Osteoporosis is a systemic disease that affects the skeleton, causing reduction of bone density and mass, resulting in destruction of bone microstructure and increased risk of bone fractures. Since osteoporosis is a disease affecting the elderly and the aging of the world’s population is constantly increasing, it is expected that the incidence of osteoporosis and its financial burden on the insurance systems will increase continuously and there is a need for more understanding this condition in order to prevent and/or treat it. At present, available drug therapy for osteoporosis primarily targets the inhibition of bone resorption and agents that promote bone mineralization, designed to slow disease progression. Safe and predictable pharmaceutical means to increase bone formation have been elusive. Stem cell therapy of osteoporosis, as a therapeutic strategy, offers the promise of an increase in osteoblast differentiation and thus reversing the shift towards bone resorption in osteoporosis. This review is focused on the current views regarding the implication of the stem cells in the cellular and physiologic mechanisms of osteoporosis and discusses data obtained from stem cell-based therapies of osteoporosis in experimental animal models and the possibility of their future application in clinical trials.

Obesity is a medical condition in which excess body fat may have a negative effect on health and lifestyle, and it is becoming an increasing problem within modern society. Leptin is the key protein that regulates body energy balance by inhibiting hunger, and it could potentially be used in treatment of obesity and overweight. Here, we applied our own Resonant Recognition Model, which is capable of analyzing the selectivity of any protein–receptor interaction on an example of leptin–leptin receptor. We have identified a specific characteristic parameter for leptin activity through the leptin receptor, and this parameter could be used in development of new treatments for obesity.

Classical pharmacological studies have shown that oestrogen dominance in humans and other animals can increase the responsiveness of the uterus to many locally acting peptides. Parathyroid hormone-related protein (PTHrP) has been shown to be expressed in the pregnant and non-pregnant rat uterus and exogenous PTHrP is known to relax uterine contraction in vitro. We investigated whether oestrogen dominance can influence the responsiveness of the uterine horn to PTHrP, and further studied the localization of PTHrP mRNA and protein in the rat uterine horn using in-situ hybridization and immunohistochemistry. Exogenous PTHrP(1-34) inhibited spontaneous and electrically induced contractions in uteri isolated from non-cycling rats. Pretreatment of non-cycling rats with oestradiol-17 beta increased uterine sensitivity to PTHrP: EC50 values for inhibition of spontaneous contractions by PTHrP were 0.33 nmol/l, 1.1 nmol/l, 2.6 nmol/l and 7800 nmol/l in uteri from animals treated for 2 days with oestradiol-17 beta alone, 2 days with oestradiol-17 beta + 1 day progesterone, 1 day with oestradiol-17 beta alone and in untreated rats respectively. Similar EC50 values were obtained for electrically stimulated uteri. In agreement with these findings, uterine horns from cycling rats in pro-oestrous and oestrous phases of the cycle showed a higher responsiveness to PTHrP(1-34) when compared with uterine horns taken from rats in metoestrus and dioestrus. PTHrP mRNA and protein were detected in the endometrial epithelium lining of the lumen and the endometrial glands, as well as in the myometrium of rats which were either pretreated for 2 days with oestradiol-17 beta or untreated. This study suggests that PTHrP may act in an autocrine and/or paracrine manner to modulate uterine motility and function.

Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being the predominant denominator for long-term complications. Epithelial and mesenchymal 2D cultures are highly utilized in vitro models for the preclinical evaluation of anti-inflammatory and antifibrotic therapies. More recently, human intestinal organoids (HIOs), a new 3D in vitro model derived from pluripotent stem cells, have the advantage to closely resemble the architecture of the intestinal mucosa. However, the appropriate timing for the study of inflammatory and fibrotic responses, during HIO development, has not been adequately investigated. We developed HIOs from the human embryonic stem cell line, H1, and examined the expression of mesenchymal markers during their maturation process. We also investigated the effect of inflammatory stimuli on the expression of fibrotic and immunological mediators. Serial evaluation of the expression of mesenchymal and extracellular matrix (ECM) markers revealed that HIOs have an adequately developed mesenchymal component, which gradually declines through culture passages. Specifically, CD90, collagen type I, collagen type III, and fibronectin were highly expressed in early passages but gradually diminished in late passages. The proinflammatory cytokines IL-1α and TNF-α induced the mRNA expression of fibronectin, collagen types I and III, tissue factor (TF), and alpha-smooth muscle actin (α-SMA) primarily in early passages. Similarly, HIOs elicited strong mRNA and protein mesenchymal (CXCL10) and epithelial (CXCL1, CCL2, CXCL8, and CCL20) chemokine responses in early but not late passages. In contrast, the epithelial tight junction components, CLDN1 and JAMA, responded to inflammatory stimulation independently of the culture passage. Our findings indicate that this HIO model contains a functional mesenchymal component, during early passages, and underline the significance of the mesenchymal cells’ fitness in inflammatory and fibrotic responses. Therefore, we propose that this model is suitable for the study of epithelial-mesenchymal interactions in early passages when the mesenchymal component is active.

The cystic fibrosis is genetic disease characterised by build-up of thick mucus in the lungs, which causes difficulties in breathing. It is caused by mutations in CFTR protein. Here, we utilised the Resonant Recognition Model (RRM), which proposes that proteins specific activity is characterised by specific frequencies (wavelengths) of electromagnetic radiation. Using the RRM approach, we have identified the electromagnetic frequency (wavelength) characterising the healthy CFTR proteins, while the amplitude at this frequency is diminishing in mutated CFTR proteins. Thus, the identified characteristic frequency (wavelength) for heathy CFTR proteins could be proposed to be critical for healthy functioning of CFTR proteins and for differentiating between healthy and malfunctioning CFTR proteins related to cystic fibrosis. In addition, using the RRM approach we achieved the possible explanation on how specific temperature of 27-28°C can restore the healthy function in mutated CFTR proteins.