Abstract

Impact of Combined Adipose-Derived Mesenchymal Stem Cell (ADMSC) and Low-Energy of Extracorporeal Shock Wave Therapy on Protecting Brain Death-Induced Remote Organ Damage in Rat

Author(s): Mel S Lee, Hung-Sheng Lin, Christopher Glenn Wallace, Jiunn-Jye Sheu, Pei-Hsun Sung, Kuan-Hung Chen, Sheng-Ying Chung, Pei-Lin Shao, Kun-Chen Lin, Ching-Jen Wang, Hon-Kan Yip, Fan-Yen Lee

ABSTRACT

Objective: This study tested the hypothesis that allogenic adipose-derived mesenchymal stem cell (ADMS) and extracorporeal shock wave (ECSW) therapy could attenuate brain death (BD)-induced remote cardiac organ damage in rat.

Methods: Adult-male SD rats (n=30) were equally divided into group 1 (sham control); group 2 (BD); group 3 [BD + ECSW (0.15 mJ/mm2/300 impulses applied to skull surface 3 h after BD induction)]; group 4 [BD + ADMSC (1.2 x 106 cell) by intravenous injection 3 h after BD induction]; and group 5 (BD-ECSW-ADMSC). Animals were sacrificed by 6 h after BD induction and the heart specimens harvested.

Results: ELISA analysis showed that the circulating level of inflammation (IL-6/MPO/TNF-α) was lowest in group 1, highest in group 2, significantly lower in groups 5 than in groups 3 and 4, and significantly lower in group 4 than in group 3 (all p<0.0001). Flow cytometry demonstrated that circulating inflammatory (Ly6G+) cells and circulating/splenic immune (CD3/CD4+/CD3/CD8+) exhibited an identical pattern whereas Treg+ cells expressed an opposite pattern of inflammatory biomarkers (all p<0.001). The protein expressions of inflammatory (IL-1s/MMP-9/TNF-α/NF-κB/), and apoptotic (cleaved/caspase-3/PARP/ mitochondrial Bax), oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited an identical pattern, whereas the protein expressions of mitochondrial integrity (mitochondrial cytochrome C) and anti-inflammatory (IL-4/IL-10) biomarkers exhibited an opposite pattern to inflammatory biomarkers among the five groups (all p<0.0001). The expressions of myocardial inflammatory (CD14+/CD68+) and immune (CD3+/CD4+) cells displayed an identical pattern of inflammatory biomarkers among the five groups (all p<0.0001).

Conclusion: ECSW-ADMSC therapy effectively protected the remote cardiac organ against BD-induced damage.