Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are known to exert immunomodulatory and pro-reparative effects inĀ vivo. This makes hBM-MSCs an enticing therapeutic candidate for inflamm Show more
Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are known to exert immunomodulatory and pro-reparative effects inĀ vivo. This makes hBM-MSCs an enticing therapeutic candidate for inflammatory diseases, such as acute respiratory distress syndrome (ARDS). The ARDS microenvironment is complex and contains an abundance of free fatty acids (FFAs), which are known to differentially impact MSC functionality. PPARĪ²/Ī“ is a ubiquitously expressed nuclear receptor that is activated in response to FFA-binding. PPARĪ²/Ī“ has been shown to impact the therapeutic efficacy of mouse MSCs. This study sought to investigate the impact of PPARĪ²/Ī“-modulation on human MSC functionality inĀ vitro and inĀ vivo. hBM-MSCs were exposed to a synthetic PPARĪ²/Ī“ agonist/antagonist in the presence or absence of ARDS patient serum and the immunomodulatory and pro-reparative capacity of the MSC secretome was investigated using inĀ vitro assays and a pre-clinical model of LPS-induced acute lung inflammation (ALI). Our results highlighted enhanced pro-reparative capacity of PPARĪ²/Ī“-agonized hBM-MSCs secretome in CALU-3 lung epithelial cells, mediated by MSC derived angiopoietin-like 4 (ANGPTL4). PPARĪ²/Ī“-induced ANGPTL4-high MSC secretome facilitated enhanced endothelial barrier integrity in the lungs of ALI mice. Therapeutic effects of PPARĪ²/Ī“-agonized hBM-MSCs secretome were further enhanced by licensing MSCs with human ARDS patient serum. ARDS-licensed PPARĪ²/Ī“-induced ANGPTL4-high MSC secretome had reduced clinical score and weight loss. The role ANGPL4 in these protective effects was confirmed using an anti-ANGPTL4 antibody. These findings conclude that the MSC secretome therapeutic effects can be enhanced both inĀ vitro and inĀ vivo through licensing strategies that upregulate the angiogenic factor ANGPTL4. Show less
Molecular research for genetic variants underlying body weight (BW) provides crucial information for this important selected trait when developing productive poultry breeds, lines and crosses. We sear Show more
Molecular research for genetic variants underlying body weight (BW) provides crucial information for this important selected trait when developing productive poultry breeds, lines and crosses. We searched for molecular markers-single nucleotide polymorphisms (SNPs)-and candidate genes associated with this trait in 240 F Show less