Mesenchymal Stem Cells for Healing the Kidney

Mesenchymal Stem Cells for Healing the Kidney

According to a study by the GBD Chronic Kidney Disease Collaboration (2020), the incidence of chronic kidney disease (CKD) was 697·5 million or 9.1% in 2017: an increase of 29·3% from what was reported in 1990. The loss of lives due to CKD increased by 41·5% between 1990 and 2017! CKD is a risk factor for developing cardiovascular disease and hence is a global cause of concern.

The agents currently used in the clinic are not able to stall the damage to tissues seen in CKD. Another issue is the limited regenerative ability of the kidney that is not able to stop the fibrosis. This accounts for the global trend in morbidity and mortality due to CKD. Approaches to stall the kidney damage are being actively sort after. Promising results have been seen in several models of kidney disease using mesenchymal stem cells (MSCs). These results are accounted for by the ability of MSCs to secrete cytokines to modulate the immune system and secrete anti-fibrotic and anti-apoptotic factors to boost cell repair (Chung, 2019).

The” first-in-man dose-escalation study” published in 2017 showed the safety of intra-arterial infusion of autologous MSCs in Renovascular Disease. MSCs from the adipose tissue (105 or 2.5 × 105 cells/kg body weight) were administered to 14 patients along with standardized medical treatment. While the MSCs were well tolerated, an increase in renal blood flow that is normally lowered in the disease was observed 3 months after infusion that was not seen in controls who received only standardized medical treatment. Additionally, the glomerular filtration rate was stable due to stem cell treatment showing the safety and efficiency of MSCs for kidney disease.

In the case of kidney transplantation for end-stage renal disease patients, the administration of immunosuppressive agents is associated with serious adverse effects such as opportunistic infections and metabolic disorders. In the long term phase 1 study reported in Frontiers in immunology (2018), four living-donor kidney transplant patients were administered bone marrow-derived mesenchymal stromal cells. The MSCs were administered one day before transplant in 2 patients and at day 7 post-transplant in 2 patients along with basiliximab plus low-dose rabbit anti-thymocyte globulin (RATG) and low-dose cyclosporin (CsA)/mycophenolate mofetil (MMF). The graft was stable with no cancerous tissue formation or susceptibility to infections in all patients for the 5- to 7-year follow-up. 2 patients showed favorable T cell and B cell profiles; with even discontinuation of CsA in one of these patients. The safety of using MSCs to promote tolerance of grafts was hence shown opening up avenues for further studies (NCT00752479 and NCT02012153).

The efficacy and safety of MSCs continue to be shown in repeated studies to be extended to the realm of “difficult to treat” kidney disease.

 

References:

GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. DOI:https://doi.org/10.1016/S0140-6736(20)30045-3

Chung B. H. (2019). Use of mesenchymal stem cells for chronic kidney disease. Kidney research and clinical practice38(2), 131–134. https://doi.org/10.23876/j.krcp.19.051.

Saad, A., Dietz, A. B., Herrmann, S., Hickson, L. J., Glockner, J. F., McKusick, M. A., Misra, S., Bjarnason, H., Armstrong, A. S., Gastineau, D. A., Lerman, L. O., & Textor, S. C. (2017). Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular Disease. Journal of the American Society of Nephrology : JASN28(9), 2777–2785. https://doi.org/10.1681/ASN.2017020151

Perico, N., Casiraghi, F., Todeschini, M., Cortinovis, M., Gotti, E., Portalupi, V., Mister, M., Gaspari, F., Villa, A., Fiori, S., Introna, M., Longhi, E., & Remuzzi, G. (2018). Long-Term Clinical and Immunological Profile of Kidney Transplant Patients Given Mesenchymal Stromal Cell Immunotherapy. Frontiers in immunology9, 1359. https://doi.org/10.3389/fimmu.2018.01359

Bochon, B., Kozubska, M., Surygała, G., Witkowska, A., Kuźniewicz, R., Grzeszczak, W., & Wystrychowski, G. (2019). Mesenchymal Stem Cells-Potential Applications in Kidney Diseases. International journal of molecular sciences20(10), 2462. https://doi.org/10.3390/ijms20102462

 

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