The Characteristics of Umbilical Cord Derived Mesenchymal Stem Cell/UCMSC from Macaca fascicularis and Its Secretome Under Hypoxic Conditions
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Jun 30, 2024
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Abstract
Mesenchymal Stem Cell (MSC) secretome has potential as a neuroprotective and neuroregenerative agent. It can have effects due to its paracrine factors, such as Brain Derived Neurotrophic Factor (BDNF) and Stromal-Cell Derived Factor-1 (SDF-1) which can be induced with hypoxia preconditioning. This compound may play a role in the treatment of neurological diseases. Stroke has become a neurological disease that contributes to high rates of mortality and morbidity worldwide. There have been several pre-clinical trials on animal stroke models using MSC secretomes from rats and humans, but no studies have been conducted on Non-Human Primate, such as Macaca fascicularis. This species has been widely used in biomedical research and part of it can be utilized for such studies which will reduce the cost of using human MSC. The results of this study, Umbilical Cord (UC)-MSCs of Macaca fascicularis have been successfully cultured and characterized in terms of phenotypic and differentiation. Hypoxia precondition was able to induce BDNF secretion up to 264 pg/mL and SDF-1 up to 666 pg/mL in the UCMSC secretome. Hypoxic preconditioning with 3% oxygen can induce the most optimal BDNF and SDF-1 secretion, compared to 1% and 5% hypoxia.
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References
Brahimi-Horn, M. C., & Pouysségur, J. (2007). Oxygen, a source of life and stress. In FEBS Letters (Vol. 581, Issue 19, pp. 3582–3591). https://doi.org/10.1016/j.febslet.2007.06.018
Carreau, A., Hafny-Rahbi, B. El, Matejuk, A., Grillon, C., & Kieda, C. (2011). Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. Journal of Cellular and Molecular Medicine, 15(6), 1239–1253. https://doi.org/10.1111/j.1582-4934.2011.01258.x
Chance, K. S., & Hickey, J. V. (1982). The Clinical Practice of Neurological and Neurosurgical Nursing. In The American Journal of Nursing (Vol. 82, Issue 3). https://doi.org/10.2307/3462952
Chen, J., Crawford, R., Chen, C., & Xiao, Y. (2013). The key regulatory roles of the PI3K/Akt signaling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration. Tissue Engineering - Part B: Reviews, 19(6), 516–528. https://doi.org/10.1089/ten.teb.2012.0672
Cheng, X., Wang, H., Zhang, X., Zhao, S., Zhou, Z., Mu, X., Zhao, C., & Teng, W. (2017). The role of SDF-1/CXCR4/CXCR7 in neuronal regeneration after cerebral ischemia. Frontiers in Neuroscience, 11(OCT), 1–13. https://doi.org/10.3389/fnins.2017.00590
Chester, K. W., Corrigan, M., Schoeffler, J. M., Shah, M., Toy, F., Purdon, B., & Dillon, G. M. (2019). Making a case for the right ‘-ase’ in acute ischemic stroke: alteplase, tenecteplase, and reteplase. Expert Opinion on Drug Safety, 18(2), 87–96. https://doi.org/10.1080/14740338.2019.1573985
Cunningham, C. J., Redondo-Castro, E., & Allan, S. M. (2018). The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke. Journal of Cerebral Blood Flow and Metabolism, 38(8), 1276–1292. https://doi.org/10.1177/0271678X18776802
da Silva, A. V., Serrenho, I., Araújo, B., Carvalho, A. M., & Baltazar, G. (2023). Secretome as a Tool to Treat Neurological Conditions: Are We Ready? International Journal of Molecular Sciences, 24(22). https://doi.org/10.3390/ijms242216544
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315–317. https://doi.org/10.1080/14653240600855905
