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PubMed2005

From stem cells to viable autologous semilunar heart valve.

BACKGROUND: An estimated 275,000 patients undergo heart valve replacement each year. However, existing solutions for valve replacement are complicated by the morbidity associated with lifelong anticoagulation of mechanical valves and the limited durability of bioprostheses. Recent advances in tissue engineering and our understanding of stem cell biology may provide a lifelong solution to these problems. METHODS AND RESULTS: Mesenchymal stem cells were isolated from ovine bone marrow and characterized by their morphology and antigen expression through immunocytochemistry, flow cytometry, and capacity to differentiate into multiple cell lineages. A biodegradable scaffold was developed and characterized by its tensile strength and stiffness as a function of time in cell-conditioned medium. Autologous semilunar heart valves were then created in vitro using mesenchymal stem cells and the biodegradable scaffold and were implanted into the pulmonary position of sheep on cardiopulmonary bypass. The valves were evaluated by echocardiography at implantation and after 4 months in vivo. Valves were explanted at 4 and 8 months and examined by histology and immunohistochemistry. Valves displayed a maximum instantaneous gradient of 17.2+/-1.33 mm Hg, a mean gradient of 9.7+/-1.3 mm Hg, an effective orifice area of 1.35+/-0.17 cm2, and trivial or mild regurgitation at implantation. Gradients changed little over 4 months of follow-up. Histology showed disposition of extracellular matrix and distribution of cell phenotypes in the engineered valves reminiscent of that in native pulmonary valves. CONCLUSIONS: Stem-cell tissue-engineered heart valves can be created from mesenchymal stem cells in combination with a biodegradable scaffold and function satisfactorily in vivo for periods of >4 months. Furthermore, such valves undergo extensive remodeling in vivo to resemble native heart valves.

Animals↗
PubMed1989

Perception of mechanical heart valve sounds.

Most currently used mechanical heart valve prostheses generate a distinct sound when they close. This sound is sometimes disturbing to the patient, and may impair quality of life. In a study of 285 patients followed up for a mean of 2.5 years after mechanical heart valve replacement, one-third were sometimes disturbed by sounds emanating from the prosthesis. Older patients were less disturbed than young ones, but whether this could be explained by age-related impairment of hearing ability (presbyacusis) was not possible to determine. Prosthetic size, implantation site, patient's weight, body surface area and type of prosthesis did not statistically differ according to experience of prosthetic sounds. Although few patients were seriously disturbed by these sounds, it is hoped that mechanical heart valves of the future will function more quietly.

Age Factors↗
PubMed1987

Results of a comparative in vitro study of Duromedics and Björk-Shiley monostrut mitral heart valve prostheses.

Two different mechanical heart valves with annulus diameters 21-29 mm, (five Björk-Shiley monostrut tilting disc valves and five Duromedics bileaflet valves) have been tested in pulsatile flow in the mitral position of a mock circulation. Reflux, pressure, and orifice area have been measured while cardiac output was varied between 2 and 6 1 min-1. Insufficiency, mean orifice area, discharge coefficient, and performance and efficiency indices have been calculated. Mean values of insufficiency for the Björk-Shiley monostrut valves varied between 4.8 and 17.2% while the corresponding values for the Duromedics valves were in the range 6.1-17.3%. Mean values for orifice areas of the Björk-Shiley monostrut valves increased with the larger valve sizes from 101.1 to 210.2 mm2; for the Duromedics valves the area range was 134.5-262.9 mm2. Because of the larger orifice areas the values of discharge coefficient and performance index for the Duromedic valves were higher than those for the Björk-Shiley monostrut valves. As the insufficiency of the two mechanical valves was similar, and the orifice area of the bileaflet valves was greater than that of the tilting disc valves, Duromedics valves gave higher valves for the efficiency index, which varied between 0.31 and 0.39; for Björk-Shiley monostrut valves the index varied between 0.24 and 0.28 under the same test conditions. This hydrodynamic in vitro comparison of mechanical heart valves showed that the Duromedics bileaflet valves were superior to the Björk-Shiley tilting disc valves.

Biomedical Engineering↗
PubMed2006

Atomic force microscopy and FT-IR spectroscopy investigations of human heart valves.

