Proteomic Assessment of Hypoxia-Pre-Conditioned Human Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Demonstrates Promise in the Treatment of Cardiovascular Disease

被引:9
作者
Xu, Cynthia M. M. [1 ,2 ]
Karbasiafshar, Catherine [1 ]
Teixeira, Rayane Brinck [1 ,2 ]
Ahsan, Nagib [3 ,4 ]
Corssac, Giana Blume [5 ]
Sellke, Frank W. [1 ,2 ]
Abid, M. Ruhul [1 ,2 ]
机构
[1] Rhode Isl Hosp, Cardiovasc Res Ctr, Providence, RI 02903 USA
[2] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Div Cardiothorac Surg, Providence, RI 02903 USA
[3] Univ Oklahoma, Stephenson Life Sci Res Ctr, Mass Spectrometry Prote & Metabol Core Facil, Norman, OK 73019 USA
[4] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA
[5] Univ Fed Rio Grande do Sul, Basic Hlth Sci Inst, Cardiovasc Physiol Lab, Porto Alegre, RS, Brazil
关键词
human bone marrow mesenchymal stem cell-derived extracellular vesicles; starvation; hypoxia; pre-conditioning; cardiovascular disease; EXOSOMES; METABOLISM; THERAPY;
D O I
10.3390/ijms24021674
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human bone marrow mesenchymal stem cell derived-extracellular vesicles (HBMSC-EV) are known for their regenerative and anti-inflammatory effects in animal models of myocardial ischemia. However, it is not known whether the efficacy of the EVs can be modulated by pre-conditioning of HBMSC by exposing them to either starvation or hypoxia prior to EV collection. HBMSC-EVs were isolated following normoxia starvation (NS), normoxia non-starvation (NNS), hypoxia starvation (HS), or hypoxia non-starvation (HNS) pre-conditioning. The HBMSC-EVs were characterized by nanoparticle tracking analysis, electron microscopy, Western blot, and proteomic analysis. Comparative proteomic profiling revealed that starvation pre-conditioning led to a smaller variety of proteins expressed, with the associated lesser effect of normoxia versus hypoxia pre-conditioning. In the absence of starvation, normoxia and hypoxia pre-conditioning led to disparate HBMSC-EV proteomic profiles. HNS HBMSC-EV was found to have the greatest variety of proteins overall, with 74 unique proteins, the greatest number of redox proteins, and pathway analysis suggestive of improved angiogenic properties. Future HBMSC-EV studies in the treatment of cardiovascular disease may achieve the most therapeutic benefits from hypoxia non-starved pre-conditioned HBMSC. This study was limited by the lack of functional and animal models of cardiovascular disease and transcriptomic studies.
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页数:12
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