Giovannelli, L., Bari, E., Jommi, C., Tartara, F., Armocida, D., Garbossa, D., Cofano, F., Torre, M. L., & Segale, L. (2023). Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access. Bioactive Materials, 29(June), 16–35. https://doi.org/10.1016/j.bioactmat.2023.06.013
Haque, N., Rahman, M. T., Abu Kasim, N. H., & Alabsi, A. M. (2013). Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy. The Scientific World Journal, 2013. https://doi.org/10.1155/2013/632972
Haupt, M., Gerner, S. T., Bähr, M., & Doeppner, T. R. (2023). Neuroprotective Strategies for Ischemic Stroke—Future Perspectives. International Journal of Molecular Sciences, 24(5). https://doi.org/10.3390/ijms24054334
Janowski, M. (2009). Functional diversity of SDF-1 splicing variants. Cell Adhesion and Migration, 3(3), 243–249. https://doi.org/10.4161/cam.3.3.8260
Johnson, C. O., Nguyen, M., Roth, G. A., Nichols, E., Alam, T., Abate, D., Abd-Allah, F., Abdelalim, A., Abraha, H. N., Abu-Rmeileh, N. M., Adebayo, O. M., Adeoye, A. M., Agarwal, G., Agrawal, S., Aichour, A. N., Aichour, I., Aichour, M. T. E., Alahdab, F., Ali, R., … Murray, C. J. L. (2019). Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(5), 439–458. https://doi.org/10.1016/S1474-4422(19)30034-1
Kaneko, S., & Takamatsu, K. (2012). Cell Handling and Culture Under Controlled Oxygen Concentration. Biomedical Tissue Culture. https://doi.org/10.5772/52112
Kementrian Kesehatan Republik Indonesia/Kemenkes RI. (2018). Laporan_Nasional_RKD2018_FINAL.pdf. In Badan Penelitian dan Pengembangan Kesehatan (p. 674). http://labdata.litbang.kemkes.go.id/images/download/laporan/RKD/2018/Laporan_Nasional_RKD2018_FINAL.pdf
Konala, V. B. R., Bhonde, R., & Pal, R. (2020). Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. In Vitro Cellular and Developmental Biology - Animal, 56(9), 689–700. https://doi.org/10.1007/s11626-020-00501-1
Kowianski, P., Lietzau, G., Czuba, E., Waskow, M., Steliga, A., & Janusz, M. (2917). BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-017-0510-4
Krishnan, A., Kaleka, G., Emerson, S., Sovak, G., Simmons, H., Brunner, K., Schalk, D., Sledge, J., Hoggatt, A., & Nesathurai, S. (2022). Anatomical and Radiological Description of the <i>Macaca fascicularis</i> Spine in Comparison with the Human Spine. Open Journal of Veterinary Medicine, 12(12), 171–186. https://doi.org/10.4236/ojvm.2022.1212014
Liu, W., Wang, X., O’Connor, M., Wang, G., & Han, F. (2020). Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities. Neural Plasticity, 2020. https://doi.org/10.1155/2020/1969482
Majumdar, D., Bhonde, R., & Datta, I. (2013). Influence of ischemic microenvironment on human Wharton’s Jelly mesenchymal stromal cells. Placenta, 34(8), 642–649. https://doi.org/10.1016/j.placenta.2013.04.021
Mariya, S. S., Dewi, F. N., Villiandra, Paramastri, Y. A., Iskandriati, D., Saepuloh, U., Hayes, E., Pamungkas, J., & Sajuthi, D. (2019). Isolation and characterization of c-c chemokine ligand 7 (Ccl7) in cynomolgus macaques. HAYATI Journal of Biosciences, 26(3), 129–132. https://doi.org/10.4308/hjb.26.3.129
Mastrolia, I., Foppiani, E. M., Murgia, A., Candini, O., Samarelli, A. V., Grisendi, G., Veronesi, E., Horwitz, E. M., & Dominici, M. (2019). Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review. Stem Cells Translational Medicine, 8(11), 1135–1148. https://doi.org/10.1002/sctm.19-0044