Human aortic, mitral, tricuspid and pulmonary heart valves were investigated by the contact mode atomic force microscopy (AFM) in air, and using FT-IR spectroscopy in the frequency range 950-4000 cm(-1). Heart valves were collected post mortem from 65-78 years old patients who died from non-cardiac diseases. All of the examined valves showed considerable heterogeneity in the surface topography of collagen fibrils as well as in their organization on the tissue surface. The AFM images revealed areas with significantly different spatial organization of the collagen fibril bundles. We observed zones with multidirectional, stacked collagen fibrils as well as areas of thin fibrils packed regularly, densely and "in phase". The majority of the collagen fibrils reproduced the typical transverse D-banding pattern, with the band interval varying in rather wide range of 70-90 nm. Using AFM imaging, objects that correspond to some pathological states of heart valves at their early stages, i.e. some forms of mineral deposits, were observed. The FT-IR spectra allowed us to recognize main components, i.e. collagen and elastin, in di.erent layers (ventricularis, fibrosa) of the valve leaflets as well as they gave also support for the presence of mineral deposits on the valve surface. The presented results showed, that the AFM imaging and FT-IR spectroscopy can be applied as a complementary methods for structural characterization of heart valves at the molecular and supramolecular levels.

Aged↗
PubMed1997

Self management of oral anticoagulant therapy after heart valve replacement.

OBJECTIVE: Patients with mechanical heart valves require lifelong oral anticoagulant treatment which entails frequent blood sampling and dosage adjustment. The purpose of this study was to investigate the feasibility of letting heart valve operated patients manage blood specimen analysis and dosage adjustment themselves. METHODS: A total of 21 patients were enrolled in the study and followed for at least 9 months postoperatively. Immediately after the heart valve operation they were trained in operating a CoaguChek international normal ratio (INR) monitor to analyze capillary whole blood samples. Subsequently training in dosage adjustment was accomplished and all patients were considered fully capable of self management after 30 weeks. In the training period, parallel laboratory INR measurements were made at 3-4 week intervals for reference. A control group of 20 patients was matched, respectively, to the study group. The INR target range was 2.0-3.0. RESULTS: Out of the 21 study patients 19 continued self management beyond 9 months. The median INR value obtained with the monitor was within therapeutic target range for all study patients and only 15 out of 20 control patients were within this range. The mean systematic deviation between laboratory and CoaguChek INR was 7.8% but each patient had a constant characteristic deviation from -11 to +21%. The study patients were within therapeutic target range 77% of the time compared with 53% for the control patients. CONCLUSIONS: Self management of oral anticoagulation is feasible for selected patients and constitutes a significant service improvement compared with conventional management. The CoaguChek monitor seems sufficiently accurate and reliable for self testing and the treatment quality is comparable or even better than conventional management. Assessment of the rate of bleeding and thrombo-embolic events shall be settled in studies comprising larger number of patients.

Administration, Oral↗
PubMed2003

A tissue engineered heart valve implanted in a juvenile sheep model.

BACKGROUND: The tissue-engineered (TE) heart valve was developed to improve the durability of tissue heart valves. The aim of this study was to evaluate morphological and histological changes in a TE heart valve consisting of decellularized porcine matrices seeded with viable autologous vascular endothelial cells (AVEC). MATERIAL/METHODS: TE valves were implanted into the right ventricular outflow tract of eight juvenile sheep and explanted after 7 days, 3 and 6 months. The valves were evaluated visually, by invasive pressure measurements, X-ray, light microscopy, scanning, and transmission electron microscopy. The calcium content of the cusps was determined quantitatively by atomic absorption spectrometry. RESULTS: After valve implantation, all animals showed fast recovery with no complications during the observation period. Invasive pressure measurements presented a mean TE valve pressure gradient of 1.5+/-0.5 mm Hg at 3 and the same at 6 months. Light microscopy showed a monolayer of AVEC on all explanted heart valves, confirmed by scanning electron microscopy and immunohistochemical staining. X-ray examination of explanted TE heart valves showed no cusp calcification, confirmed by atomic absorption spectrometry. CONCLUSIONS: All explanted TE heart valves showed AVEC at the inner surface and ingrowth of fibroblast into the decellularized matrix, increasing during the observation period. The calcium contents were very low at explantation in these viable new heart valves.

Animals↗
PubMed1979

Measurement of haemolysis in patients with prosthetic heart valves.

