Miss CHEN WEI1, Ms ADRIANA KNEZIC1, Mr BRADLEY BROUGHTON1, Ms SHARON RICARDO1, Mr CHRISHAN SAMUEL1
1Monash University, Clayton, Australia
Biography:
Chen is a second year PhD candidate in the Department of Pharmacology, Monash University (Fibrosis Laboratory), working under the supervision of Professor Chrishan Samuel and Professor Sharon Ricardo. Her PhD thesis aims to examine the therapeutic effects of a combination stem cell-based therapy, incorporating human bone marrow mesenchymal stem cells (BM-MSCs) and the anti-fibrotic hormone, relaxin, in hypertensive marmosets (non-human primates)
Aim:
To compare the therapeutic effects of human bone marrow-derived mesenchymal stem cells (BM-MSCs) and the anti-fibrotic hormone, relaxin, via separate modes of delivery or a single injection of genetically-engineered relaxin-producing BM-MSCs (RLX-BM-MSCs) in hypertensive marmosets.
Background:
Hypertension is a leading risk factor for chronic kidney disease and cardiovascular disease, yet current treatments mainly lower blood pressure, but do not reverse established fibrosis-induced organ damage. We recently developed RLX-BM-MSCs by lentiviral transfection to express relaxin and GFP. In hypertensive mice, combining the immunomodulatory and anti-hypertensive effects of BM-MSCs with relaxin significantly reduced renal and cardiac fibrosis beyond BM-MSCs alone. Here, we assessed the efficacy of engineered RLX-BM-MSCs in hypertensive marmosets as a step towards clinical translation.
Methods:
7-10 year-old male marmosets with blood pressures of 150-160mmHg (n=12) were treated with either an ACE inhibitor (perindopril; 2mg/kg/day) alone (n=4); perindopril, minipump-infused relaxin (0.5mg/kg/day) and i.v-administered BM-MSCs (2.5x10E6 x 2, 7-days apart; n=4); or perindopril and i.v-administered RLX-BM-MSCs (2.5x10E6 x 2, 7-days apart; n=4). Blood pressure was measured weekly from baseline (prior to treatment) to 21 days post-treatment. At day 21 post-treatment, the kidney and heart of these marmosets were collected for histological and biochemical assessment.
Results:
Marmosets treated with either of the combined cell-based therapies had significantly reduced systolic blood pressures (~45-50mmHg; compared to the perindopril-induced reduction of ~35mmgHg); and significantly reduced kidney and left ventricular inflammation, fibrosis, glomerulosclerosis, cardiomyocyte hypertrophy and vascular rarefaction (all by ~20-50%) compared to perindopril alone, at day 21 post-treatment treatment.
Conclusions:
These findings demonstrated that RLX-BM-MSCs maintained the therapeutic effects of the combined cell-based treatment administered separately, and may represent a novel treatment option for hypertensive kidney and cardiovascular diseases.
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