Mohyeldin, A., Garzón-Muvdi, T., & Quiñones-Hinojosa, A. (2010). Oxygen in stem cell biology: A critical component of the stem cell niche. Cell Stem Cell, 7(2), 150–161. https://doi.org/10.1016/j.stem.2010.07.007
Nakazawa, M. S., Keith, B., & Simon, M. C. (2016). Oxygen availability and metabolic adaptations. Nature Reviews Cancer, 16(10), 663–673. https://doi.org/10.1038/nrc.2016.84
Patil, S., Fageeh, H. N., Fageeh, H. I., Ibraheem, W., Alshehri, A. S., Al-Brakati, A., Almoammar, S., Almagbol, M., Dewan, H., Khan, S. S., Baeshen, H. A., Patil, V. R., Raj, A. T., & Bhandi, S. (2022). Hypoxia, a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion. Saudi Journal of Biological Sciences, 29(5), 3568–3576. https://doi.org/10.1016/j.sjbs.2022.02.039
Pinho, A. G., Cibrão, J. R., Silva, N. A., Monteiro, S., & Salgado, A. J. (2020). Cell secretome: Basic insights and therapeutic opportunities for CNS disorders. Pharmaceuticals, 13(2), 1–18. https://doi.org/10.3390/ph13020031
Pulido-Escribano, V., Torrecillas-Baena, B., Camacho-Cardenosa, M., Dorado, G., Gálvez-Moreno, M. Á., & Casado-Díaz, A. (2022). Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles. World Journal of Stem Cells, 14(7), 453–472. https://doi.org/10.4252/wjsc.v14.i7.453
Rinendyaputri, R., Noviantari, A., Zainuri, M., Nikmah, U. A., Dany, F., & Intan, P. R. (2023). Secretion of growth factor in conditioned medium rat bone marrow-derived mesenchymal stem cells (CM-rBMMSC). AIP Conference Proceedings, 2694(July 2019). https://doi.org/10.1063/5.0118570
Segeritz, C. P., & Vallier, L. (2017). Cell Culture: Growing Cells as Model Systems In Vitro. In Basic Science Methods for Clinical Researchers. Elsevier Inc. https://doi.org/10.1016/B978-0-12-803077-6.00009-6
Sidharta, V. M., Herningtyas, E. H., Lagonda, C. A., Fauza, D., Kusnadi, Y., Susilowati, R., & Partadiredja, G. (2018). High VEGF level is produced by human umbilical cord- mesenchymal stem cells (hUC-MSCs) in amino acid-rich medium and under hypoxia condition. Indonesian Biomedical Journal, 10(3), 222–230. https://doi.org/10.18585/inabj.v10i3.457
Sjöstedt, S., Rooth, G., & Caligara, F. (1960). The oxygen tension of the blood in the umbilical cord and the intervillous space. Archives of Disease in Childhood, 35(184), 529–533. https://doi.org/10.1136/adc.35.184.529
Stamati, K., Mudera, V., & Cheema, U. (2015). Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering. Journal of Tissue Engineering. https://doi.org/10.1177/2041731411432365
Theodoridis, T., & Kraemer, J. (2023). Minimum Essential Medium Specification. 3–5. https://www.thermofisher.com/id/en/home/life-science/cell-culture/mammalian-cell-culture/cell-culture-media/mem.html
Turlo, A. J., Hammond, D. E., Ramsbottom, K. A., Soul, J., Gillen, A., McDonald, K., & Peffers, M. J. (2023). Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age. Stem Cells (Dayton, Ohio), 41(11), 1047–1059. https://doi.org/10.1093/stmcls/sxad060
Widowati, W., Noverina, R., Ayuningtyas, W., Kurniawan, D., Arumwardana, S., Kusuma, H. S. W., Rizal, R., Laksmitawati, D. R., Rinendyaputri, R., Rilianawati, R., & Faried, A. (2022). Potential of Conditioned Medium of hATMSCs in Aging Cells Model. HAYATI Journal of Biosciences, 29(3), 378–388. https://doi.org/10.4308/hjb.29.3.378-388
World Health Organization. (2024). Life expectancy. Data.Who.Int, Indonesia [Country Overview]. https://data.who.int/countries/360
Yang, Y., Wu, Y., Yang, D., Neo, S. H., Kadir, N. D., Goh, D., Tan, J. X., Denslin, V., Lee, E. H., & Yang, Z. (2023). Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles. Bioactive Materials, 27(March), 98–112. https://doi.org/10.1016/j.bioactmat.2023.03.017
