Extracorporeal shock wave enhanced exogenous mitochondria into adipose-derived mesenchymal stem cells and further preserved heart function in rat dilated cardiomyopathy

Pei Hsun Sung, Mel S. Lee, Han Tan Chai, John Y. Chiang, Yi Chen Li, Yi Ching Chu, Chi Ruei Huang, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

1 Scopus citations

Abstract

This study tested whether extracorporeal shock wave (ECSW) supported-exogenous mitochondria (Mito) into adipose-derived mesenchymal stem cells (ADMSCs) would preserve left-ventricular-ejection-fraction (LVEF) in doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) rat. Adult-male-SD rats were equally categorized into group 1 (sham-control), group 2 (DCM), group 3 (DCM + ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction), group 4 (DCM + ECSW/1.5 mJ/mm2 /100 shots-assisted mito delivery (500 µg) into ADMSCs/1.2 × 106 cells, then implanted into LV myocardium day 14 after DCM induction) and group 5 (DCM + ECSW-assisted mito delivery into ADMSCs/1.2 × 106 cells, then implanted into LV, followed by ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction) and euthanized by day 49. Microscopic findings showed mitochondria were abundantly enhanced by ECSW into H9C2 cells. The q-PCR showed a significant increase in relative number of mitDNA in mitochondrial-transferred H9C2 cells than in control group (p < 0.01). The angiogenesis/angiogenesis factors (VEGF/SDF-1α/IG-F1) in HUVECs were significantly progressively increased by a stepwise-increased amount of ECSW energy (0.1/0.25/0.35 mJ/mm2 ) (all p < 0.001). The 49-day LVEF was highest in group 1 and significantly progressively increased from groups 2 to 5 (all p < 0.0001). Cardiomyocyte size/fibrosis exhibited an opposite pattern of LVEF, whereas cellular/protein levels of angiogenesis factors (VEGF/SDF-1α) in myocardium were significantly progressively increased from groups 1 to 5 (all p < 0.0001). The protein expressions of apoptotic/mitochondrial (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax/cytosolic-cytochrome-C), fibrotic (p-Smad3/TGF-ß), oxidative-stress (NOX-1/NOX-2) and pressure-overload/heart failure (BNP/ß-MHC) biomarkers exhibited an opposite pattern of LVEF among the five groups (all p < 0.0001). ECSW-assisted mitochondrial-delivery into ADMSCs plus ECSW offered an additional benefit for preserving LVEF in DCM rat.

Original languageEnglish
Article number1362
JournalBiomedicines
Volume9
Issue number10
DOIs
StatePublished - 10 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Angiogenesis
  • Dilated cardiomyopathy
  • Exogenous mitochondria delivery
  • Extracorporeal shock wave
  • Left ventricular ejection fraction

Fingerprint

Dive into the research topics of 'Extracorporeal shock wave enhanced exogenous mitochondria into adipose-derived mesenchymal stem cells and further preserved heart function in rat dilated cardiomyopathy'. Together they form a unique fingerprint.

Cite this