Haemolysis following prosthetic heart valve insertion can be precisely and sensitively measured by means of a 59Fe ferrokinetic technique. Results obtained in a small series of patients with either Starr-Edwards or Brunwald-Cutter valve replacement are presented.

Aortic Valve↗
PubMed1988

Degenerative pathologic findings after long-term implantation of bovine pericardial bioprosthetic heart valves.

Degeneration of bioprosthetic heart valves constitutes the most important limitation to their long-term durability and the factor that avoids a wider clinical use of these devices. We studied 26 degenerated bovine pericardial valves that belong to a series of 55 prostheses explanted for various reasons. Age of the patients at implantation of the valve and other factors predisposing to primary tissue failure did not seem to significantly influence the results obtained. Mean implantation time was longer for aortic than for mitral valves (p less than 0.05). Also, the mode of failure was different for mitral and aortic prostheses. Tearing of one or more leaflets without mineralization was more frequent (p less than 0.0025) among mitral than among aortic specimens. Coverage of the valve cusps by a macroscopically visible host sheath was more extensive on the outflow than on the inflow aspect (p less than 0.0015 aortic valves; p less than 0.015 mitral valves). On radiological examination the majority of valves had diffuse and severe mineralized lesions. Collagen degeneration was the most frequent histologic lesion to be found in both mineralized and calcium-free valves. Calcification was also frequent and appeared as mineral deposits that extended between different collagen planes. Scanning electron microscopy revealed the almost complete lack of "endothelium-like" cover on any of the valves and exposure of the underlying fibrous components of the pericardial tissue in areas subjected to abrasion. Transmission electron microscopy confirmed the collagen degeneration and disclosed electron-dense microparticles (probably mineralized) both in the extracellular space and within degenerated host connective tissue cells.

Adult↗
PubMed1998

Tissue engineering of heart valves--human endothelial cell seeding of detergent acellularized porcine valves.

OBJECTIVE: Tissue engineering of heart valves represents a new experimental concept to improve current modes of therapy in valvular heart disease. Drawbacks of glutaraldehyde fixed tissue valves or mechanical valves include the short durability or the need for life-long anticoagulation, respectively. Both have in common the inability to grow, which makes valvular heart disease especially problematic in children. The aim of this study was to develop a new methodology for a tissue engineered heart valve combining human cells and a xenogenic acellularized matrix. METHODS: Porcine aortic valves were acellularized by deterging cell extraction using Triton without tanning. Endothelial cells were isolated in parallel from human saphenous veins and expanded in vitro. Specimens of the surface of the acellular matrix were seeded with endothelial cells. Analysis of acellularity was performed by light microscopy and scanning electron microscopy. Cell viability following seeding was assayed by fluorescence staining of viable cells. RESULTS: The acellularization procedure resulted in an almost complete removal of the original cells while the 3D matrix was loosened at interfibrillar zones. However the 3D arrangement of the matrix fibers was grossly maintained. The porcine matrix could be seeded with in vitro expanded human endothelial cells and was maintained in culture for up to 3 days to document the formation of confluent cultures. CONCLUSIONS: Porcine aortic valves can be almost completely acellularized by a non-tanning detergent extraction procedure. The xenogenic matrix was reseeded with human endothelial cells. This approach may eventually lead to the engineering of tissue heart valves repopulated with the patients own autologous cells.

Animals↗
PubMed1986

Antithrombotic therapy in patients with valvular heart disease and prosthetic heart valves.

Indications and the type of antithrombotic therapy for the prevention of thromboembolism in patients with valvular heart disease, mechanical prosthetic heart valves and bioprosthetic heart valves are discussed. The evidence for these clinical recommendations is described and graded into five levels. The indications for anticoagulation in patients with valvular heart disease are chronic or paroxysmal atrial fibrillation, sinus rhythm with a very large left atrium, severe left ventricular dysfunction or presence of heart failure or a history of previous thromboembolism. Anticoagulant therapy is administered to prolong the prothrombin time to 1.5 to 2.0 times control, using rabbit brain thromboplastin (standardized international normalized ratio = 3.0 to 4.5). Risk factors for thromboembolism in patients with prosthetic heart valves are discussed. Because intracardiac thrombus formation may start during and continues early after operation, restarting heparin therapy 6 hours after operation and continuing it for the duration of the hospitalization is advised. For mechanical prosthetic heart valves, oral anticoagulation as outlined plus dipyridamole is advised indefinitely. Platelet inhibitor therapy alone is insufficient. For bioprosthetic heart valves, heparin is followed by oral anticoagulation as outlined for 3 months after mitral or aortic valve replacement and indefinitely after mitral valve replacement if there is atrial fibrillation or a very large left atrium; aspirin may be recommended indefinitely after aortic valve replacement. Antithrombotic therapy is also considered for four special situations: noncardiac surgery, prosthetic valve endocarditis, anticoagulation after a thromboembolic event, and antithrombotic therapy during pregnancy.

