human mesenchymal stem cell based intracellular dormancy model of Mycobacterium tuberculosis. Microbes and Infection, 22(9), 423–431. https://doi.org/10.1016/j.micinf.2020.05.015

Soedarsono, S., Mertaniasih, N. M., Kusmiati, T., Permatasari, A., Ilahi, W. K., & Anggraeni, A. T. (2023). Characteristics of Previous Tuberculosis Treatment History in Patients with Treatment Failure and the Impact on Acquired Drug-Resistant Tuberculosis. Antibiotics, 12(3), 598. https://doi.org/10.3390/antibiotics12030598

Soeroto, A. Y., Pratiwi, C., Santoso, P., & Lestari, B. W. (2021). Factors affecting outcome of longer regimen multidrug-resistant tuberculosis treatment in West Java Indonesia: A retrospective cohort study. PLOS ONE, 16(2), e0246284. https://doi.org/10.1371/journal.pone.0246284

Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025). Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? Journal of Advanced Research, 70, 103–124. https://doi.org/10.1016/j.jare.2024.05.004

Uzuner, D., Akkoç, Y., Peker, N., Pir, P., Gözüaçık, D., & Çakır, T. (2021). Transcriptional landscape of cellular networks reveal interactions driving the dormancy mechanisms in cancer. Scientific Reports, 11(1), 15806. https://doi.org/10.1038/s41598-021-94005-x

Vohra, M., & Arora, S. K. (2023). Mesenchymal stem cells—The master immunomodulators. Exploration of Immunology, 104–122. https://doi.org/10.37349/ei.2023.00092

Wang, Y., Wang, L., Wei, Y., Wei, C., Yang, H., Chen, Q., Zhang, R., & Shen, H. (2024). Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy. Discover Oncology, 15(1), 184. https://doi.org/10.1007/s12672-024-01049-2

Wu, S., Zhou, Z., Li, Y., & Jiang, J. (2024). Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes. Heliyon, 10(17), e37031. https://doi.org/10.1016/j.heliyon.2024.e37031

Yang, L., Shi, F., Cao, F., Wang, L., She, J., He, B., Xu, X., Kong, L., & Cai, B. (2025). Neutrophils in Tissue Injury and Repair: Molecular Mechanisms and Therapeutic Targets. MedComm, 6(5), e70184. https://doi.org/10.1002/mco2.70184

Yang, S., Seo, J., Choi, J., Kim, S.-H., Kuk, Y., Park, K. C., Kang, M., Byun, S., & Joo, J.-Y. (2025). Towards understanding cancer dormancy over strategic hitching up mechanisms to technologies. Molecular Cancer, 24(1), 47. https://doi.org/10.1186/s12943-025-02250-9

Yudintceva, N., Bobkov, D., Sulatsky, M., Mikhailova, N., Oganesyan, E., Vinogradova, T., Muraviov, A., Remezova, A., Bogdanova, E., Garapach, I., Maslak, O., Esmedlyaeva, D., Dyakova, M., Yablonskiy, P., Ziganshin, R., Kovalchuk, S., Blum, N., Sonawane, S. H., Sonawane, A., … Shevtsov, M. (2024). Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis. Scientific Reports, 14(1), 4495. https://doi.org/10.1038/s41598-024-54992-z

Yun, B. D., Son, S. W., Choi, S. Y., Kuh, H. J., Oh, T.-J., & Park, J. K. (2021). Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha. International Journal of Molecular Sciences, 22(18), 9819. https://doi.org/10.3390/ijms22189819

Zhang, X., Xie, Q., Ye, Z., Li, Y., Che, Z., Huang, M., & Zeng, J. (2021). Mesenchymal Stem Cells and Tuberculosis: Clinical Challenges and Opportunities. Frontiers in Immunology, 12, 695278. https://doi.org/10.3389/fimmu.2021.695278

Zhong, C., Wang, G., Guo, M., Zhu, N., Chen, X., Yan, Y., Li, N., & Yu, W. (2024). The Role of Tumor Stem Cells in Colorectal Cancer Drug Resistance. Cancer Control, 31, 10732748241274196. https://doi.org/10.1177/10732748241274196

Author Biographies

Christine Verawaty Sibuea, Universitas HKBP Nommensen

Author Origin : Indonesia

Dina Octafrida Marpaung, Universitas HKBP Nommensen

Author Origin : Indonesia

Ervina Julien Sitanggang, Universitas HKBP Nommensen

Author Origin : Indonesia

Ade Pryta Simaremare, Universitas HKBP Nommensen

Author Origin : Indonesia

Cindy Destasya Masal, Universitas HKBP Nommensen

Author Origin : Indonesia

George Azriel Buala Nama Laia, Universitas HKBP Nommensen

Author Origin : Indonesia

Octora Angelica Violyn Tambunan, Universitas HKBP Nommensen

Author Origin : Indonesia

Wanda Lucia Samosir, Universitas HKBP Nommensen

Author Origin : Indonesia

Cici Kres Sidabalok, Universitas HKBP Nommensen

Author Origin : Indonesia

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How to Cite

Sibuea, C. V., Marpaung, D. O., Sitanggang, E. J., Simaremare, A. P., Masal, C. D., Laia, G. A. B. N., … Sidabalok, C. K. (2025). Encapsulated Mesenchymal Stem Cell as Regenerative Alternative for MDR-TB: A Gene Expression Analysis of ABCG2 Efflux. Jurnal Penelitian Pendidikan IPA, 11(8), 669–674. https://doi.org/10.29303/jppipa.v11i8.12040