Intramyocardial transplantation of autologous bone marrow mononuclear cells (BMMC) is believed to be a promising method for the treatment of patients with chronic ischemic heart disease. The aim of this study was to evaluate long-term results of intramyocardial bone marrow cell transplantation in patients with severe ischemic heart failure. One hundred nine patients with chronic myocardial infarction and end-stage chronic heart failure were randomized into two groups: 55 patients received intramyocardial BMMC injection and 54 received optimal medical therapy. The NOGA system (Biosense-Webster) was used to administer 41 +/- 16 x 106 BMMC into the border zone of myocardial infarction. None of the patients developed periprocedural complications following BMMC injections. The injections led to improvement of CCS class (3.1 +/- 0.4 to 1.6 +/- 0.6 after 6 months and 1.6 +/- 0.4 after 12 months; p = 0.001) and NYHA functional class (3.3 +/- 0.2 to 2.3 +/- 0.2 after 6 months and 2.5 +/- 0.1 after 12 months; p = 0.006). Left ventricular ejection fraction increased significantly in the BMMC group (27.8 +/- 3.4% vs 32.3 +/- 4.1%; p = 0.04) while it tended to decrease in the control group (26.8 +/- 3.8% to 25.2 +/- 4.1%; p = 0.61). Summed rest score improved in the BMMC group after 12 months (30.2 +/- 5.6 to 27.8 +/- 5.1; p = 0.032). The improvement of stress score was more noticeable (34.5 +/- 5.4 to 28.1 +/- 5.2; p = 0.016). Neither stress nor rest score changed in patients numbers on medical therapy. In BMMC group 6 (10.9%) patients died at 12-month follow-up compared with 21 (38.9%) in control group (log-rank test, p = 0.0007). Intramyocardial bone marrow cell transplantation to patients with ischemic heart failure is safe and improved survival, clinical symptoms, and has beneficial effect on LV function.

Disseminated ossification of the myocardium and severe angiomatosis were detected in sites of implantation of unseparated bone marrow mononuclear fraction cells in dogs with experimental chronic coronary disease. Minor immunocytochemical differences in cells of the mononuclear fraction adhering and not adhering to plastic were found. Significant differences in the expression of mRNA of chondro-osteogenesis genes (aggrecan, lumican, and osteopontin) in adherent and nonadherent cells were detected. The expression of aggrecan gene mRNA was 3-fold lower, of lumican gene 6-fold, and of osteopontin gene 11-fold lower in nonadherent cells compared to adherent fraction.

Laser-induced fluorescence (LIF) spectra of calcified human heart-valve tissue and LIF spectra of macroscopic calcinosis fragments dissected from human heart valves were compared with LIF spectra of pig myocardium tissues. Excitation was provided by an excimer laser with wavelength lambda = 248 nm. Fluorescence bands that were due to mineral and organic tissue components were identified by measurement of LIF spectra of macroscopic fragments of calcified tissues that had been heat treated at 700 degrees C. The studies showed that LIF spectra of calcified tissues include fluorescence emission from tryptophan, collagen, elastin, and a mineral component of tissue, hydroxylapatite. The observed differences in LIF spectra of normal and calcified tissues with different pathologies may result not only from calcification-induced changes in relative collagen and elastin concentrations but also from additional (absent in normal heart tissue) fluorescence of hydroxylapatite. The calcification-induced changes in the LIF spectra of human heart-valve tissues, characterized by a 330/450 nm ratio, were found to be quite appreciable, which suggests that this ratio can be used with LIF measurements to evaluate the degree of heart-tissue calcification.

The review considers the properties of tissue engineered scaffolds required for osteogenic differentiation, cell-cell signaling interactions, and scaffold vascularization, which are largely provided by the scaffold architecture: its porosity and pore sizes, the presence of pore-channel interconnectivity inside the scaffold and its influence on cell-cell interactions. The review shows, based on the literature data, that the geometry of surface, and sizes of pores and canaliculi providing internal communication between the pores in the matrix, and the matrix microarchitecture itself considered even without the influence of growth factors and materials of which the matrices are made can affect the cell proliferation, osteogenic induction, and osteoconductive abilities, which are realized via intercellular communications.

