Review
Copyright ©The Author(s) 2015.
World J Stem Cells. Mar 26, 2015; 7(2): 368-379
Published online Mar 26, 2015. doi: 10.4252/wjsc.v7.i2.368
Table 1 Efficacy preclinical studies on experimental models of sepsis using mesenchymal stem cells, mesenchymal stem cell-conditioned medium or mesenchymal stem cell-derived macrophages
Animal modelMSC typeRoute/timeDoseNumber of dosesTherapeutic effects
MoARef.
SurvivalCytokinesInflammatory infiltrationOrgan injuryBacterial load
LPS, mousehASCs (xeno)I.P/after 0.5 h or I.P/after 0.5 h3 × 105 1061 1Improved ImprovedReduced pro-inflammatory cytokines in serum, liver, lung and intestine Increased anti-inflammatory cytokine (IL10) in liver, lung and intestineReduced lymphocyte, neutrophil and macrophage infiltration in peritoneum, liver, lung and intestineNDNDNDGonzalez-Rey et al[52]
LPS, mousehBM-MSCs (xeno) normal/senescentI.P/after 0.5 h1061Improved only by normal cellsReduced pro-inflammatory cytokines in serum and lungs (normal cells) Reduced anti-inflammatory cytokine (IL10) in serum (normal cells)NDNDNDNDSepúlveda et al[67]
LPS, mousehASC/BM-MSC-CMI.P/at 0 h1 mL CM (from 2× 106 cells per milliliter)1Improved only by hBM-MSC CMNDReduced neutrophil infiltration in kidney (hBM-MSC CM)Improved kidney, liver and lung damage (hBM-MSC CM)NDNDElman et al[65]
LPS, rathASCs (xeno)I.V/after 0.5 h2 × 1061NDReduced pro-inflammatory cytokines in lung No effect on anti-inflammatory cytokine (IL10)NDImproved kidney, liver and lung damageNDNDShin et al[75]
LPS, rathBM-MSCs (xeno)I.M/at 0 h2 × 1061NDNDNDImproved kidney, liver and lung damageNDNDYagi et al[73]
LPS, rathBM-MSCs (xeno)I.M/at 0 h2 × 1061NDReduced pro-inflammatory cytokines in serumReduced neutrophil and macrophage infiltration in kidney, liver and lungNDNDMSC release of sTNFR1Yagi et al[76]
LPS, ratmBM-MSCs (xeno)I.P/after 1 h2 × 1061NDReduced pro-inflammatory cytokines in serum and myocardium Increased anti-inflammatory cytokine (IL10) in serum but not in myocardiumNDImproved myocardial damage Cells from female donors showed higher effectNDHigher expression of anti-apoptotic proteins in myocardiumManukyan et al[71]
LPS, ratmBM-MSCs (xeno)I.P/after 1 h2 × 1061NDReduced pro-inflammatory cytokines in serum and myocardium Increased anti-inflammatory cytokine (IL10) in serum but not in myocardiumNDImproved myocardial damageNDNDWeil et al[72]
LPS, ratrBM-MSCs (auto)I.V/after 1 h2.5 × 1061NDReduced pro-inflammatory cytokines in serum and myocardium Increased anti-inflammatory cytokine (IL10) in serum but not in myocardiumNDImproved myocardial damageNDNDWeil et al[74]
CLP, mousehASCs (xeno) mASCs (auto/allo)I.P/after 4 h1061ImprovedReduced pro-inflammatory cytokines in serum, liver, lung and intestine Increased anti-inflammatory cytokine (IL10) in liver, lung and intestineReduced lymphocyte, neutrophil and macrophage infiltration in peritoneum, liver, lung and intestineNDNDNDGonzalez-Rey et al[52]
CLP, mousemBM-MSCs (auto/allo)I.V/24 h prior or I.V/after 1 h106 1061 1Improved ImprovedReduced pro-inflammatory cytokines in serum Increased anti.inflammatory cytokine (IL10) in serumReduced neutrophil infiltration in peritoneum, liver and kidneyImproved kidney, liver, pancreatic and spleen damage and vascular permeabilityReduced bacterial counts in bloodAnti-inflammatory Mph (IL10) induced by MSCs through PGE2Németh et al[61]
CLP, mousemBM-MSCs (auto)I.V/after 6 h2.5 × 1051ImprovedReduced pro-inflammatory cytokines in serum and BAL No effect on anti.inflammatory cytokine (IL10) in serum and BALReduced neutrophil infiltration in peritoneum, liver and kidneyImproved kidney and lung damage. No effect on liver and pancreatic damageReduced bacterial counts in spleenIncreased phagocytic activity of macrophages and neutrophilsMei et al[62]
CLP, mousemBM-MSCs (auto)I.V/after 2 h and I.V/after 24 h and I.V/after 48 h5 × 105 2.5 × 105 2.5 × 105 total: 1063ImprovedNDReduced neutrophil infiltration in bowelImproved bowel, kidney, liver and spleen damageReduced bacterial counts in peritoneum and bloodIncreased phagocytic activity of neutrophilsHall et al[64]
CLP, mousemBM-MSCs (auto)I.V/after 3 h1061ImprovedReduced pro-inflammatory cytokines in serum Increased anti-inflammatory cytokine (IL10) in serumReduced neutrophil infiltration in kidneyImproved kidney damageReduced bacterial counts in bloodNDLuo et al[66]
CLP, mouseASC-derived mouse MphI.P/after 4 h or I.P/after 6 h or I.P/after 12 h or I.P/after 24 h106 106 106 1061 1 1 1Improved Improved Improved No effectReduced pro-inflammatory cytokines in serum (only treatment at 4 h tested)Reduced lymphocyte, neutrophil and macrophage infiltration in peritoneum, lung, liver and intestine (only treatment at 4 h tested)NDNDIL10 secreted by MphAnderson et al[77]
CLP, mousehUC-MSCs (xeno) wt/Poly I:C preactivatedI.V/after 1 h1061Improved Better preactivatedReduced pro-inflammatory cytokines in plasma Better preactivatedReduced inflammatory infiltration in kidney, liver and lungImproved kidney, liver and pancreatic damage Better preactivatedReduced bacterial counts in peritoneum and blood Better preactivatedPoly I:C inhibition of MiR-143 expression by MSCsZhao et al[68]
CLP, ratrASCs (auto) living/apoptoticI.P/after 0.5 h and I.P/after 6 h and I.P/after 18 h1.2 × 106 1.2 × 106 1.2 × 106 total: 3.6 ×1063Higher mortality by living cells Improved by apoptotic cellsReduced TNFα ( apoptotic rASC treated rats)NDImproved kidney, liver, lung and myocardial damage (apoptotic rASCs)NDNDChang et al[69]
E.coli pneumonia, mousehBM-MSCs (xeno)I.T/after 4 h1061NDReduced pro-inflammatory cytokines in bronchoalveolar liquid (BAL)Reduced neutrophil infiltration in BALImproved lung epithelial and endothelial permeabilityReduced bacterial counts in BALMSC release of the antimicrobial peptide LL-37Krasnodems- kaya et al[70]
P. aeruginosa peritonitis, mousehBM-MSCs (xeno)I.V/after 1 h1061ImprovedNo changes in serum or peritoneal fluid levels of pro or anti-inflammatory mediatorsNDNDReduced bacterial counts in peripheral blood, peritoneal fluid, lung, and spleenIncreased phagocytic activity of macrophages Generation of anti-inflammatory macrophages in spleenKrasnodems- kaya et al[63]