Details

Autor(en) / Beteiligte

• Aliotta, Jason M.
• Pereira, Mandy
• Wen, Sicheng
• Dooner, Mark S.
• Del Tatto, Michael
• Papa, Elaine
• Cheng, Yan
• Goldberg, Laura
• Ventetuolo, Corey E.
• Liang, Olin
• Klinger, James R.
• Quesenberry, Peter J.

Titel

Bone Marrow Endothelial Progenitor Cells Are the Cellular Mediators of Pulmonary Hypertension in the Murine Monocrotaline Injury Model

Ist Teil von

• Stem cells translational medicine, 2017-07, Vol.6 (7), p.1595-1606

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• The role of bone marrow (BM) cells in modulating pulmonary hypertensive responses is not well understood. Determine if BM‐derived endothelial progenitor cells (EPCs) induce pulmonary hypertension (PH) and if this is attenuated by mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs). Three BM populations were studied: (a) BM from vehicle and monocrotaline (MCT)‐treated mice (PH induction), (b) BM from vehicle‐, MCT‐treated mice that received MSC‐EV infusion after vehicle, MCT treatment (PH reversal, in vivo), (c) BM from vehicle‐, MCT‐treated mice cultured with MSC‐EVs (PH reversal, in vitro). BM was separated into EPCs (sca‐1+/c‐kit+/VEGFR2+) and non‐EPCs (sca‐1‐/c‐kit‐/VEGFR2‐) and transplanted into healthy mice. Right ventricular (RV) hypertrophy was assessed by RV‐to‐left ventricle+septum (RV/LV+S) ratio and pulmonary vascular remodeling by blood vessel wall thickness‐to‐diameter (WT/D) ratio. EPCs but not non‐EPCs from mice with MCT‐induced PH (MCT‐PH) increased RV/LV+S, WT/D ratios in healthy mice (PH induction). EPCs from MCT‐PH mice treated with MSC‐EVs did not increase RV/LV+S, WT/D ratios in healthy mice (PH reversal, in vivo). Similarly, EPCs from MCT‐PH mice treated with MSC‐EVs pre‐transplantation did not increase RV/LV+S, WT/D ratios in healthy mice (PH reversal, in vitro). MSC‐EV infusion reversed increases in BM‐EPCs and increased lung tissue expression of EPC genes and their receptors/ligands in MCT‐PH mice. These findings suggest that the pulmonary hypertensive effects of BM are mediated by EPCs and those MSC‐EVs attenuate these effects. These findings provide new insights into the pathogenesis of PH and offer a potential target for development of novel PH therapies. Stem Cells Translational Medicine 2017;6:1595–1606 In pulmonary hypertension (PH), the lung releases extracellular vesicles (EVs) that alter bone marrow‐derived endothelial progenitor cells, converting them into pathologic progenitors that traffic to the lung and induce pulmonary vascular remodeling. The pathologic properties of these progenitor cells can be reversed by mesenchymal stem cell‐derived EVs, preventing them from inducing PH in healthy mice.