Harnessing Stem Cells for Kidney Regeneration : Progresses and Challenges in Clinical Translation

Ni Luh Wisma Eka Yanti; Anak Agung Dita Hendrawan; Maqfirah Muryanifa

doi:10.62951/ijhsb.v2i1.282

Authors

Ni Luh Wisma Eka Yanti Universitas Bali Dwipa
Anak Agung Dita Hendrawan Universitas Bali Dwipa
Maqfirah Muryanifa Universitas Bali Dwipa

DOI:

https://doi.org/10.62951/ijhsb.v2i1.282

Keywords:

stem cells, mesenchymal stem cells, kidney regeneration, clinical application

Abstract

The prevalence of chronic kidney disease is increasing worldwide and is considered a burden for health care systems and patients. However, there are only a few treatment options, and in most cases, the end-stage of the disease requires renal replacement. Stem cell-based therapy has gained popularity as a cutting-edge strategy in the field of regenerative nephrology. Numerous clinical studies on evaluating stem cells safety and tolerability have been carried out, leading to clinical translation of stem cells for kidney regeneration. This study will focues on progresses of recent clinical trials on stem cell therapy for various kidney diseases, while also highlighting key challenges in clinical translation and future directions in the field of regenerative nephrology.

Downloads

Download data is not yet available.

References

Abumoawad, A., Saad, A., Ferguson, C. M., Eirin, A., Herrmann, S. M., Hickson, L. T. J., Goksu, B. B., Bendel, E., Misra, S., Glockner, J., Dietz, A. B., Lerman, L. O., & Textor, S. C. (2020). In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure. Kidney International, 97(4), 793–804. https://doi.org/10.1016/j.kint.2019.11.022

An, X., Liao, G., Chen, Y., Luo, A., Liu, J., Yuan, Y., Li, L., Yang, L., Wang, H., Liu, F., Yang, G., Yi, S., Li, Y., Cheng, J., & Lu, Y. (2019). Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model. Stem Cell Research & Therapy, 10(1), 363. https://doi.org/10.1186/s13287-019-1401-z

Carstens, M. H., García, N., Mandayam, S., Workeneh, B., Pastora, I., Calderón, C., Bertram, K. A., & Correa, D. (2023). Safety of stromal vascular fraction cell therapy for chronic kidney disease of unknown cause (Mesoamerican nephropathy). Stem Cells Translational Medicine, 12(1), 7–16. https://doi.org/10.1093/stcltm/szac080

Casiraghi, F., Perico, N., & Remuzzi, G. (2018). Mesenchymal stromal cells for tolerance induction in organ transplantation. Human Immunology, 79(5), 304–313. https://doi.org/10.1016/j.humimm.2017.12.008

Casiraghi, F., Perico, N., Cortinovis, M., & Remuzzi, G. (2016). Mesenchymal stromal cells in renal transplantation: Opportunities and challenges. Nature Reviews Nephrology, 12(4), 241–253. https://doi.org/10.1038/nrneph.2016.7

Centers for Disease Control and Prevention. (n.d.). Chronic kidney disease (CKD) surveillance system: 2021. Centers for Disease Control and Prevention. Retrieved from https://nccd.cdc.gov/ckd/default.aspx

Deng, D., Zhang, P., Guo, Y., & Lim, T. O. (2017). A randomized double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis. Annals of the Rheumatic Diseases, 76(8), 1436–1439. https://doi.org/10.1136/annrheumdis-2017-211073

Eirin, A., Zhu, X.-Y., Jonnada, S., Lerman, A., van Wijnen, A. J., & Lerman, L. O. (2018). Mesenchymal stem cell-derived extracellular vesicles improve the renal microvasculature in metabolic renovascular disease in swine. Cell Transplantation, 27(7), 1080–1095. https://doi.org/10.1177/0963689718780942

Hill, N. R., Fatoba, S. T., Oke, J. L., Hirst, J. A., O’Callaghan, C. A., Lasserson, D. S., & Hobbs, F. D. R. (2016). Global prevalence of chronic kidney disease – A systematic review and meta-analysis. PLOS ONE, 11(7), e0158765. https://doi.org/10.1371/journal.pone.0158765

Hoste, E. A. J., Kellum, J. A., Selby, N. M., Zarbock, A., Palevsky, P. M., Bagshaw, S. M., Goldstein, S. L., Cerdá, J., & Chawla, L. S. (2018). Global epidemiology and outcomes of acute kidney injury. Nature Reviews Nephrology, 14(10), 607–625. https://doi.org/10.1038/s41581-018-0052-0

Irazabal, M. V., Hickson, L. J., & Eirin, A. (2019). Mesenchymal stem cell–based therapy for chronic kidney disease. In A Roadmap to Non-Hematopoietic Stem Cell-Based Therapeutics (pp. 275–296). Elsevier. https://doi.org/10.1016/B978-0-12-811920-4.00011-2

