Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension.
Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called "priming" factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 μM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK(p42/44) and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients.
['Lim|Jisun|J|', 'Kim|YongHwan|Y|', 'Heo|Jinbeom|J|', 'Kim|Kang-Hyun|KH|', 'Lee|Seungun|S|', 'Lee|Sei Won|SW|', 'Kim|Kyunggon|K|', 'Kim|In-Gyu|IG|', 'Shin|Dong-Myung|DM|']
D000818:Animals D000893:Anti-Inflammatory Agents D002465:Cell Movement D049109:Cell Proliferation D002518:Ceramides D006801:Humans D006976:Hypertension, Pulmonary D017380:Hypertrophy, Right Ventricular D020935:MAP Kinase Signaling System D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D016686:Monocrotaline D051057:Proto-Oncogene Proteins c-akt D011651:Pulmonary Artery D051381:Rats D011917:Rats, Inbred Lew D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D013234:Stem Cells
Priming Ceramide-1 phosphate Pulmonary artery hypertension Mesenchymal stem cell