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Kidney Failure

Mesenchymal Stem Cells Therapy for Patients with Renal Failure at Swiss Medica Clinic

Renal failure is a condition that develops due to inability of the kidney to adequately filter waste products from the blood. There are two main forms of renal failure namely acute kidney injury and chronic kidney disease.

Acute kidney injury (AKI) represents a complex clinical syndrome which is characterized by acute tubular injury leading to rapid renal dysfunction. It is common in hospitalized patients especially in those who have chronic kidney disease, diabetes, and vascular diseases. The major cause of AKI is considered to be ischemia and reperfusion injury[1,2].

Inflammation,  oxidative  stress and as a result excessive deposition of extracellular matrix due to intensive fibroblast proliferation represent a major events which take place after AKI and contribute to end-stage kidney disease development[3].

Currently no definitive therapy for AKI exists. Only supportive treatment is now available. Unfortunately, these approach doesn't significantly improve the outcomes of  such patients.     AKI remains a major cause of in-hospital morbidity and mortality[4,5].

Chronic kidney disease (CKD) represents a progressive loss in renal function over a period of months or years. CKD is a major risk factor for end stage renal disease and cardiovascular disease[6]. Therefore, the main goal of the treatment  is slowing the progression of disease. The last stage of CKD requires renal replacement therapy such as different forms of dialysis or kidney transplantation[7].

Mesenchymal stem cells(MSCs) represent a promising therapeutic approach in the treatment of patients with renal failure. They are able to target the whole cascade of pathogenic events that occurs in acute kidney injury, as well as MSCs slow the progression of chronic kidney disease. It was demonstrated that MSCs possess potent nephroprotective action that is mainly realized through paracrine mechanisms and leads to restoration of kidney function after injury[8]. More specifically, MSCs secrete a broad spectrum of highly active substances such as growth factors, cytokines, and chemokines. Due to these bioactive factors MSCs inhibit apoptosis of the cells as well as fibrosis(the formation of excess fibrous connective tissue in an organ) leading to restriction the damaged area. Moreover, they stimulate angiogenesis(new blood vessels formation) promoting to the recovery of blood supply as well as MSCs recruit own stem cells to the site of injury engaging them to the repair of tissues. In addition, attenuation of oxidative stress occurs due to the action of MSCs. It is necessary to mention that MSCs exert powerful immunomodulatory and anti-inflammatory effects[9,10]. It is considered that the microenvironment of damaged tissues produces factors that attract stem cells to the site of injury[11]. MSCs have two homing receptors such as CXCR4 for stromal cell-derived factor 1(SDF-1) and CD44 for hyaluronic acid that facilitate their recruitment to the sites of injury in the kidney as both the chemokine SDF-1 and hyaluronic acid are significantly increased in the damaged kidney[12,13]. Thus, due to complex paracrine actions MSCs promote to rapid and complete repair the functioning of the injured kidney.

In 2012 Tögel F.E. et al. reported the results of clinical trial in which cardiac surgery patients with high risk of postoperative AKI development were treated with mesenchymal stem cells.  The follow-up period was 3 years. The obtained data showed that MSCs therapy is safe and promote to kidney function preservation. None of the patients required dialysis during all observational period. In addition, MSCs treatment led to reduction the duration of hospital stay  as well as need for readmission[14].

It is necessary to mention the results of systematic review and meta-analysis of preclinical studies in which the efficacy of cell-based therapy in CKD was evaluated. According to the obtained data stem cells treatment improves impaired renal function and structure as well as it leads to the reduction of CKD progression[15].  

 

References

  1. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 2006;17:1503-1520; PMID: 16707563 DOI: 10.1681/ASN.2006010017
  2. Chertow G.M., Burdick E., Honour M. et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16(11):3365-3370
  3. Ishani A., Xue J.L., Himmelfarb J. et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 2009; 20: 223-228; PMID: 19020007 DOI: 10.1681/ASN.2007080837
  4. Palevsky P.M., Zhang J.H., O’Connor T.Z. et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008; 359(1):7-20
  5. Lameire N.H., Bagga A., Cruz D. et al. Acute kidney injury: an increasing global concern. Lancet 2013; 382: 170-179; PMID: 23727171 DOI:10.1016/S0140-6736(13)60647-9
  6. Foley R.N., Parfrey P.S., Sarnak M.J. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis.1998;32(5 Suppl 3):112-9.
  7. Papazova D.A., Oosterhuis N.R., Gremmels H. et al. Cell-based therapies for experimental chronic kidney disease: a systematic review and meta-analysis. Dis Model Mech. 2015;8(3):281-93. doi: 10.1242/dmm.017699.
  8. Wise A.F., Ricardo S.D. Mesenchymal stem cells in kidney inflammation and repair. Nephrology (Carlton) 2012; 17: 1-10; PMID: 21777348 DOI: 10.1111/j.1440-1797.2011.01501
  1. Chen L., Tredget E.E., Wu P.Y. et al. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One 2008;  3:e1886.
  2. Valle-Prieto A., Conget P.A. Human mesenchymal stem cells efficiently manage oxidative stress. StemCells Dev 2010; 19:1885–1893.
  3. Caplan A.I., Dennis J.E. Mesenchymal stem cells as trophic mediators. J Cell Biochem2006;98:1076-84.
  4. Togel F., Isaac J., Hu Z. et al. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005;67(5):1772-1784.
  5. Herrera M.B., Bussolati B., Bruno S. et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int. 2007;72(4):430-441
  6. Tögel F.E., Westenfelder C. Kidney protection and regeneration following acute injury: progress through stem cell therapy. Am J Kidney Dis2012; 60: 1012-1022; PMID: 23036928 DOI:10.1053/j.ajkd.2012.08.034
  7. Papazova D.A., Oosterhuis N.R., Gremmels H. et al. Cell-based therapies for experimental chronic kidney disease: a systematic review and meta-analysis. Dis Model Mech. 2015;8(3):281-93. doi: 10.1242/dmm.017699. Epub 2015 Jan 29.