One of the main aims in regenerative medicine is to find stem cells that are easy to obtain and are safe and efficient in either an autologous or allogenic host when transplanted. This review provides an overview of the potential use of the fetal annexes in regenerative medicine: we described the formation of the annexes, their immunological features, the new advances in the phenotypical characterization of fetal annexes-derived stem cells, the progressions obtained in the analysis of both their differentiative potential and their secretoma, and finally, the potential use of decellularized fetal membranes. Normally discarded as medical waste, the umbilical cord and perinatal tissue not only represent a rich source of stem cells but can also be used as a scaffold for regenerative medicine, providing a suitable environment for the growth and differentiation of stem cells.

Human perinatal stem cells (SCs) can be isolated from fetal annexes without ethical or safety limitations. They are generally considered multipotent; nevertheless, their biological characteristics are still not fully understood. The aim of this study was to investigate the pluripotency potential of human perinatal SCs as compared to human induced pluripotent stem cells (hiPSCs). Despite the low expression of the pluripotent factors NANOG, OCT4, SOX2, and C-KIT in perinatal SC, we observed minor differences in the promoters DNA-methylation profile of these genes with respect to hiPSCs; we also demonstrated that in perinatal SCs miR-145-5p had an inverse trend in comparison to these stemness markers, suggesting that NANOG, OCT4, and SOX2 were regulated at the post-transcriptional level. The reduced expression of stemness markers was also associated with shorter telomere lengths and shift of the oxidative metabolism between hiPSCs and fetal annex-derived cells. Our findings indicate the differentiation ability of perinatal SCs might not be restricted to the mesenchymal lineage due to an epigenetic barrier, but other regulatory mechanisms such as telomere shortening or metabolic changes might impair their differentiation potential and challenge their clinical application.

Cellular communication has a fundamental role in both human physiological and pathological states and various mechanisms are involved in the crosstalk between organs. Among these, microparticles (MPs) have an important involvement. MPs are a subtype of extracellular vesicles produced by a variety of cells following activation or apoptosis. They are normally present in physiological conditions, but their concentration varies in pathological states such as cardiovascular disease, diabetes mellitus, or cancer. Acute and chronic physical exercise are able to modify MPs amounts as well. Among various actions, exercise-responsive MPs affect angiogenesis, the process through which new blood vessels grow from pre-existing vessels. Usually, the neo vascular growth has functional role; but an aberrant neovascularization accompanies several oncogenic, ischemic, or inflammatory diseases. In addition, angiogenesis is one of the key adaptations to physical exercise and training. In the present review, we report evidence regarding the effect of various typologies of exercise on circulating MPs that are able to affect angiogenesis.

Degeneration of dopaminergic neurons represents the cause of many neurodegenerative diseases, with increasing incidence worldwide. The replacement of dead cells with new healthy ones may represent an appealing therapeutic approach to these pathologies, but currently, only pluripotent stem cells can generate dopaminergic neurons with high efficiency. However, with the use of these cells arises safety and/or ethical issues. Human mesenchymal stromal cells (hFM-MSCs) are perinatal stem cells that can be easily isolated from the amniochorionic membrane after delivery. Generally considered multipotent, their real differentiative potential is not completely elucidated. The aim of this study was to analyze their stemness characteristics and to evaluate whether they may overcome their mesenchymal fate, generating dopaminergic neurons. We demonstrated that hFM-MSCs expressed embryonal genes OCT4, NANOG, SOX2, KLF4, OVOL1, and ESG1, suggesting they have some features of pluripotency. Moreover, hFM-MSCs that underwent a dopaminergic differentiation protocol gradually increased the transcription of dopaminergic markers LMX1b, NURR1, PITX3, and DAT. We finally obtained a homogeneous population of cells resembling the morphology of primary midbrain dopaminergic neurons that expressed the functional dopaminergic markers TH, DAT, and Nurr1. In conclusion, our results suggested that hFM-MSCs retain the expression of pluripotency genes and are able to differentiate not only into mesodermal cells, but also into neuroectodermal dopaminergic neuron-like cells.

The 2022 asthma guidelines emphasise inhaled long-acting beta2-agonist formoterol as part of first treatment step, and therefore formoterol use among athletes will likely increase. However, prolonged supratherapeutic use of inhaled beta2-agonist impairs training outcomes in moderately-trained men. Here, we investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes.Fifty-one endurance-trained participants (31/20 male/female; maximal oxygen consumption(V′O2max): (mean±sd) 62±6/52±5 mLO2/min·kg−1) inhaled formoterol (n=26, 24 µg) or placebo (n=25) twice-daily for 6 weeks. At baseline and follow-up, we assessed V′O2maxand incremental exercise performance during a bike-ergometer ramp-test, body composition by Dual-Energy-X-ray-absorptiometry, muscle oxidative capacity by high-resolution mitochondrial-respirometry, enzymatic activity assays and immunoblotting, intravascular volumes by carbon-monoxide rebreathing, and cardiac left ventricle mass and function by echocardiography.Compared to placebo, formoterol increased lean body mass by 0.7 kg (95%CI: 0.2 to 1.2, treatment×trial p=0.022), but decreased V′O2max5% (treatment×trial p=0.013) and incremental exercise performance 3% (treatment×trial p<0.001). Formoterol also lowered muscle citrate synthase activity 15% (treatment×trial, p=0.063), mitochondrial complex-II and III content (treatment×trial p=0.028 and p=0.007, respectively), and maximal mitochondrial respiration through complex-I and I+II by 14% and 16% (treatment×trial p=0.044 and p=0.017, respectively). No apparent changes were observed in cardiac parameters and intravascular blood volumes. All effects were sex-independent.Our findings demonstrate that inhaled therapeutic doses of formoterol impair aerobic exercise capacity in endurance-trained individuals, which is in part related to impaired muscle mitochondrial oxidative capacity. Thus, if low-dose formoterol fails to control respiratory symptoms in asthmatic athletes, physicians may consider alternative treatment options.