Prolonged Cardiopulmonary Bypass Time-Induced Endothelial Dysfunction via Glypican-1 Shedding, Inflammation, and Matrix Metalloproteinase 9 in Patients Undergoing Cardiac Surgery.

Objectives: A prolonged cardiopulmonary bypass (CPB) time of over 180 min is linked to poorer outcomes and higher mortality in cardiac surgery. This study examines how glypican-1 shedding, matrix metallopeptidase 9 (MMP9), and the pro-inflammatory cytokine IL-1β may contribute to endothelial dysfunction in patients undergoing on-pump surgery with an extended CPB.

Methods: Fifty-one patients undergoing cardiac surgical procedures were divided into two groups based on the intraoperative CPB duration: (i) normal CPB (<180 min, = 23) and (ii) prolonged CPB (>180 min, = 28).

Bioprinted optoelectronically active cardiac tissues.

Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation-induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light.

Ultrathin rubbery bio-optoelectronic stimulators for untethered cardiac stimulation.

Untethered electrical stimulation or pacing of the heart is of critical importance in addressing the pressing needs of cardiovascular diseases in both clinical therapies and fundamental studies. Among various stimulation methods, light illumination-induced electrical stimulation via photoelectric effect without any genetic modifications to beating cells/tissues or whole heart has profound benefits. However, a critical bottleneck lies in the lack of a suitable material with tissue-like mechanical softness and deformability and sufficient optoelectronic performances toward effective stimulation.

Machine Learning Assisted Stroke Prediction in Mechanical Circulatory Support: Predictive Role of Systemic Mitochondrial Dysfunction.

Stroke continues to be a major adverse event in advanced congestive heart failure (CHF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. Abnormalities in mitochondrial oxidative phosphorylation (OxPhos) have been critically implicated in the pathogenesis of neurodegenerative diseases and cerebral ischemia. We hypothesize that prior stroke may be associated with systemic mitochondrial OxPhos abnormalities, and impaired more in post-CF-LVAD patients with risk of developing new stroke.

Quality Assessment of Long-Term Cryopreserved Human Bone-Derived Marrow Mesenchymal Stromal Cell Samples: Experience from the Texas Heart Institute Biorepository and Biospecimen Profiling Core.

In biomedical research, biorepositories are pivotal resources that safeguard and supply clinical samples for scientific investigators. Proper long-term cryopreservation conditions are essential to maintain biospecimen quality. In this study, we analyzed the efficacy of sample cryopreservation at the Texas Heart Institute Biorepository and Biospecimen Profiling Core (THI-BRC).

Long-Term, Sex-Specific Effects of GCRsim and Gamma Irradiation on the Brains, Hearts, and Kidneys of Mice with Alzheimer's Disease Mutations.

Understanding the hazards of space radiation is imperative as astronauts begin voyaging on missions with increasing distances from Earth's protective shield. Previous studies investigating the acute or long-term effects of specific ions comprising space radiation have revealed threats to organs generally considered radioresistant, like the brain, and have shown males to be more vulnerable than their female counterparts. However, astronauts will be exposed to a combination of ions that may result in additive effects differing from those of any one particle species.

Laminin Alpha 2 Enhances the Protective Effect of Exosomes on Human iPSC-Derived Cardiomyocytes in an In Vitro Ischemia-Reoxygenation Model.

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart.

NADPH oxidase overexpression and mitochondrial OxPhos impairment are more profound in human hearts donated after circulatory death than brain death.

This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups ( = 6) based on different WITs (20, 40, and 60 min).

New Biomarkers for Cardiovascular Disease.

Cardiovascular disease is the leading cause of death and disability worldwide. Early detection and treatment of cardiovascular disease are crucial for patient survival and long-term health. Despite advances in cardiovascular disease biomarkers, the prevalence of cardiovascular disease continues to increase worldwide as the global population ages.

Myocardial edema, inflammation, and injury in human heart donated after circulatory death are sensitive to warm ischemia and subsequent cold storage.

Background: Single-dose del Nido solution was recently used in human donation after circulatory death (DCD) heart procurement. We compared the effect of del Nido cardioplegia on myocardial edema, inflammatory response, and injury in human DCD hearts and human donation after brain death (DBD) hearts with different warm ischemic times (WIT) and subsequent cold saline storage times (CST).

Methods: A total of 24 human hearts, including 6 in the DBD group and 18 in the DCD group-were procured for the research study.

Primary Graft Dysfunction in Lung Transplantation: A Review of Mechanisms and Future Applications.

Lung allograft recipients have worse survival than all other solid organ transplant recipients, largely because of primary graft dysfunction (PGD), a major form of acute lung injury affecting a third of lung recipients within the first 72 h after transplant. PGD is the clinical manifestation of ischemia-reperfusion injury and represents the predominate cause of early morbidity and mortality. Despite PGD's impact on lung transplant outcomes, no targeted therapies are currently available; hence, care remains supportive and largely ineffective.

Polymerized Laminin-521: A Feasible Substrate for Expanding Induced Pluripotent Stem Cells at a Low Protein Concentration.

Laminins (LNs) play a central role in the self-assembly and maintenance of basement membranes and are involved in critical interactions between cells and other extracellular matrix (ECM) proteins. Among the defined, xeno-free ECM culture matrices, LNs-namely LN521-have emerged as promising coating systems for the large-scale expansion of induced pluripotent stem cells (iPSCs). The biologic activity of LNs is enhanced by their acidification-induced self-polymerization into a cell-associated network called polylaminin (polyLN), which can recapitulate the native-like polymeric array in a cell-free system.

