Search

Background: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats., Methods: rat BMSCs were harvested and cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization., Results: Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility., Conclusion: Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting angiogenesis., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Postinfarction ventricular septal defect (PIVSD) is a devastating mechanical complication following acute myocardial infarction. The management of this pathology is quite challenging, especially in case of complicated cardiogenic shock. The difficulties lie in the timing and type of intervention. Debates exist with regard to immediate versus deferring repair, as well as open repair versus percutaneous closure. The anatomic characteristics and hemodynamic consequence of PIVSD are important elements determining which strategy to adopt, since large septal defect (>15 mm) cannot be appropriately treated by percutaneous occluder devices limiting by their available size, while compromised hemodynamics usually require emergent repair or mechanical support "bridging to surgery". Herein, we report our experience of successful management of a case of cardiogenic shock complicating large PIVSD (38 mm) by delayed surgical repair bridged with Extracorporeal Membrane Oxygenation (ECMO) during 7 days. We emphasize the importance of 3-dimensional transesophageal echocardiography as a decision-making tool.

This study aimed at comparing long-term variations in the perfusion of chronic myocardial infarction (MI) areas after local injections of autologous bone marrow stem cells (BMSCs). 14 coronary ligated rats with transmural chronic MI (4 months) were used: a control group (n = 7) versus a treated group (n = 7) in which (111)In labeled-BMSCs were directly engrafted on MI areas. By using (111)In/(99m)Tc SPECT and Sestamibi gated-SPECT,. left ventricle perfusion and function were monitored in all animals by serial (99m)Tc-Sestamibi pinhole gated-SPECT over a period of 6 months. Post-therapeutic myocardial perfusion improved as early as 48 h following injection in the 2 groups. This benefice was sustained during the 6-month follow-up in the non-engrafted MI-areas from treated rats (at 6-months: +10 ± 5 %), whereas the engrafted ones, as well as the MI areas from control rats, exhibited progressive deterioration over time (at 6-months: -9 ± 10 % and -5 ± 3 %, respectively). Perfusion enhancement of the chronic MI areas treated by BMSCs transplantation is: (1) marked in the following days, presumably because of an unspecific inflammatory reaction, and (2) sustained over the long term but only outside the sites of cell engraftment, suggesting a distant paracrine effect of transplanted cells.

Background: Tissue engineering scaffold constitutes a new strategy of myocardial repair. Here, we studied the contribution of a patch using autologous mesenchymal stem cells (MSCs) seeded on collagen-1 scaffold on the cardiac reconstruction in rat model of chronic myocardial infarction (MI)., Methods: Patches were cultured with controlled MSCs (growth, phenotype and potentiality). Twenty coronary ligated rats with tomoscingraphy (SPECT)-authenticated transmural chronic MI were referred into a control group (n = 10) and a treated group (n = 10) which beneficiated an epicardial MSC-patch engraftment. Contribution of MSC-patch was tested 1-mo after using non-invasive SPECT cardiac imaging, invasive hemodynamic assessment and immunohistochemistry., Results: 3D-collagen environment affected the cell growth but not the cell phenotype and potentiality. MSC-patch integrates well the epicardial side of chronic MI scar. In treated rats, one-month SPECT data have documented an improvement of perfusion in MI segments compared to control (64 ± 4% vs 49 ± 3% p = 0.02) and a reduced infarction. Contractile parameter dp/dtmax and dp/dtmin were improved (p & 0.01). Histology showed an increase of ventricular wall thickness (1.75 ± 0.24 vs 1.35 ± 0.32 mm, p &0.05) and immunochemistry of the repaired tissue displayed enhanced angiogenesis and myofibroblast-like tissue., Conclusion: 3D-MSC-collagen epicardial patch engraftment contributes to reverse remodeling of chronic MI.

Purpose: Up to now, there has been limited investigation into cell therapy in the chronic phase of severe myocardial infarction (MI), and many questions remain concerning the contribution of the engrafted cells and especially their impact on the reperfusion of MI areas, when assessed by objective quantitative imaging techniques. This randomized pilot SPECT, PET, and MRI study was aimed at assessing the effects of bone marrow mononuclear cells (BMNCs) when implanted in areas of severe and chronic MI., Materials and Methods: Fourteen patients, who were referred for coronary artery bypass grafting (CABG) and in whom a screening MIBI-SPECT revealed severely damaged myocardium (<50% uptake under nitrate), were randomized between a cell therapy group (n = 7; CABG and injection of BMNCs within MI areas) and a control group (n = 7; CABG alone)., Results: The MI areas exhibited a posttherapeutic enhancement in the rest-uptake of MIBI in the cell therapy group [difference between 6-month control and baseline: +6.8% (5.4%), P = 0.03] but not in the control group [+1.0% (4.3%)]. However, in a per-patient analysis, this improvement was significant (> +9%) in only 3 cell therapy patients, whose MI areas before therapy had a higher FDG uptake [59% (9%) vs 38% (8%), P = 0.03] and a lower transmural extent at MRI [40% (6%) vs 73% (18%), P = 0.03] when compared with the other cell therapy patients., Conclusions: Perfusion enhancement, obtained with BMNCs in areas of chronic MI, might require an intermediate level of viability documented with FDG-PET and MRI and that totally necrotic MI seems refractory to this cell therapy technique.