Jager, K. J., Kovesdy, C., Langham, R., Rosenberg, M., Jha, V., & Zoccali, C. (2019). A single number for advocacy and communication—Worldwide more than 850 million individuals have kidney diseases. Kidney International, 96(5), 1048–1050. https://doi.org/10.1016/j.kint.2019.07.012

Kovesdy, C. P. (2022). Epidemiology of chronic kidney disease: An update 2022. Kidney International Supplements, 12(1), 7–11. https://doi.org/10.1016/j.kisu.2021.11.003

Lee, M. S., Lee, F. Y., Chen, Y. L., Sung, P. H., Chiang, H. J., Chen, K. H., Huang, T. H., Chen, Y. L., Chiang, J. Y., Yin, T. C., Chang, H. W., & Yip, H. K. (2017). Investigated the safety of intra-renal arterial transfusion of autologous CD34+ cells and time courses of creatinine levels, endothelial dysfunction biomarkers, and micro-RNAs in chronic kidney disease patients—Phase I clinical trial. Oncotarget, 8(11), 17750–17762. https://doi.org/10.18632/oncotarget.14831

Li, Y., Ricardo, S. D., & Samuel, C. S. (2022). Enhancing the therapeutic potential of mesenchymal stromal cell-based therapies with an anti-fibrotic agent for the treatment of chronic kidney disease. International Journal of Molecular Sciences, 23(11), 6035. https://doi.org/10.3390/ijms23116035

Makhlough, A., Shekarchian, S., Moghadasali, R., Einollahi, B., Dastgheib, M., Janbabaee, G., Hosseini, S. E., Falah, N., Abbasi, F., Baharvand, H., & Aghdami, N. (2018). Bone marrow–mesenchymal stromal cell infusion in patients with chronic kidney disease: A safety study with 18 months of follow-up. Cytotherapy, 20(5), 660–669. https://doi.org/10.1016/j.jcyt.2018.02.368

Makhlough, A., Shekarchian, S., Moghadasali, R., Einollahi, B., Hosseini, S. E., Jaroughi, N., Bolurieh, T., Baharvand, H., & Aghdami, N. (2017). Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients. Stem Cell Research and Therapy, 8(1), 1–11. https://doi.org/10.1186/s13287-017-0557-7

Makris, K., & Spanou, L. (2016). Acute kidney injury: Definition, pathophysiology, and clinical phenotypes. The Clinical Biochemist Reviews, 37(2), 85–98. http://www.ncbi.nlm.nih.gov/pubmed/28303073

Malekshahabi, T., Khoshdel Rad, N., Serra, A. L., & Moghadasali, R. (2019). Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions. Journal of Cellular Physiology, 234(8), 12451–12470. https://doi.org/10.1002/jcp.28094

Moghadasali, R., Hajinasrollah, M., Argani, H., Nassiri, S. M., Najarasl, M., Sodeifi, N., Baharvand, H., & Aghdami, N. (2015). Autologous transplantation of mesenchymal stromal cells tends to prevent progress of interstitial fibrosis in a rhesus Macaca mulatta monkey model of chronic kidney disease. Cytotherapy, 17(11), 1495–1505. https://doi.org/10.1016/j.jcyt.2015.06.006

Nagaishi, K., Mizue, Y., Chikenji, T., Otani, M., Nakano, M., Konari, N., & Fujimiya, M. (2016). Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes. Scientific Reports, 6(1), 34842. https://doi.org/10.1038/srep34842

Packham, D. K., Fraser, I. R., Kerr, P. G., & Segal, K. R. (2016). Allogeneic mesenchymal precursor cells (MPC) in diabetic nephropathy: A randomized, placebo-controlled, dose escalation study. EBioMedicine, 12, 263–269. https://doi.org/10.1016/j.ebiom.2016.09.011

Papazova, D. A., Oosterhuis, N. R., Gremmels, H., van Koppen, A., Joles, J. A., & Verhaar, M. C. (2015). Cell-based therapies for experimental chronic kidney disease: A systematic review and meta-analysis. Disease Models & Mechanisms. https://doi.org/10.1242/dmm.017699

Peired, A. J., Sisti, A., & Romagnani, P. (2016). Mesenchymal stem cell‐based therapy for kidney disease: A review of clinical evidence. Stem Cells International, 2016(1). https://doi.org/10.1155/2016/4798639

Perico, N., Remuzzi, G., Griffin, M. D., Cockwell, P., Maxwell, A. P., Casiraghi, F., Rubis, N., Peracchi, T., Villa, A., Todeschini, M., Carrara, F., Magee, B. A., Ruggenenti, P. L., Rota, S., Cappelletti, L., McInerney, V., Griffin, T. P., Islam, M. N., Introna, M., … O’Brien, T. (2023). Safety and preliminary efficacy of mesenchymal stromal cell (ORBCEL-M) therapy in diabetic kidney disease: A randomized clinical trial (NEPHSTROM). Journal of the American Society of Nephrology, 34(10), 1733–1751. https://doi.org/10.1681/ASN.0000000000000189