Anticoagulants↗
PubMed2006

Intraoperative and postoperative evaluation of cavitation in mechanical heart valve patients.

BACKGROUND: Cavitation has been claimed partly responsible for the increased risk of thromboembolic complications, hemolysis, and fatal valve failure seen in mechanical heart valve patients. In vivo studies have investigated cavitation using high-pass filtering of the high-frequency pressure fluctuations with the root mean square values as an assessment of intensities. In vitro studies have shown that this well-known method may not be ideal owing to loss of data as a consequence of filtering, and because it requires a priori knowledge of the valve resonance pattern. Therefore, a new method has been developed, which decomposes the signal into nondeterministic (cavitation) and deterministic (valve resonance) signal components, and hence decreases data loss. This study aimed to evaluate cavitation in patients with mechanical, biological, and native heart valves both intraoperatively and postoperatively using the new method. METHODS: High-frequency pressure fluctuations were measured by a hydrophone intraoperatively and postoperatively in 14 patients with mechanical valves, 10 patients with normal aortic valves, and 5 patients with bioprosthesis. The total signal energy was evaluated as nondeterministic and deterministic energies. RESULTS: Nondeterministic energies were verified both intraoperatively and postoperatively in all patients who had a mechanical valve; this finding confirms the cavitation potential of mechanical valves. None of the data recorded in patients with bioprosthetic or native valves contained nondeterministic energy. CONCLUSIONS: The study confirms the presence of cavitation in mechanical heart valve patients using the nondeterministic energy of high-frequency pressure fluctuations as a quantitative measure of cavitation both intraoperatively and postoperatively.

Acoustics↗
PubMed2003

Dynamic impact stress analysis of a bileaflet mechanical heart valve.

BACKGROUND AND AIMS OF THE STUDY: Mechanical heart valves (MHV) are widely used to replace dysfunctional and failed heart valves. The bileaflet MHV is very popular due to its superior hemodynamics. At present, bileaflet MHVs account for about two-thirds of the prosthetic heart valve market. Since their introduction in 1977, the hemodynamics of bileaflet prostheses has been extensively studied. New technologies used to develop MHV include better design concepts, materials, manufacturing processes, and post-design verification. The study aim was to investigate the dynamic impact stress of a newly designed bileaflet MHV under normal physiological conditions. METHODS: Pro/Engineer was used to generate a 3-D model of the designed valve. ANSYS 5.5 and LS-DYNA were used to calculate stress and deformation of the valve. Due to symmetry, a one-half orifice and one leaflet were modeled using the eight-noded hexahedral elements. When valve leaflets are in the fully closed position, the static contact stress between leaflet and orifice was predicated under typical heart valve closing pressure of 80 mmHg. To study the dynamic effects of the closing valve, LS-DYNA was used to simulate leaflet motion. Typical physiological pressure waveform was employed to initiate this leaflet motion. Two types of valve were investigated: Test valve A (size 19, flat leaflet); and test valve B (size 19, tapered leaflet 1.5 degrees, with the same thickness at pivot as valve A). The non-invasive laser sweeping technique was used to measure leaflet closing velocity in a mock flow test rig. The closing velocity of test valve A was compared by experimental and computed results. The corresponding dynamic contact stress on the leaflet was obtained for different modes of loading, simulated under angular velocity, acceleration, and especially under representative pressure waveform. RESULTS: The experimental closing velocity of test valve A was 1.07 +/- 0.05 m/s; the computed value was 1.130 m/s. During full closure, the leaflets showed a slight rebound, and this was also seen experimentally. For test valve B, the computed closing velocity was 1.039 m/s. In the dynamic impact analysis, the physiological pressure waveform was obtained at a normal heart rate of 70 beats/min from the mock flow test rig. Dynamic stress and displacement of the model valve were calculated as the valve was closing. The time step of calculation was determined by the wave propagation velocity and element size. With an interhinge distance of 4.966 mm based on the geometric design of the valve, maximum dynamic von Mises stress appeared near the hinge of the leaflet (26.92 MPa for valve A; 22.36 MPa for valve B). By varying the position of the hinge/pivoting axis (+/- 10%), an optimized valve geometry could be obtained based on minimal impact stress on the valve leaflet. CONCLUSION: Based on closing velocity comparison of valve A, the calculated model and loading conditions were seen to be reasonable. Computational accuracy was satisfied. The tapering feature of the leaflet is designed especially for minimal impact stress at the leaflet contact areas upon impact with the inner walls of the BMHV. These points provide an optimum structure design for the Nanyang Technological University BMHV.

