Abstract:
:Mesenchymal stem cell (MSC) transplantation has been widely applied as a potential therapeutic for multiple diseases. However, the underlying therapeutic mechanisms are not fully understood, especially the paradox between the low survival rate of transplanted cells and the beneficial therapeutic effects generated by these cells. Herein, in a myocardial infarction (MI) model, we found that transplanted MSCs released apoptotic bodies (ABs) to enhance angiogenesis and improve cardiac functional reclovery via regulating macroautophagy/autophagy in the recipient endothelial cells (ECs). Mechanistically, after local transplantation, MSCs underwent extensive apoptosis in the short term and released ABs, which were engulfed by the recipient ECs. Then, in the ECs, ABs activated lysosome functions and promoted the expression of TFEB (transcription factor EB), which is a master gene in lysosomal biogenesis and autophagy. Finally, the increase in TFEB enhanced autophagy-related gene expression in ECs and promoted angiogenesis and cardiac functional recovery after MI. Collectively, we found that apoptotic donor MSCs promote angiogenesis via regulating autophagy in the recipient ECs, unveiling the role of donor cell apoptosis in the therapeutic effects generated by cell transplantation. Abbreviations: 3-MA: 3-methyladenine; ABs: apoptotic bodies; BECN1: beclin 1; CASP3: caspase 3; CQ: chloroquine; ECs: endothelial cells; EVs: extracellular vesicles; LAMP1: lysosomal-associated membrane protein 1; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MI: myocardial infarction; MSC: mesenchymal stem cell; NO: nitric oxide; TFEB: transcription factor EB; TUNEL: TdT-mediated dUTP Nick-End Labeling.
journal_name
Autophagyjournal_title
Autophagyauthors
Liu H,Liu S,Qiu X,Yang X,Bao L,Pu F,Liu X,Li C,Xuan K,Zhou J,Deng Z,Liu S,Jin Ydoi
10.1080/15548627.2020.1717128subject
Has Abstractpub_date
2020-12-01 00:00:00pages
2140-2155issue
12eissn
1554-8627issn
1554-8635journal_volume
16pub_type
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