Structural assessments in decellularized extracellular matrix of porcine semilunar heart valves: Evaluation of cell niches.

Tissue-engineered heart valves aim to reproduce the biological properties of natural valves with anatomically correct structure and physiological performance. The closest alternative to creating an ideal heart valve substitute is to use decellularized porcine heart valves, due to their anatomy and availability. However, the immunological barrier and the structural maintenance limit the long-term physiological performance of decellularized porcine heart valves. This study investigated the extracellular matrix (ECM) structure of aortic and pulmonary porcine valves decellularized by a low concentration sodium dodecyl sulfate (SDS)-based method in order to determine the ECM scaffold (ECMS) conditions related to remodeling potential. To assess the structures of the leaflets and conduits of the heart valves, ECM components and their organization were evaluated by histology, biochemical analysis (BC), scanning electron microscopy, multiphoton microscopy, tensile test, immunofluorescence labeling (IF), and Raman microspectroscopy used to draw a profile of the cell niches. Histology and multiphoton imaging of decellularized aortic and pulmonary leaflets and conduits revealed a collagen and elastin histoarchitecture with rearrangement, loosening fibers, and glycosaminoglycan depletion confirmed by biochemistry quantification. The potential cytotoxicity of SDS residues was eliminated after 10 wash cycles. The mechanical properties of the structure of the valve indicated a functional resistance of decellularized ECM. The IF demonstrated the presence of basement membrane, suggesting a potential structure for host cell attachment. The RM analysis showed evidence of molecular interactions, suggesting conservation of the chemical composition, particularly among the protein molecular structures. The structural analyses performed in the semilunar porcine heart valves demonstrate that decellularized ECMS has structural properties that support physiological performance and potential host tissue integration. In fact, decellularized leaflet scaffolds were prone to cell interaction after human adipose-derived stromal cell seeding and culturing. Further analysis of biocompatibility, particularly the ECM-cell interaction, can elucidate the remodeling process, in preserved decellularized heart valve scaffold.

Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy / Transplante Autólogo de Células-Tronco Adultas para Tratamento da Cardiomiopatia Dilatada Idiopática

Background: Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective: Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods: We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results: During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion: Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. .

Fundamento: Pacientes portadores de cardiomiopatia dilatada idiopática apresentam alta morbimortalidade, mesmo em tratamento clínico otimizado. A infusão autóloga de células-tronco adultas da medula óssea mostrou resultados clínicos preliminares promissores nesses pacientes. Objetivo: Determinar a eficácia do transplante autólogo de células-tronco adultas da medula óssea sobre as funções sistólica e diastólica, e o grau de insuficiência mitral em pacientes portadores de cardiomiopatia dilatada idiopática em classes funcionais NYHA II e III. Métodos: Infundiram-se 4,54 x 108 ± 0,89 x 108 células-tronco adultas da medula óssea nas artérias coronárias de 24 pacientes com cardiomiopatia dilatada idiopática em classes funcionais NYHA II e III. Após 3 meses, 6 meses e 1 ano, avaliaram-se as mudanças de classe funcional, das funções ventricular esquerda sistólica e diastólica, e do grau da insuficiência mitral. Resultados: No seguimento, seis (25%) pacientes melhoraram sua classe funcional e oito (33,3%) mantiveram sua classe funcional inicial. A fração de ejeção ventricular esquerda aumentou 8,9%, 9,7% e 13,6%, após 3 e 6 meses e 1 ano (p = 0,024; p = 0,017 e p = 0,018), respectivamente. A função diastólica ventricular esquerda e o grau de insuficiência mitral não demonstraram mudanças significativas. Dois pacientes (8,3%) receberam cardioversor e ressincronizador implantável. Ocorreram quatro (16,6%) mortes súbitas e quatro (16,6%) mortes por insuficiência cardíaca terminal. A sobrevida média desses oitos pacientes foi de 2,6 anos. Conclusão: A infusão intracoronariana de células-tronco adultas da medula óssea em pacientes com cardiomiopatia dilatada idiopática promoveu melhora ...

Autologous transplantation of bone marrow adult stem cells for the treatment of idiopathic dilated cardiomyopathy.

BACKGROUND: Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. OBJECTIVE: Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. METHODS: We administered 4,54 x 10(8) ± 0,89 x 10(8) bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. RESULTS: During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. CONCLUSION: Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation.