TY - JOUR
T1 - Antimicrobial activity of mesenchymal stem cells
T2 - current status and new perspectives of antimicrobial peptide-based therapies
AU - Alcayaga-Miranda, Francisca
AU - Cuenca, Jimena
AU - Khoury, Maroun
N1 - Funding Information:
The authors specially thank Dr. Fernando Figueroa and Dr. Francisco Espinoza (Medicine Faculty, Universidad de los Andes, Santiago, Chile) for their helpful scientific and clinical discussions. This work was funded by Cells for Cells (Santiago, Chile), Consorcio Regenero (Santiago, Chile) and by the Chilean National Commission for Scientific and Technological Investigation (CONICYT), FONDEF IDeA Instrument, grant number IT16I10084.
Publisher Copyright:
© 2017 Alcayaga-Miranda, Cuenca and Khoury.
PY - 2017/3/30
Y1 - 2017/3/30
N2 - While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in preclinical models of sepsis, acute respiratory distress syndrome, and cystic fibrosis-related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect, are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug-resistant strains.
AB - While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in preclinical models of sepsis, acute respiratory distress syndrome, and cystic fibrosis-related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect, are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug-resistant strains.
KW - AMPs
KW - Antibacterial property
KW - Antimicrobial effect
KW - Mesenchymal stem cells
KW - Mesenchymal stromal cells
UR - http://www.scopus.com/inward/record.url?scp=85017163102&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.00339
DO - 10.3389/fimmu.2017.00339
M3 - Review article
AN - SCOPUS:85017163102
SN - 1664-3224
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - MAR
M1 - 339
ER -