Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease

© 2019 Lack of growth potential of available grafts represents a bottleneck in the correction of congenital heart defects. Here we used a swine small intestinal submucosa (SIS) graft functionalized with mesenchymal stem cell (MSC)-derived vascular smooth muscle cells (VSMCs), for replacement of the pulmonary artery in piglets. MSCs were expanded from human umbilical cord blood or new-born swine peripheral blood, seeded onto decellularized SIS grafts and conditioned in a bioreactor to differentiate into VSMCs. Results indicate the equivalence of generating grafts engineered with human or swine MSC-derived VSMCs. Next, we conducted a randomized, controlled study in piglets (12–15 kg), which had the left pulmonary artery reconstructed with swine VSMC-engineered or acellular conduit grafts. Piglets recovered well from surgery, with no casualty and similar growth rate in either group. After 6 months, grafted arteries had larger circumference in the cellular group (28.3 ± 2.3 vs 18.3 ± 2.1 mm, P < 0.001), but without evidence of aneurism formation. Immunohistochemistry showed engineered grafts were composed of homogeneous endothelium covered by multi-layered muscular media, whereas the acellular grafts exhibited a patchy endothelial cell layer and a thinner muscular layer. Results: show the feasibility and efficacy of pulmonary artery reconstruction using clinically available grafts engineered with allogeneic VSMCs in growing swine

Evaluation et traitement de la douleur chez la vache suite à une intervention chirurgicale

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Early Reactional Hyperplasia and Neuronal Differentiation of the Ciliary Epithelium (CE) in Experimental Retinal Detachment (RD) with Proliferative VitreoRetinopathy (PVR) in the Porcine Eye

Background: Rare quiescent retinal progenitor cells have been isolated in the adult amphibian ciliary marginal zone (Hollyfield, 1968), then in the mammalian (Tropepe et al, 2000) (Ahmad et al, 2000) (Fischer and Rey, 2000) and human CE (Coles et al, 2004) (Ballios et al, 2011). This contingent might be inhibited in the adult eye by the signaling pathway ephrin (Chen, personal communication, ARVO 2012, submitted, Stem Cells). Retinal injury might be a triggering factor to quit the dormant state in the adult mammalian CE (Ooto, 2004) (Nickerson, 2007) (Nishiguchi 2008) (Kiyama et Wang, 2010), as it has been demonstrated also in the human brain (Moe et al, 2005) (Logan et al, 2006) . We have reported a CE proliferation with retinal neuronal and photoreceptor differentiation in three human eyes eviscerated for longstanding RD and PVR (Ducournau et al 2012). The CE strongly expressed EGFR. The concept of niche (Fischer and Rey, 2003) is now well established in stem cells recruitment processes. We have hypothezised that the disease RD and PVR might stimulate a dormant population of Retinal Progenitor Cells (RPCs) in the CE in the human eye in vivo in presence of a niche constituted by EGF. Proliferation in the ciliary body, together with nestin expression in ciliary MCM2+ (macrophage/microglia marker F4/80) cells were found in mice eyes with experimental RD, suggesting that RD might activate putative RPCs (Suburo et al, 2010). The aim of the present work was to study the CE in the porcine eye with experimental DR and PVR

Respiratory oscillations in alveolar oxygen tension measured in arterial blood

Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome

Respiratory oscillations in alveolar oxygen tension measured in arterial blood.

Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome