Therapeutic effects of adipose-derived mesenchymal stem cells against brain death-induced remote organ damage and post-heart transplant acute rejection

Abstract

We tested the hypothesis that allogenic adipose-derived mesenchymal stem cells (ADMSCs) alleviated brain death (BD)-induced remote organ damage and events of post heart-transplant acute rejection. To determine the impact of BD on remote organ damage, adult-male F344 rats (n=24) were categorized sham-control (SC), BD and BDMSC (allogenic ADMSC/1.2 × 106 cells/derived from F344 by intravenous transfusion 3 h after BD procedure). To determine the protective effect of allogenic ADMSCs, animals (n=8/each group in F344/Lewis) were categorized into groups BD-T(F344 heart transplanted into Lewis by 6h after BD), BD-TMSC(D1/3) (BD induction for 6h then heart transplantation, and allogenic ADMSCs transfusion at days 1 and 5 after heart transplantation), BD-TMSC(3h) (BD + ADMSC/1.2 × 106 cells at 3h and heart transplantation at 6h after BD) and BD-TMSC(3h, D1/3) [BD + ADMSC/1.2 × 106 cells at 3h and heart transplantation at 6h after BD, then ADMSC therapy by days 1/3]. At day 5 post procedure, liver, kidney and heart specimens showed higher molecular-cellular levels of inflammation, immune reaction, apoptosis and fibrosis in BD than in SC that were reversed in BDMSC (all P < 0.0001). These molecular-cellular expressions and circulating/splenic levels of innate/adoptive immune cells were higher in BD-T, lowest in BD-TMSC(3h, D1/3) and higher BD-TMSC(3h) in than BD-TMSC(D1/3), whereas heart function showed an opposite pattern among the four groups (all P < 0.001). In conclusion, ADMSCs suppressed BD-caused remote organ damage and heart-transplant rejection.

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

“…One important finding in the present study was that intravenous administration of allogenic AMDSC effectively ameliorated BD-caused remote cardiac organ damage. Interestingly, our recent study demonstrated that allogenic ADMSC therapy significantly reduced the incidence of BDinduced post heart-transplanted rejection [37]. Our current findings therefore corroborate those of our recent study [37].…”

“…Interestingly, our recent study demonstrated that allogenic ADMSC therapy significantly reduced the incidence of BDinduced post heart-transplanted rejection [37]. Our current findings therefore corroborate those of our recent study [37]. Another important finding was that ECSW therapy was comparably as effective as ADMSC for alleviating BDcaused remote cardiac damage.…”

“…An essential finding in the present study was that not only the localized (i.e., within the heart tissue specimen) but also the systemic molecular-cellular inflammatory and immune perturbations have been clearly identified in the rat after BD procedure. Our findings, in addition to strengthening the findings of previous studies [19,21,[27][28][29][35][36][37], could explain why the 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 heart organ was damaged after BD procedure in rat. Of importance, ECSW or ADMSC therapy significantly, and combined ECSW-ADMSC more significantly, ameliorated the innate (i.e., inflammation) and adaptive (immune) reactions in SD rat in setting of BD.…”

“…Growing data have shown that BD commonly causes remote organ damage, particularly of heart Research Jinsong Wu [17,37]. Although the underlying mechanism of BD-caused remote organ damage has been extensively investigated [11][12][13][14][15][16][17]37], effective treatments have seldom been reported [37].…”

“…Abundant data has delineated that ischemic stroke (IS) and BD commonly elicit inflammatory reactions and upregulate the immune response [5][6][7][8][9][10][11][12][13][14][15][16][17]36]. Links between an increase in inflammatory/immune reaction and tissue/organ damage has been recognized by several previous studies [19,21,[27][28][29][35][36][37]. An essential finding in the present study was that not only the localized (i.e., within the heart tissue specimen) but also the systemic molecular-cellular inflammatory and immune perturbations have been clearly identified in the rat after BD procedure.…”