Most studies have confirmed the beneficial effects of autologous bone marrow mononuclear cell (BMMC) transplantation on angina, myocardial perfusion, regional wall motion, and LV ejection fraction (LVEF). Cardiac resynchronization therapy (CRT) has also shown a beneficial effect in patients with heart failure (HF) and electrical/mechanical dyssynchrony. However, the relative contribution of BMMC and CRT in patients with ischemic HF and electromechanical dyssynchrony has never been investigated. The aim of this study was to evaluate the benefit of combining BMMC transplantation with CRT in patients with severe ischemic HF, left bundle branch block (LBBB), and mechanical dyssynchrony. Patients with ischemic HF, LVEF < 35%, LBBB, and mechanical dyssynchrony underwent intramyocardial transplantation of BMMC and CRTD system implantation. This randomized, single-blind, crossover study compared clinical and echocardiographic parameters during two follow-up periods: 6 months of active CRT (BMMC + CRTact) and 6 months of inactive CRT (BMMC + CRTinact). Physical performance was assessed by means of a 6-min walking test. Myocardial perfusion was evaluated by SPECT. Quality of Life (QoL) was assessed through the Minnesota Living with HF Questionnaire (MLwHFQ). Twenty-six patients (64 ± 7 years) were enrolled in the study. The distance covered by the patients during the 6-min walking test significantly increased in the BMMC + CRTinact phase (BMMC therapy only) in comparison with the baseline (269 ± 68 vs 206 ± 51; p = 0.007) and in the BMMC + CRTact phase (BMMC therapy + CRT) in comparison with the BMMC + CRTinact (378 ± 59 vs 269 ± 68; p < 0.001). The summed rest and stress score (SPECT) decreased significantly in the BMMC + CRTact and BMMC + CRTinact phases in comparison with the baseline (p ≤ 0.03). Both phases showed equivalent myocardial perfusion in the segments into which BMMC had been injected. QoL score was significantly lower in the BMMC + CRTinact phase than at the baseline (44.1 ± 14 vs 64.8 ± 19; p < 0.001), and in the BMMC + CRTact phase than in the BMMC + CRTinact phase (26.4 ± 12 vs 44.1 ± 14; p = 0.004). BMMC and CRT seem to act independently on myocardial perfusion and electromechanical dyssynchrony, respectively. Combining these two complementary therapies can significantly improve LV performance in patients with severe HF and electromechanical dyssynchrony.

We performed a fluorescent microscopic examination of human and animal aortic grafts at different stages of decellularization. Treatment of aortic grafts with trypsin/EDTA solution for 48 h leads to their complete decellularization and preserved the connective tissue fiber backbone, which gains a netlike structure. The use of this protocol of decellularization leads to disappearance of subintimal calcium deposits in human aortic grafts. Differences in laser-induced fluorescence spectra of aortas before decellularization and at different stages of this process were revealed. Our findings suggest that the use of fluorescence induced by excimer lasers is promising for identification of the composition of biological tissues, analysis of their state, and the presence of changes.

Morphological and spectral X-ray analysis of carious and noncarious extracted teeth showed the patterns of dentin ossification in caries of different degree. Parietal ectopic ossification of the canal and cavity lumens in stages III and IV dental caries is regarded as a specific structural marker of pathological regeneration. The X-ray spectral analysis showed that the progress of carious process is paralleled by loss of mineral components. Laser-induced fluorescent study of tissues in extracted teeth showed 4 spectral bands corresponding to mineral and protein components of the tooth. The progress of carious process was associated with reduction of the fluorescence intensities of the spectral bands characteristic of dental collagen and mineral components.

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