Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases

Abstract

BackgroundBio-products from stem/progenitor cells, such as extracellular vesicles, are likely a new promising approach for reprogramming resident cells in both acute and chronic kidney disease. Forty CKD patients stage III and IV (eGFR 15–60 mg/ml) have been divided into two groups; twenty patients as treatment group “A” and twenty patients as a matching placebo group “B”. Two doses of MSC-derived extracellular vesicles had been administered to patients of group “A”. Blood urea, serum creatinine, urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used to assess kidney functions and TNF-α, TGF-β1 and IL-10 have been used to assess the amelioration of the inflammatory immune activity.ResultsParticipants in group A exhibited significant improvement of eGFR, serum creatinine level, blood urea and UACR. Patients of the treatment group “A” also exhibited significant increase in plasma levels of TGF-β1, and IL-10 and significant decrease in plasma levels of TNF-α. Participants of the control group B did not show significant improvement in any of the previously mentioned parameters at any time point of the study period. ConclusionAdministration of cell-free cord-blood mesenchymal stem cells derived extracellular vesicles (CF-CB-MSCs-EVs) is safe and can ameliorate the inflammatory immune reaction and improve the overall kidney function in grade III-IV CKD patients.

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

“…In total, we are aware of 41 patients which have been treated with MSC-EVs (74,77), none of which showed any side effect. In addition, we and others have applied MSC-EVs to an increasing amount of different animal models for various diseases.…”

“…A single centre study, randomized, placebo-controlled, phase II/III clinical pilot study, was performed with 40 patients in Cairo, Egypt (77). All patients, median age 24.65±0.75 years (range, 19-34 years), suffered from CDK for at least 6 months.…”

Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair

“…However, to date only one clinical trial investigated the safety and therapeutic efficacy of MSC-derived EVs in patients with kidney disease [79]. This single-center, randomized, placebo-controlled, phase II/III clinical pilot study recruited 40 patients with stage III-IV CKD (eGFR between 15-60mg/ml/min), who were randomized to receive either placebo or two doses (first intravenous and second intra-arterial) of MSC-derived EVs, one week apart.…”

“…Clinical improvement paralleled changes in plasma levels of several immune inflammatory markers, including TNF-α, TGF-β1, and IL-10. Although kidney biopsy specimens obtained 3 months after therapy did not show significant histologic changes, expression of Ki67 (a marker of regeneration) and the number of CD133 cells (possessing capabilities of clonal expansion and repair) were both upregulated in kidney samples [79]. These observations suggest that MSC-derived EVs are safe and can ameliorate the inflammatory immune reaction and improve the overall kidney function in patients with CKD.…”

Erratum to: Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases

“…Following the publication of our article [1], we would like to make some corrections to the text as detailed below:…”