Finite Element Analysis↗
PubMed1986

[Heart valve surgery only after heart catheter study?].

Recently British authors have postulated that in potential candidates for valvular surgery cardiac catheterization can be reserved for a minority of selected situations: when there is discrepancy between clinical and echocardiographic findings, when there is clinical evidence of a diseased ascending aorta and when there is clinical suspicion of coronary artery disease. In order that this manner of proceeding can be generally accepted two basic requirements must be fulfilled: First, in the majority of valvular patients, clinical examination and non-invasive tests including echocardiography, Doppler and radionuclide investigations should be sufficiently reliable not only to make a correct diagnosis but also to assess correctly the severity of the valvular lesion; second, the presence of significant coronary artery stenoses which would render necessary coronary artery bypass grafting in addition to valvular surgery would have to be excluded unequivocally by non-invasive means. In most instances severe valvular stenoses are correctly assessed by non-invasive means although misinterpretations may occur, such as in elderly patients with depressed cardiac output. In patients with moderately severe stenoses decision making based on non-invasive measurements as to whether valvular surgery should be carried out or not is much more difficult because of the limited accuracy of the non-invasive determination of valvular area (2D-echo) or pressure gradient (Doppler). Isolated massive valvular regurgitations can be quantitated by radionuclide angiography. Less severe regurgitations in combined lesions and regurgitations across both the mitral and the aortic valves however, cannot be quantitated by these techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMedDate not supplied

The closing behavior of mechanical aortic heart valve prostheses.

Mechanical artificial heart valves rely on reverse flow to close their leaflets. This mechanism creates regurgitation and water hammer effects that may form cavitations, damage blood cells, and cause thromboembolism. This study analyzes closing mechanisms of monoleaflet (Medtronic Hall 27), bileaflet (Carbo-Medics 27; St. Jude Medical 27; Duromedics 29), and trileaflet valves in a circulatory mock loop, including an aortic root with three sinuses. Downstream flow field velocity was measured via digital particle image velocimetry (DPIV). A high speed camera (PIVCAM 10-30 CCD video camera) tracked leaflet movement at 1000 frames/s. All valves open in 40-50 msec, but monoleaflet and bileaflet valves close in much less time (< 35 msec) than the trileaflet valve (>75 msec). During acceleration phase of systole, the monoleaflet forms a major and minor flow, the bileaflet has three jet flows, and the trileaflet produces a single central flow like physiologic valves. In deceleration phase, the aortic sinus vortices hinder monoleaflet and bileaflet valve closure until reverse flows and high negative transvalvular pressure push the leaflets rapidly for a hard closure. Conversely, the vortices help close the trileaflet valve more softly, probably causing less damage, lessening back flow, and providing a washing effect that may prevent thrombosis formation.

Acceleration↗
PubMed2002

Evaluation of the marker of hypercoagulability prothrombin fragment F 1+2 in patients with mechanical or biological heart valve prostheses.

OBJECTIVE: To investigate whether patients with heart valve prostheses and similar International Normalized Ratios (INR) have the same level of protection against thromboembolic events, that is, whether the anticoagulation intensity is related to the intensity of hypercoagulability suppression. METHODS: INR and plasma levels of prothrombin fragment 1+2 (F1+2) were assessed in blood samples of 27 patients (7 with mechanical heart valves and 20 with biological heart valves) and 27 blood samples from healthy donors that were not taking any medication. RESULTS: Increased levels of F1+2 were observed in blood samples of 5 patients with heart valve prostheses taking warfarin. These findings reinforce the idea that even though patients may have INRs, within the therapeutic spectrum, they are not free from new thromboembolic events. CONCLUSION: Determination of the hypercoagulability marker F1+2 might result in greater efficacy and safety for the use of oral anticoagulants, resulting in improved quality of life for patients.

