Mesenchymal stem cells (MSCs) have been reported to improve
survival of cardiomyocytes (CMCs) and overall regeneration of
cardiac tissue. Despite promising preclinical results, interactions
of MSCs and CMCs, both direct and indirect, remain unclear. In
this study, porcine bone marrow MSCs and freshly isolated
porcine primary adult CMCs were used for non-contact co-culture
experiments. Morphology, viability and functional parameters of
CMCs were measured over time and compared between CMCs
cultured alone and CMCs co-cultured with MSCs. In non-contact
co-culture, MSCs improved survival of CMCs. CMCs co-cultured
with MSCs maintained CMCs morphology and viability in
significantly higher percentage than CMCs cultured alone. In
viable CMCs, mitochondrial respiration was preserved in both
CMCs cultured alone and in CMCs co-cultured with MSCs.
Comparison of cellular contractility and calcium handling,
measured in single CMCs, revealed no significant differences
between viable CMCs from co-culture and CMCs cultured alone.
In conclusion, non-contact co-culture of porcine MSCs and CMCs
improved survival of CMCs with a sufficient preservation of
functional and mitochondrial parameters.
Renal sympathetic hyperactivity is critically involved in hypertension pathophysiology; renal denervation (RDN) presents a novel strategy for treatment of resistant hypertension cases. This study assessed effects of two RDN systems to detect acute intravascular, vascular and peri-vascular changes in the renal artery, and renal nerve alterations, in the sheep. The procedures using a single-point or multi-point ablation catheters, Symplicity FlexTM, Medtronic versus EnligHTNTM, St. Jude Medical were compared; the intact contralateral kidneys served as controls. Histopathological and immunohistochemical assessments were performed 48 h after RDN procedures; the kidney and suprarenal gland morphology was also evaluated. Special staining methods were applied for histologic analysis, to adequately score the injury of renal artery and adjacent renal nerves. These were more pronounced in the animals treated with the multi-point compared with the single-point catheter. However, neither RDN procedure led to complete renal nerve ablation. Forty-eight hours after the procedure no significant changes in plasma and renal tissue catecholamines were detected. The morphologic changes elicited by application of both RDN systems appeared to be dependent on individual anatomical variability of renal nerves in the sheep. Similar variability in humans may limit the therapeutic effectiveness of RDN procedures used in patients with resistant hypertension., M. Táborský, D. Richter, Z. Tonar, T. Kubíková, A. Herman, J. Peregrin, L. Červenková, Z. Husková, L. Kopkan., and Obsahuje bibliografii
This study evaluated the subacute morphologic alterations in renal artery wall and renal nerves in response to catheter-based renal denervation (RDN) in sheep and also compared the efficiency of single-point and multiple-point ablation catheters. Effect of each ablation catheter approved for the clinical use (Symplicity FlexTM, Medtronic, Inc., or EnligHTNTM, St. Jude Medical, INC.) was compared to intact contralateral renal artery in 12 sheep by histopathology and immunohistochemistry evaluation after a 10-day period post-RDN procedure. The safety was verified by extensive evaluation of kidney morphology. Vascular wall lesions and nerve injuries were more pronounced in those animals treated with multi-point EnligHTN catheter when compared with animals treated with single-point Symplicity Flex catheter. However, neither RDN procedure led to complete renal nerve ablation. Both systems, tested in the present study, provided only incomplete renal nerve ablation in sheep. Moreover, no appreciable progression of the nerve disintegration in subacute phase post-RDN procedure was observed. This study further supports the notion that the effectiveness remains fully dependent on anatomical inter-individual variability of the sympathetic nerve plexus accompanying the renal artery. Therefore, new systems providing deeper penetrance to targeted perivascular structure would be more efficient.