Autologous Cell Therapies for Bone Tissue Regeneration

The healing potential of bone is sufficient to restore simple fractures, which are generally treated by standard conservative or surgical therapy. However, in some cases, reparative osteogenesis does not result in structural and functional recovery of the bone. Extended bone defects following trauma or cancer resection or non-unions of fractures may require more sophisticated treatment. In these cases, bone grafting procedures, segmental bone transport, distraction osteogenesis or biomaterials are applied for reconstruction

A “Crossomics” Study Analysing Variability of Different Components in Peripheral Blood of Healthy Caucasoid Individuals

Background: Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable. Methodology/Principal Findings: To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics'' analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4(+)T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset. Conclusions/Significance: Our study shows that the intra- individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective

Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

The COVID-19 pandemic has significantly impacted the way of life worldwide and continues to bring high mortality rates to at-risk groups. Patients who develop severe COVID-19 pneumonia, often complicated with ARDS, are left with limited treatment options with no targeted therapy currently available. One of the features of COVID-19 is an overaggressive immune reaction that leads to multiorgan failure. Mesenchymal stromal cell (MSC) treatment has been in development for various clinical indications for over a decade, with a safe side effect profile and promising results in preclinical and clinical trials. Therefore, the use of MSCs in COVID-19-induced respiratory failure and ARDS was a logical step in order to find a potential treatment option for the most severe patients. In this review, the main characteristics of MSCs, their proposed mechanism of action in COVID-19 treatment and the effect of this therapy in published case reports and clinical trials are discussed

The problem of calcified ascending aorta during aortocoronary bypass

Heavily calcified ascending aorta significantly increased morbidity and lethality during open-heart surgery. Cannulation and clamping (partial or total) of severely atherosclerotic ascending aorta can easily cause damage and rupture of aortic wall, with consequential distal (often fatal) embolization with atheromatous debris (brain, myocardium). From June 1998. until June 2000, 11 of 2 136 (0.5%) patients who underwent coronary artery bypass grafting were with the severe atheromatous ascending aorta. The site of cannulation was in the aortic arch in three patients (aorta was occluded with Foley catheter in one case, and single clamp technique was used in the other two cases). The femoral artery was the cannulation site in other five cases. Profound hypothermia, ventricular fibrillation, and circulatory arrest, with no cross-clamping or cardioplegia, were used in three patients. Two patients were operated on with extracorporeal circulation, one in normothermia, on the beating heart, the other in moderate hypothermia, on fibrillating heart. In three patients myocardial revascularization was performed on the beating heart, in normothermia, without extracorporeal circulation. Postoperative course was uneventful in all 11 patients. Neither atheroembolism in the peripheral organs, nor atheroembolism of the extramities occurred. The proposed surgical approaches have the potential to reduce the prevalence of stroke and systemic embolization associated with coronary artery bypass grafting in patients with heavily calcified ascending aorta. This result was achieved due to the applied modifications of standard cardiosurgical technique

Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with a Prognostic Impact on Survival and Those of Viral Origin

<div><p>Background</p><p>Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis in spite of a plethora of established diagnostic and prognostic biomarkers and treatment modalities. Therefore, the current goal is the detection of novel biomarkers, possibly detectable in the blood of GBM patients that may enable an early diagnosis and are potential therapeutic targets, leading to more efficient interventions.</p><p>Experimental Procedures</p><p>MicroRNA profiling of 734 human and human-associated viral miRNAs was performed on blood plasma samples from 16 healthy individuals and 16 patients with GBM, using the nCounter miRNA Expression Assay Kits.</p><p>Results</p><p>We identified 19 miRNAs with significantly different plasma levels in GBM patients, compared to the healthy individuals group with the difference limited by a factor of 2. Additionally, 11 viral miRNAs were found differentially expressed in plasma of GBM patients and 24 miRNA levels significantly correlated with the patients’ survival. Moreover, the overlap between the group of candidate miRNAs for diagnostic biomarkers and the group of miRNAs associated with survival, consisted of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa miR 592 and hsa miR 514a 3p have not been previously described in GBM and represent novel candidates for selective biomarkers. The possible signalling, induced by the revealed miRNAs is discussed, including those of viral origin, and in particular those related to the impaired immune response in the progression of GBM.</p><p>Conclusion</p><p>The GBM burden is reflected in the alteration of the plasma miRNAs pattern, including viral miRNAs, representing the potential for future clinical application. Therefore proposed biomarker candidate miRNAs should be validated in a larger study of an independent cohort of patients.</p></div

Hierarchical clusters of rules for the validated targets of miRNAs detected in the plasma samples of GPs.

<p>Hierarchical clustering of the top 100 statistically significant rules (p≤0.05) is presented. The SegMine rules were derived from genes, representing validated targets of the GBM-related plasma miRNAs. Euclidian distance and Ward’s linkage criteria were used to compute the hierarchy.</p

Genes most frequently targeted by miRNAs, correlated to the presence of GBM or patient survival.

<p>The presented genes are validated targets of miRNAs differentially expressed in the plasma samples of GPs and the members of the HIo subgroup and/or correlated to patient survival according to the results of analyses of this study, obtained by using the miRTarBase [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125791#pone.0125791.ref032" target="_blank">32</a>]. <i>VEGFA</i>—vascular endothelial growth factor A, <i>HSPA1B</i>—heat shock 70kDa protein 1B, <i>ACTB</i>—actin beta, <i>HSP90AA1</i>—heat shock protein 90kDa alpha (cytosolic), class A member 1, <i>IGF1R</i>—insulin-like growth factor 1 receptor, <i>CCND1</i>—cyclin D1, <i>PTEN</i>—phosphatase and tensin homolog, <i>BCL2</i>—B-cell CLL/lymphoma 2, <i>CCNE1</i>—cyclin E1, <i>CDK4</i>—cyclin-dependent kinase 4, <i>PPIA</i>—peptidylprolyl isomerase A (cyclophilin A), <i>TUBA1B</i>—tubulin, alpha 1b, <i>WEE1</i>—WEE1 G2 checkpoint kinase, <i>CCND2</i>—cyclin D2, <i>CDK2</i>—cyclin-dependent kinase 2, <i>CDK6</i>—cyclin-dependent kinase 6, <i>BIRC5</i>—baculoviral IAP repeat containing 5, <i>EP300</i>—E1A binding protein p300, <i>RRM2</i>—ribonucleotide reductase M2.</p

Log2 expression values of 11 viral miRNAs, differentially expressed in the GP and HIo plasma samples.

<p>The bars represent the mean values and x each analysed plasma sample.</p