Yu, F. X., Hu, W. J., He, B., Zheng, Y. H., Zhang, Q. Y., & Chen, L. (2015). Bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion. World Journal of Surgical Oncology, 13(1), 1–7. https://doi.org/10.1186/s12957-015-0465-1
Zhang, Y., Ma, L., Su, Y., Su, L., Lan, X., Wu, D., Han, S., Li, J., Kvederis, L., Corey, S., Borlongan, C. V., & Ji, X. (2019). Hypoxia conditioning enhances neuroprotective effects of aged human bone marrow mesenchymal stem cell-derived conditioned medium against cerebral ischemia in vitro. In Brain Research (Vol. 1725). Elsevier B.V. https://doi.org/10.1016/j.brainres.2019.146432
Zhao, H., Alam, A., San, C. Y., Eguchi, S., Chen, Q., Lian, Q., & Ma, D. (2017). Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments. Brain Research, 1665, 1–21. https://doi.org/10.1016/j.brainres.2017.03.029
Carreau, A., Hafny-Rahbi, B. El, Matejuk, A., Grillon, C., & Kieda, C. (2011). Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. Journal of Cellular and Molecular Medicine, 15(6), 1239–1253. https://doi.org/10.1111/j.1582-4934.2011.01258.x
Chance, K. S., & Hickey, J. V. (1982). The Clinical Practice of Neurological and Neurosurgical Nursing. In The American Journal of Nursing (Vol. 82, Issue 3). https://doi.org/10.2307/3462952
Chen, J., Crawford, R., Chen, C., & Xiao, Y. (2013). The key regulatory roles of the PI3K/Akt signaling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration. Tissue Engineering - Part B: Reviews, 19(6), 516–528. https://doi.org/10.1089/ten.teb.2012.0672
Cheng, X., Wang, H., Zhang, X., Zhao, S., Zhou, Z., Mu, X., Zhao, C., & Teng, W. (2017). The role of SDF-1/CXCR4/CXCR7 in neuronal regeneration after cerebral ischemia. Frontiers in Neuroscience, 11(OCT), 1–13. https://doi.org/10.3389/fnins.2017.00590
Chester, K. W., Corrigan, M., Schoeffler, J. M., Shah, M., Toy, F., Purdon, B., & Dillon, G. M. (2019). Making a case for the right ‘-ase’ in acute ischemic stroke: alteplase, tenecteplase, and reteplase. Expert Opinion on Drug Safety, 18(2), 87–96. https://doi.org/10.1080/14740338.2019.1573985
Cunningham, C. J., Redondo-Castro, E., & Allan, S. M. (2018). The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke. Journal of Cerebral Blood Flow and Metabolism, 38(8), 1276–1292. https://doi.org/10.1177/0271678X18776802
da Silva, A. V., Serrenho, I., Araújo, B., Carvalho, A. M., & Baltazar, G. (2023). Secretome as a Tool to Treat Neurological Conditions: Are We Ready? International Journal of Molecular Sciences, 24(22). https://doi.org/10.3390/ijms242216544
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315–317. https://doi.org/10.1080/14653240600855905
Giovannelli, L., Bari, E., Jommi, C., Tartara, F., Armocida, D., Garbossa, D., Cofano, F., Torre, M. L., & Segale, L. (2023). Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access. Bioactive Materials, 29(June), 16–35. https://doi.org/10.1016/j.bioactmat.2023.06.013
Haque, N., Rahman, M. T., Abu Kasim, N. H., & Alabsi, A. M. (2013). Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy. The Scientific World Journal, 2013. https://doi.org/10.1155/2013/632972
Haupt, M., Gerner, S. T., Bähr, M., & Doeppner, T. R. (2023). Neuroprotective Strategies for Ischemic Stroke—Future Perspectives. International Journal of Molecular Sciences, 24(5). https://doi.org/10.3390/ijms24054334
Janowski, M. (2009). Functional diversity of SDF-1 splicing variants. Cell Adhesion and Migration, 3(3), 243–249. https://doi.org/10.4161/cam.3.3.8260