Effect of intraoperative support mode on circulating inflammatory biomarkers after lung transplantation surgery.

Background: Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection.

Methods: We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off-pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion.

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis.

The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant.

Mining the Mesenchymal Stromal Cell Secretome in Patients with Chronic Left Ventricular Dysfunction.

Close examination of the initial results of cardiovascular cell therapy clinical trials indicates the importance of patient-specific differences on outcomes and the need to optimize or customize cell therapies. The fields of regenerative medicine and cell therapy have transitioned from using heterogeneous bone marrow mononuclear cells (BMMNCs) to mesenchymal stromal cells (MSCs), which are believed to elicit benefits through paracrine activity. Here, we examined MSCs from the BMMNCs of heart failure patients enrolled in the FOCUS-CCTRN trial.

Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation.

Background: Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men's and women's clinical and molecular responses to post-LTx IR.

Methods: In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD).

Restoring anatomical complexity of a left ventricle wall as a step toward bioengineering a human heart with human induced pluripotent stem cell-derived cardiac cells.

The heart is a highly complex, multicellular solid organ with energy-demanding processes that require a dense vascular network, extensive cell-cell interactions, and extracellular matrix (ECM)-mediated crosstalk among heterogeneous cell populations. Here, we describe the regeneration of left ventricular (LV) wall using decellularized whole rabbit heart scaffolds recellularized exclusively with human induced pluripotent stem cell-derived endothelial cells, cardiomyocytes, and other cardiac cell types. Cells were sequentially delivered to the scaffold using an optimized endothelial cell:cardiomyocyte media.

Decellularized Extracellular Matrix Powder Accelerates Metabolic Maturation at Early Stages of Cardiac Differentiation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

During fetal development, cardiomyocytes switch from glycolysis to oxidative metabolism to sustain the energy requirements of functional cells. State-of-the-art cardiac differentiation protocols yield phenotypically immature cardiomyocytes, and common methods to improve metabolic maturation require multistep protocols to induce maturation only after cardiac specification is completed. Here, we describe a maturation method using ventricle-derived decellularized extracellular matrix (dECM) that promoted early-stage metabolic maturation of cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs).

Incidence of primary graft dysfunction is higher according to the new ISHLT 2016 guidelines and correlates with clinical and molecular risk factors.

Background: Primary graft dysfunction (PGD) is the most important determinant of morbidity and mortality after lung transplantation, but its definition has evolved over the past decade. The implications of this refinement in clinical definition have not been evaluated. In this single-center study, we compared PGD incidence, risk factors, and outcomes using the 2005 and the updated-2016 International Society of Heart and Lung Transplantation guidelines for PGD grading in lung transplant patients.

Characterization of perfusion decellularized whole animal body, isolated organs, and multi-organ systems for tissue engineering applications.

To expand the application of perfusion decellularization beyond isolated single organs, we used the native vasculature of adult and neonatal rats to systemically decellularize the organs of a whole animal in situ. Acellular scaffolds were generated from kidney, liver, lower limb, heart-lung system, and a whole animal body, demonstrating that perfusion decellularization technology is applicable to any perfusable tissue, independent of age. Biochemical and histological analyses demonstrated that organs and organ systems (heart-lung pair and lower limb) were successfully decellularized, retaining their extracellular matrix (ECM) structure and organ-specific composition, as evidenced by differences in organ-specific scaffold stiffness.

Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database.

Sex-based differences are under-studied in cardiovascular trials as women are commonly underrepresented in dual sex studies, even though major sex-based differences in epidemiology, pathophysiology, and outcomes of cardiovascular disease have been reported. We examined sex-based differences in patient characteristics, outcome, and BM-CD34+ frequency of the ACCRUE (Meta-Analysis of Cell-based CaRdiac studies) database involving patients with acute myocardial infarction (AMI) randomized to autologous cell-based or control treatment. We compared baseline characteristics and 1-year follow-up clinical data: composite major adverse cardiac and cerebrovascular events (primary endpoint), and changes in left ventricular ejection fraction (LVEF), end-diastolic (EDV), and end-systolic volumes (ESV) (secondary efficacy endpoint) in women and men ( = 1,252; 81.

Cues from human atrial extracellular matrix enrich the atrial differentiation of human induced pluripotent stem cell-derived cardiomyocytes.

New robust and reproducible differentiation approaches are needed to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes of specific subtypes in predictable quantities for tissue-specific disease modeling, tissue engineering, and eventual clinical translation. Here, we assessed whether powdered decellularized extracellular matrix (dECM) particles contained chamber-specific cues that could direct the cardiac differentiation of human iPSCs toward an atrial phenotype. Human hearts were dissected and the left ventricle (LV) and left atria (LA) were isolated, minced, and decellularized using an adapted submersion decellularization technique to generate chamber-specific powdered dECM.

Whole Heart Engineering: Advances and Challenges.

Bioengineering a solid organ for organ replacement is a growing endeavor in regenerative medicine. Our approach - recellularization of a decellularized cadaveric organ scaffold with human cells - is currently the most promising approach to building a complex solid vascularized organ to be utilized in vivo, which remains the major unmet need and a key challenge. The 2008 publication of perfusion-based decellularization and partial recellularization of a rat heart revolutionized the tissue engineering field by showing that it was feasible to rebuild an organ using a decellularized extracellular matrix scaffold.