Abstract Despite extensive studies, Duchenne muscular dystrophy, a neuromuscular disorder caused by the lack of dystrophin, a key muscle structural protein, remains an incurable disease. One of the potential treatment options currently being investigated is cell therapy, although it has not yet been clinically established. Several strategies, including muscle satellite cells, mesoangioblasts (vessel-associated multipotent stem cells), and induced pluripotent stem cell (iPSC)-derived muscle cells, have emerged as tools for restoring dystrophin expression and regenerating damaged muscle tissue. Nevertheless, each of these approaches faces significant limitations, including poor cell engraftment, low delivery efficiency, and the risk of immune rejection. Furthermore, long-term safety, the possibility of tumorigenicity, and off-target effects must be rigorously evaluated. Importantly, the latter technology, utilizing cardiomyocytes differentiated from iPSC, holds the potential for addressing cardiomyopathy, the major cause of death of DMD patients. At the same time, several interventions using cells with claimed stem cell potential have emerged, raising both scientific and ethical concerns. This review summarizes recent advancements in the development of cell therapies for DMD, highlighting promising progress while critically analysing questionable approaches.
HO-1 (haem oxygenase-1) is a ubiquitously expressed inducible enzyme degrading haem to CO, biliverdin and Fe2+. Its activation reduces oxidative stress in cells and inhibits inflammation, both due to removal of haem and because of the biological activity of HO-1 products. CO may act similarly to NO, activating soluble guanylate cyclase and elevating cGMP production. It inhibits platelet aggregation, reduces leucocyte adhesion, decreases apoptosis and lowers the production of some pro-inflammatory cytokines. Biliverdin is converted into bilirubin by biliverdin reductase, and both compounds are potent antioxidants, free radical scavengers and inhibitors of the complement cascade. Iron ions can be potentially toxic, increasing the generation of hydroxyl radicals, but simultaneous induction of ferritin and activation of the Fe-ATPase iron transporter protects cells from oxidative stress. Importantly, basal and induced expression of HO-1 is very variable in the human population because of the highly polymorphic (GT)n fragment in the promoter, which may have clinical relevance. The recognized roles of HO-1 are far beyond cytoprotection. The enzyme is important in the regulation of cell proliferation, differentiation and apoptosis. Its activity improves neovascularization, attenuates inflammation and modulates the immune response, thereby influencing carcinogenesis, wound healing, transplant survival and the progression of cardiovascular diseases. Recent results indicate that HO-1 may also act through the regulation of microRNAs, which suggests a much broader involvement of HO-1 in the modulation of cell functions and offers a potential explanation for some well-known activities whose mechanism has hitherto been unclear.
Angiogenesis involves the formation of new blood vessels and is critical for fundamental events such as development and repair after injury. Perturbances in angiogenesis contribute to the pathogenesis of diverse clinical conditions including cancer, complications of diabetes mellitus, ischemia/reperfusion injury of the heart and other organs, and preeclampsia, as well as a number of inflammatory disorders. Recent work has identified heme oxygenase-1 and its gaseous product, carbon monoxide, to possess potent proangiogenic properties in addition to well-recognized antiinflammatory, antioxidant, and antiapoptotic effects. Angiogenic factors, such as vascular endothelial growth factor and stromal cell–derived factor-1, mediate their proangiogenic effects through induction of heme oxygenase-1, making it an attractive target for therapeutic intervention. This review will provide an overview of the role of heme oxygenase-1 and carbon monoxide in angiogenesis.
Chronic myelogenous leukemia is characterized by an abnormal 22nd chromosome known as a Philadelphia chromosome, which can be detected in 95% of patients with CML. Molecular equivalent of this aberration is a BCR-ABL translocation resulting in chimeric gene formation. A BCR-ABL chimeric gene plays a key role in the hematopoietic cells proliferation regulation. RT-PCR can be used in diagnosis of CML, to detect chimeric BCR-ABL gene, and to reveal the type of translocation what could have prognostic importance, and in monitoring of minimal residual disease, confirming the eradication of pathological cells clone after treatment and identifying the group of patients with best prognosis and best overall survival. RT-PCR in monitoring of minimal residual disease after allo- or autologous hemopoietic cells transplantation can early reveal relapse of the disease. Detection of molecular relapse is an important prognostic factor and may implicate induction of treatment which should prevent haematological relapse of the disease.