Johnson, C. O., Nguyen, M., Roth, G. A., Nichols, E., Alam, T., Abate, D., Abd-Allah, F., Abdelalim, A., Abraha, H. N., Abu-Rmeileh, N. M., Adebayo, O. M., Adeoye, A. M., Agarwal, G., Agrawal, S., Aichour, A. N., Aichour, I., Aichour, M. T. E., Alahdab, F., Ali, R., … Murray, C. J. L. (2019). Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(5), 439–458. https://doi.org/10.1016/S1474-4422(19)30034-1
Kaneko, S., & Takamatsu, K. (2012). Cell Handling and Culture Under Controlled Oxygen Concentration. Biomedical Tissue Culture. https://doi.org/10.5772/52112
Kementrian Kesehatan Republik Indonesia/Kemenkes RI. (2018). Laporan_Nasional_RKD2018_FINAL.pdf. In Badan Penelitian dan Pengembangan Kesehatan (p. 674). http://labdata.litbang.kemkes.go.id/images/download/laporan/RKD/2018/Laporan_Nasional_RKD2018_FINAL.pdf
Konala, V. B. R., Bhonde, R., & Pal, R. (2020). Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. In Vitro Cellular and Developmental Biology - Animal, 56(9), 689–700. https://doi.org/10.1007/s11626-020-00501-1
Kowianski, P., Lietzau, G., Czuba, E., Waskow, M., Steliga, A., & Janusz, M. (2917). BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-017-0510-4
Krishnan, A., Kaleka, G., Emerson, S., Sovak, G., Simmons, H., Brunner, K., Schalk, D., Sledge, J., Hoggatt, A., & Nesathurai, S. (2022). Anatomical and Radiological Description of the <i>Macaca fascicularis</i> Spine in Comparison with the Human Spine. Open Journal of Veterinary Medicine, 12(12), 171–186. https://doi.org/10.4236/ojvm.2022.1212014
Liu, W., Wang, X., O’Connor, M., Wang, G., & Han, F. (2020). Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities. Neural Plasticity, 2020. https://doi.org/10.1155/2020/1969482
Majumdar, D., Bhonde, R., & Datta, I. (2013). Influence of ischemic microenvironment on human Wharton’s Jelly mesenchymal stromal cells. Placenta, 34(8), 642–649. https://doi.org/10.1016/j.placenta.2013.04.021
Mariya, S. S., Dewi, F. N., Villiandra, Paramastri, Y. A., Iskandriati, D., Saepuloh, U., Hayes, E., Pamungkas, J., & Sajuthi, D. (2019). Isolation and characterization of c-c chemokine ligand 7 (Ccl7) in cynomolgus macaques. HAYATI Journal of Biosciences, 26(3), 129–132. https://doi.org/10.4308/hjb.26.3.129
Mastrolia, I., Foppiani, E. M., Murgia, A., Candini, O., Samarelli, A. V., Grisendi, G., Veronesi, E., Horwitz, E. M., & Dominici, M. (2019). Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review. Stem Cells Translational Medicine, 8(11), 1135–1148. https://doi.org/10.1002/sctm.19-0044
Mohyeldin, A., Garzón-Muvdi, T., & Quiñones-Hinojosa, A. (2010). Oxygen in stem cell biology: A critical component of the stem cell niche. Cell Stem Cell, 7(2), 150–161. https://doi.org/10.1016/j.stem.2010.07.007
Nakazawa, M. S., Keith, B., & Simon, M. C. (2016). Oxygen availability and metabolic adaptations. Nature Reviews Cancer, 16(10), 663–673. https://doi.org/10.1038/nrc.2016.84
Patil, S., Fageeh, H. N., Fageeh, H. I., Ibraheem, W., Alshehri, A. S., Al-Brakati, A., Almoammar, S., Almagbol, M., Dewan, H., Khan, S. S., Baeshen, H. A., Patil, V. R., Raj, A. T., & Bhandi, S. (2022). Hypoxia, a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion. Saudi Journal of Biological Sciences, 29(5), 3568–3576. https://doi.org/10.1016/j.sjbs.2022.02.039
Pinho, A. G., Cibrão, J. R., Silva, N. A., Monteiro, S., & Salgado, A. J. (2020). Cell secretome: Basic insights and therapeutic opportunities for CNS disorders. Pharmaceuticals, 13(2), 1–18. https://doi.org/10.3390/ph13020031
