title: Uremic toxins impair human bone marrow-derived mesenchymal stem cells functionality in vitro.
abstract: Mesenchymal stem cells (MSCs) are becoming therapeutic agents of interest in many areas of medicine, including renal diseases and kidney transplantations. However, the effect of uremia on cell properties is still unclear. Therefore, we examined the in vitro influence of uremic toxins, p-cresol (PC) and indoxyl sulfate (IS), on human bone marrow-derived MSC functionality. Cultured MSCs were treated with PC and IS at concentrations corresponding to subsequent stages of chronic kidney disease. Cell viability was characterized by metabolic activity (MTT assay) and proliferation rate (BrdU assay). Apoptosis (Annexin V test) and cell membrane damage (LDH assay) were also tested. MSC secretory properties were determined by measuring cytokine/growth factor levels in media from toxin-treated cells (ELISA). Uremic concentrations of PC and IS resulted in significant inhibition of MSC metabolic activity and proliferation. Toxins did not induce apoptosis, but damaged cell membranes. MSC paracrine activity was also altered - a decrease of VEGF and TGF-β1 levels and an increase in IGF-1 and IL-8 secretion was detected. Presented data indicate a negative influence of uremic toxins on functional characteristics of human bone marrow-derived MSCs. Therefore, their use as autologous therapeutic agents for kidney disease may be questionable and requires further investigations. The observed phenomenon may be attributable to many other MSC therapies, because of the high prevalence of chronic kidney disease in adult population.
authors.affiliation: Department of Immunology, Transplantology and Internal Diseases, Transplantation Institute, Warsaw Medical University, Poland. Electronic address: marta.idziak@yahoo.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Idziak
authors.affiliation: Department of Orthopaedy and Traumatology of the Motor System, Warsaw Medical University, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Pędzisz
authors.affiliation: Department of Immunology, Transplantology and Internal Diseases, Transplantation Institute, Warsaw Medical University, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Burdzińska
authors.affiliation: Department of Immunology, Transplantology and Internal Diseases, Transplantation Institute, Warsaw Medical University, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Gala
authors.affiliation: Department of Immunology, Transplantology and Internal Diseases, Transplantation Institute, Warsaw Medical University, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Pączek
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003408:Cresols / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007200:Indican / Q000378:metabolism / Q000633:toxicity*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014511:Uremia / Q000378:metabolism / Q000473:pathology*
chemical_list: D003408:Cresols; C032538:4-cresol; D007200:Indican
keywords: Indoxyl sulfate; Kidney regeneration; Mesenchymal stem cells; Uremic toxicity; p-Cresol