Biology subjects

del Nido, P. J.

Publications and source records attributed to del Nido, P. J..

3 recordsLinked to original sources

bioRxiv2026

The Role of Secondary Chordae Tendineae in Mitral Valve Mechanics: A Benchtop Study

PurposeSecondary chordae tendineae (CT) are frequently disregarded during mitral valve (MV) repair. However, their contribution to MV biomechanics remains poorly understood. We hypothesized that secondary CT play an important role in maintaining leaflet geometry during valve closure. MethodsEleven explanted porcine MVs were micro-CT scanned in a systolic configuration under three conditions: (1) physiological baseline with all secondary CT intact, (2) transection of the A2 strut CT, and (3) transection of all secondary CT. Billowing height (BH), coaptation height (CH) along the parasternal long-axis view, and coaptation area (CA) were quantified and compared between conditions. An increase in BH[≥] 2 mm from baseline was defined as pathological. ResultsTransection of the A2 strut CT increased BH by 3.1 mm, exceeding the pathological billowing threshold by 1.1 mm (padj = 0.003). CH decreased by 0.6 mm (padj = 0.003), whereas CA showed no significant change compared with baseline. Subsequent transection of all secondary CT further increased BH to 4.8 mm relative to baseline, corresponding to 2.8 mm above the billowing threshold (padj = 0.003). CH did not differ significantly, while CA decreased by 0.35 cm2 compared with baseline (padj = 0.029). All values represent medians. ConclusionSecondary CT play a critical role in stabilizing MV leaflet geometry. Their transection resulted in increased leaflet billowing and reduced coaptation metrics associated with unfavorable MV repair outcomes. Preservation or reconstruction of secondary CT may therefore be an important consideration in MV repair strategies.

bioengineering↗

bioRxiv2022

Enhanced intramyocardial vascular cell delivery promotes post-myocardial infarction healing by polarizing pro-regenerative neutrophils

The success of vascular progenitor cell transplantation to treat myocardial infarction (MI) is primarily limited by the low engraftment of delivered cells due to a washout effect during myocardium contraction. A clinically applicable biomaterial to improve cell retention is arguably needed to enable optimization of intramyocardial cell delivery. Here, we developed a novel therapeutic cell delivery method for MI treatment based on a photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. A combination of human vascular progenitor cells (endothelial progenitors and mesenchymal stem cells) with the capacity to form functional vasculatures after transplantation, were injected with a rapid in-situ photopolymerization approach into the infarcted zone of mouse hearts. Our approach significantly improved acute cell retention and achieved a long-term beneficial post-MI cardiac healing, including stabilizing cardiac functions, preserving viable myocardium, and preventing cardiac fibrosis. Furthermore, the engrafted vascular cells polarized recruited bone marrow-derived neutrophils toward a non-inflammatory phenotype via TGF{beta} signaling, establishing a pro-regenerative microenvironment. Depletion of neutrophils canceled the therapeutic benefits produced by cell delivery in the ischemic hearts, indicating that the non-inflammatory, pro-regenerative neutrophils were indispensable mediators of cardiac remodeling. In summary, our novel GelMA hydrogel-based intramyocardial vascular cell delivery approach has the potential to improve the treatment of acute MI.

bioengineering↗

bioRxiv2017

Transit and integration of extracellular mitochondria in human heart cells

Tissue ischemia adversely affects the function of mitochondria, which results in impairment of oxidative phosphorylation and compromised recovery of the affected organ. The impact of ischemia on mitochondrial function has been most extensively studied in the heart because of the morbidity and mortality associated with injury to this organ. Because conventional methods to preserve cell viability and function following an ischemic injury are limited in their efficacy, we developed a unique approach to protect the heart by transplanting respiration-competent mitochondria isolated from a non-ischemic tissue to the ischemic region. Our experiments in animals have shown that transplantation of isolated mitochondria to injured heart tissue leads to decreases in cell death, increases in energy production, and improvements in contractile function. We also discovered that exogenously-derived mitochondria injected or perfused into ischemic hearts were readily internalized by cardiac cells through actin-dependent endocytosis. Here, we describe the use of three-dimensional super-resolution microscopy and transmission electron microscopy to determine the intracellular fate of exogenous mitochondria in non-dividing human iPS-derived cardiomyocytes and dividing primary human cardiac fibroblasts. We show isolated mitochondria are internalised in human cardiac cells within minutes and then transported to endosomes and lysosomes. The majority of exogenous mitochondria escape from these compartments and fuse with the endogenous mitochondrial network, while some organelles are degraded through hydrolysis. Understanding this process may guide the development of treatments directed at replacing or augmenting impaired mitochondria in ischemic tissues and provide new options to rejuvenate dysfunctional mitochondria in a wide range of human diseases and disorders.

cell biology↗