Unlabelled: Cell therapy-induced changes in the perfusion of areas of myocardial infarction (MI) remain unclear. This study investigated whether an original pinhole SPECT technique could be applied to a rat MI model to analyze local improvement in myocardial perfusion relating to engraftment sites of bone marrow-derived stem cells (BMSCs)., Methods: Four-month-old MI rats were either untreated (n = 8) or treated (n = 10) by intramyocardial injection of (111)In-labeled BMSCs. Early distribution of (111)In-BMSCs within the MI target was evidenced by dual (111)In/(99m)Tc pinhole SPECT 48 h later. Myocardial perfusion was serially monitored by (99m)Tc-sestamibi pinhole gated SPECT up to 3 mo after transplantation., Results: Forty-eight hours after transplantation, (111)In-BMSCs were observed in all treated rats and in 18 of their 32 underperfused MI segments (<70% sestamibi uptake before transplantation). During the subsequent 3-mo follow-up, the perfusion of MI segments worsened in untreated rats (absolute change in sestamibi uptake, -3% +/- 3%; P < 0.05) but improved in treated rats (+4% +/- 7%; P < 0.05). This perfusion improvement was unrelated to the initial detection of (111)In-BMSCs (+2% +/- 6% in segments with (111)In-BMSCs vs. +5% +/- 7% in those without; not statistically significant) but was strongly associated with less severe perfusion defects before transplantation (+6% +/- 6% in segments with 60%-70% sestamibi uptake [n = 19] vs. -1% +/- 6% in those with <60% uptake [n = 13]; P = 0.003)., Conclusion: When BMSCs are injected within chronic MI, perfusion enhancement predominates in the MI areas showing a high enough residual perfusion before treatment but not in those of the initial cell engraftment, giving evidence of dependency on the perfusion and metabolic environment at implantation sites.

Contexte: Le potentiel angiogénique des cellules souches médullaires n’a pas encore été évalué dans le traitement de l’infarctus du myocarde de type chronique (IDMc), en particulier au niveau des segments nécrotiques réfractaires aux techniques de revascularisation conventionnelle. Objectif: Cet essai clinique prospectif preuve de concept (phase II/III) avait comme objectifs principaux (i) de tester l’innocuité de l’implantation intramyocardique des cellules mononucléées (CMNs) autologues et (ii) d’évaluer l’impact précoce de cette réhabilitation cellulaire sur la reperfusion des segments IDMc. Méthodes: 14 patients, présentant un IDMc > 2mois avec une taille d’IDM > 10 % du VG et une FEVG > 30 et < 50 % sur des critères tomoscintigraphiques (SPECT), ont été répartis de façon aléatoire vers une revascularisation coronarienne optimale seule (Groupe Témoin, n=7) ou associée à une implantation de CMNs (20 à 40 injections, 25×107 à 100×107 cellules) (Groupe Cellule, n=7). Résultats: A un mois post-thérapeutique, une reperfusion significative a été observée à l’examen SPECT (Groupe Cellule=+12±16 % vs Groupe Témoin=-3±8 %, p<0,05). La FEVG a été majorée dans les deux groupes (Groupe Cellule=+4±6 % vs Groupe Témoin=+3±5 %, p=NS) avec une meilleure réduction des volumes systoliques (VTS) et diastoliques (VTD) chez le groupe Cellule comparé aux Témoins : VTS=65±24ml vs 90±17ml, p=0,048; VTD=118±43ml vs 148±21ml, p=0,0503). Le recul d’un an n’a montré aucune différence significative en ce qui concerne le critère d’évaluation primaire rassemblant la morbidité post-opératoire (hémorragie, troubles du rythme), tous les événements cardio-vasculaires majeurs et l’amélioration du statut NYHA. Conclusions: La réhabilitation cellulaire des segments myocardiques sous-perfusés réfractaires aux techniques conventionnelles (i) est faisable sans manifestations indésirables majeures et (2) permet d’accroître la reperfusion tissulaire locorégionale. Le bénéfice thérapeutique à long terme reste à déterminer. [Copyright &y& Elsevier]

Introduction: L’implantation intramyocardique des cellules souches mésenchymateuses (CSMs) améliore la reperfusion de l’infarctus myocardique chronique (IMc). Cependant, l’effet thérapeutique à long terme, après des phénomènes inflammatoires consécutifs aux injections cellulaires, n’est pas élucidé. Cette étude préclinique randomisée avait pour but d’évaluer les variations temporelles des segments IMc traités avec des CSMs. Méthodes: 14 rats (IDMc>4 mois) étaient répartis entre le groupe contrôle (injection de liquide physiologique, n=7) ou le groupe traité recevant une injection de 2x106 CSM préalablement marquées à 111In-oxine (n=7). L’évaluation de la distribution des greffons CSMs se faisait grâce aux examens SPECT 111In/99mTc à 48 Heures et la perfusion par un monitorage séquentiel au Sestamibi pinhole gated-SPECT (avant et pendant 6 mois après traitement). Résultats: L’examen post-thérapeutique à 48 H a montré une majoration significative de la reperfusion myocardique du groupe contrôle (+ 8 ±5 % en terme de % d’augmentation de la captation de Sestamibi) et du groupe thérapie (zone traitée=+13±15 % et zones avoisinantes +7±7 %). Cette augmentation était persistante durant les 6 mois de suivi dans les segments avoisinants de greffe cellulaire (+10±5 %) alors qu’elle déclinait progressivement aussi bien dans les zones traitées (groupe thérapie=-9±10 %) que dans celles recevant le liquide physiologique (groupe contrôle=-5±3 %). Conclusions: L’augmentation de la perfusion myocardique de zones IMc suite à l’implantation de CSMs est (i) précoce et probablement associée à de réactions inflammatoires non-spécifiques et (ii) soutenue à long terme surtout dans les zones éloignées des sites d’implantations suggérant un effet paracrine des CSMs. [Copyright &y& Elsevier]