Administration, Oral↗
PubMed1995

Processing of prosthetic heart valve sounds for single leg separation classification.

People with serious heart conditions have had their expected life span extended considerably with the development of the prosthetic heart valve especially with the great strides made in valve design. Even though the designs are extremely reliable, the valves are mechanical and operating continuously over a long period; therefore structural failures can occur due to fatigue. In this paper acoustical signal processing techniques developed to process noisy heart valve sounds measured by a sensitive, surface contact microphone are discussed. Measuring heart sounds noninvasively in a noisy environment puts more demands on the signal processing to extract the desired signals from the noise. Heart valve sounds are short-duration (10-20 ms) transients and therefore nonstationary, requiring more sophisticated processing algorithms to achieve the desired signal-to-noise ratios. In this paper the preclassification signal processing is concentrated on exclusively. That is, the signal processing operations performed on the heart valve sounds prior to classification are discussed--a subject that will be developed in a future paper. Efforts are concentrated on the sounds corresponding to the heart valve opening cycle. Valve opening and closing acoustics present additional information about the outlet strut condition--the structural component implicated in valve failure. The importance of the opening sound for single leg separation detection/classification is based on the fact that as the valve opens, the disk passively hits the outlet strut. The opening sounds thus yield direct information about outlet strut condition with minimal amount of disturbance caused by the energy radiated from the disk. Hence the opening sound is a very desirable acoustic signal to extract. Unfortunately, the opening sounds have much lower signal levels relative to the closing sounds and therefore noise plays a more significant role than during the closing event. Because of this it is necessary to screen the sounds for outliers in order to insure a high sensitivity of classification. Because of the sharp resonances appearing in the corresponding spectrum, a parametric processing approach is developed based on an autoregressive model which was selected to characterize the sounds emitted by the Bjork-Shiley convexo-concave (BSCC) valve during opening cycle. First the basic signals and the extraction process used to create an ensemble of heart valve sounds are briefly discussed. Next, a beat monitor capable of rejecting beats that fail to meet an acceptance criteria based on their spectral content is developed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustics↗
PubMed2003

[Pregnancy in patients with prosthetic heart valves].

In women with prosthetic heart valves, pregnancy carry a risk for both mother and fetus, requiring an obstetrical and cardiological management at an optimal level. We performed a systematic review of the literature to estimate the maternal and fetal complications and in order to offer pregnant women carrying a prosthetic heart valve the most practical approach enabling reduction of these risks. As there are no available controlled clinical trials, larger prospective studies are needed to provide guidelines for effective antithrombotic therapy.

Anticoagulants↗
PubMed2006

BMP and FGF regulatory pathways control cell lineage diversification of heart valve precursor cells.

The atrioventricular heart valve leaflets and chordae tendineae are composed of diverse cell lineages and highly organized extracellular matrices that share characteristics with cartilage and tendon cell types in the limb buds and somites. During embryonic chicken valvulogenesis, aggrecan and sox9, characteristic of cartilage cells, are observed in the AV valve leaflets, in contrast to tendon-associated genes scleraxis and tenascin, present in the chordae tendineae. In the limb buds and somites, cartilage cell lineage differentiation is regulated by BMP2, while FGF4 controls tendon cell fate. The ability of BMP2 and FGF4 to induce similar patterns of gene expression in heart valve precursor cells was examined. In multiple assays of cells from prefused endocardial cushions, BMP2 is sufficient to activate Smad1/5/8 phosphorylation and induce sox9 and aggrecan expression, while FGF4 treatment increases phosphorylated MAPK (dpERK) signaling and promotes expression of scleraxis and tenascin. However, these treatments do not alter differentiated lineage gene expression in valve progenitors from fused cushions of older embryos. Together, these studies define regulatory pathways of AV valve progenitor cell diversification into leaflets and chordae tendineae that share inductive interactions and differentiation phenotypes with cartilage and tendon cell lineages.

Animals↗