Treatment With Human Wharton's Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction

Abstract

Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate.

Concise Review: Mesenchymal Stromal Cell-Based Approaches for the Treatment of Acute Respiratory Distress and Sepsis Syndromes

“…However, recent studies have also assessed the feasibility of utilizing MSC isolated from alternative sources whilst others are examining the therapeutic efficacy of MSC‐derived vesicles. In a recent publication, Cóndor et al analyzed the efficacy of MSCs derived from human Wharton's Jelly (WJ‐MSCs) in a rat sepsis model. In animals receiving 1 × 10 6 WJ‐MSC 6 hours after CLP, 5‐day survival was significantly increased (87.5% vs. 55.6% in CLP only) and both liver and kidney function were improved.…”

“…In vivo models of sepsis and ALI/ARDS have shown MSCs treatment to improve survival and to positively influence a number of [56], [57], [63], [64], [67], [70], [73]. Gupta et al [49] found that in mice, intrapulmonary administration of BMSC 4 hours after induction of ALI by E. coli endotoxin resulted in improved survival, reduced excess lung water and improved lung histology, resulting in a decrease of bronchoalveolar lavage (BAL) TNF-a and MIP-2 and an increase of IL-10 levels within BAL and plasma samples.…”

“…Interestingly, the authors reported no difference on day 3 survival amongst untreated CLP animals (89%) and those treated with either hBMSC (82%) or mBMSC (96%). The role of MSC in modulating cytokine levels in sepsis syndrome models is undoubtedly complex; concerning IL-10, conflicting results have shown MSCs to both positively [50,56,57,63,64,67,70,73] as well as negatively [46,54] influence levels, or alternatively have no effect [59,60]. There are similar inconsistencies in relation to IFN-g levels, with groups describing a reduction [50,57,73], an increase [70] or no effect [51,67].…”

Current Status of Stem Cell Therapy for Sepsis and Acute Respiratory Distress Syndrome

“…TSG-6 has a potent anti-inflammatory effect acting in macrophages and polarizing them from a pro-to an anti-inflammatory phenotype while reducing the secretion of inflammatory chemokines by these cells. IGF-1 has been described as an anti-apoptotic compound, and during sepsis and ARDS, less apoptosis of the endothelium and epithelium cells reduces the damage and the associated inflammation [62,63].…”

A Preview of Selected Articles

“…In the first of our Featured Articles this month published in STEM CELLS , Weiss et al employ mouse models of allogeneic heart transplantation and sepsis to highlight the importance of tailoring MSC‐based treatments to the disease as opposed to utilizing MSCs as a one‐size‐fits‐all therapeutic solution . In a Related Article published in STEM CELLS Translational Medicine , Cóndor et al demonstrated that human Wharton's jelly‐derived MSCs adequately protected against renal, hepatic, and endothelial dysfunction in a rat model of sepsis …”