Pulido-Escribano, V., Torrecillas-Baena, B., Camacho-Cardenosa, M., Dorado, G., Gálvez-Moreno, M. Á., & Casado-Díaz, A. (2022). Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles. World Journal of Stem Cells, 14(7), 453–472. https://doi.org/10.4252/wjsc.v14.i7.453
Rinendyaputri, R., Noviantari, A., Zainuri, M., Nikmah, U. A., Dany, F., & Intan, P. R. (2023). Secretion of growth factor in conditioned medium rat bone marrow-derived mesenchymal stem cells (CM-rBMMSC). AIP Conference Proceedings, 2694(July 2019). https://doi.org/10.1063/5.0118570
Segeritz, C. P., & Vallier, L. (2017). Cell Culture: Growing Cells as Model Systems In Vitro. In Basic Science Methods for Clinical Researchers. Elsevier Inc. https://doi.org/10.1016/B978-0-12-803077-6.00009-6
Sidharta, V. M., Herningtyas, E. H., Lagonda, C. A., Fauza, D., Kusnadi, Y., Susilowati, R., & Partadiredja, G. (2018). High VEGF level is produced by human umbilical cord- mesenchymal stem cells (hUC-MSCs) in amino acid-rich medium and under hypoxia condition. Indonesian Biomedical Journal, 10(3), 222–230. https://doi.org/10.18585/inabj.v10i3.457
Sjöstedt, S., Rooth, G., & Caligara, F. (1960). The oxygen tension of the blood in the umbilical cord and the intervillous space. Archives of Disease in Childhood, 35(184), 529–533. https://doi.org/10.1136/adc.35.184.529
Stamati, K., Mudera, V., & Cheema, U. (2015). Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering. Journal of Tissue Engineering. https://doi.org/10.1177/2041731411432365
Theodoridis, T., & Kraemer, J. (2023). Minimum Essential Medium Specification. 3–5. https://www.thermofisher.com/id/en/home/life-science/cell-culture/mammalian-cell-culture/cell-culture-media/mem.html
Turlo, A. J., Hammond, D. E., Ramsbottom, K. A., Soul, J., Gillen, A., McDonald, K., & Peffers, M. J. (2023). Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age. Stem Cells (Dayton, Ohio), 41(11), 1047–1059. https://doi.org/10.1093/stmcls/sxad060
Widowati, W., Noverina, R., Ayuningtyas, W., Kurniawan, D., Arumwardana, S., Kusuma, H. S. W., Rizal, R., Laksmitawati, D. R., Rinendyaputri, R., Rilianawati, R., & Faried, A. (2022). Potential of Conditioned Medium of hATMSCs in Aging Cells Model. HAYATI Journal of Biosciences, 29(3), 378–388. https://doi.org/10.4308/hjb.29.3.378-388
World Health Organization. (2024). Life expectancy. Data.Who.Int, Indonesia [Country Overview]. https://data.who.int/countries/360
Yang, Y., Wu, Y., Yang, D., Neo, S. H., Kadir, N. D., Goh, D., Tan, J. X., Denslin, V., Lee, E. H., & Yang, Z. (2023). Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles. Bioactive Materials, 27(March), 98–112. https://doi.org/10.1016/j.bioactmat.2023.03.017
Yu, F. X., Hu, W. J., He, B., Zheng, Y. H., Zhang, Q. Y., & Chen, L. (2015). Bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion. World Journal of Surgical Oncology, 13(1), 1–7. https://doi.org/10.1186/s12957-015-0465-1
Zhang, Y., Ma, L., Su, Y., Su, L., Lan, X., Wu, D., Han, S., Li, J., Kvederis, L., Corey, S., Borlongan, C. V., & Ji, X. (2019). Hypoxia conditioning enhances neuroprotective effects of aged human bone marrow mesenchymal stem cell-derived conditioned medium against cerebral ischemia in vitro. In Brain Research (Vol. 1725). Elsevier B.V. https://doi.org/10.1016/j.brainres.2019.146432
Zhao, H., Alam, A., San, C. Y., Eguchi, S., Chen, Q., Lian, Q., & Ma, D. (2017). Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments. Brain Research, 1665, 1–21. https://doi.org/10.1016/j.brainres.2017.03.029