Stem Cells and Cloning-Advances and Applications最新文献

Cancer continues to rank among the world's leading causes of mortality despite advancements in treatment. Cancer stem cells, which can self-renew, are present in low abundance and contribute significantly to tumor recurrence, tumorigenicity, and drug resistance to various therapies. The drug resistance observed in cancer stem cells is attributed to several factors, such as cellular quiescence, dormancy, elevated aldehyde dehydrogenase activity, apoptosis evasion mechanisms, high expression of drug efflux pumps, protective vascular niche, enhanced DNA damage response, scavenging of reactive oxygen species, hypoxic stability, and stemness-related signaling pathways. Multiple studies have shown that mitochondria play a pivotal role in conferring drug resistance to cancer stem cells, through mitochondrial biogenesis, metabolism, and dynamics. A better understanding of how mitochondria contribute to tumorigenesis, heterogeneity, and drug resistance could lead to the development of innovative cancer treatments.

Introduction: Cells collected from Wharton's jelly are a rich source of mesenchymal stem cells. They can be easily obtained and grown using the adhesive method. They produce many types of proteins, including VEGF. Their role is to participate in angiogenesis, vasodilation, stimulation of cells to migrate, and chemotactic activity. The aim of this study was to evaluate expression of genes from the vascular endothelial growth factor family: VEGFA, VEGFB and VEGFC in MSC and the analysis of dependence of the expression of the studied genes on clinical factors related to the course of pregnancy and childbirth, and health of mother and child.

Material and methods: The research material was an umbilical cord obtained from 40 patients hospitalized in the Department of Obstetrics and Pathology of Pregnancy of the Independent Public Clinical Hospital No.1 in Lublin. The age of the women was 21-46, all gave birth by cesarean section. Some of the patients suffered from hypertension and hypothyroidism. Material collected from patients immediately after delivery was subjected to enzymatic digestion with type I collagenase. The isolated cells were then cultured in adherent conditions, and then gene expression was assessed using qPCR and the immunophenotype of the cells was assessed cytometrically.

Results: Conducted studies have shown significant differences in expression of VEGF family genes depending on clinical condition of mother and child. Significant differences in VEGF-family gene expression level in umbilical cord MSC collected from women with hypothyroidism, hypertension, time of labor and birth weight of the baby were shown.

Conclusion: Probably due to hypoxia (caused, for example, by hypothyroidism or hypertension), the MSCs found in the umbilical cord may react with an increased expression of VEGF and a compensatory increase in the amount of secreted factor, the aim of which is, i.a., vasodilation and increase of blood supply to the fetus through the umbilical vessels.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with no known cure, characterized by the formation of scar tissue in the lungs, leading to respiratory failure. Although the exact cause of IPF remains unclear, the condition is thought to result from a combination of genetic and environmental factors. One of the most widely used animal models to study IPF is the bleomycin-induced lung injury model in mice. In this model, the administration of the chemotherapeutic agent bleomycin causes pulmonary inflammation and fibrosis, which closely mimics the pathological features of human IPF. Numerous recent investigations have explored the functions of various categories of stem cells in the healing process of lung injury induced by bleomycin in mice, documenting the beneficial effects and challenges of this approach. Differentiation of stem cells into various cell types and their ability to modulate tissue microenvironment is an emerging aspect of the regenerative therapies. This review article aims to provide a comprehensive overview of the role of stem cells in repairing bleomycin-induced lung injury. It delves into the mechanisms through which various types of stem cells, including mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, and lung resident stem cells, exert their therapeutic effects in this specific model. We have also discussed the unique set of intermediate markers and signaling factors that can influence the proliferation and differentiation of alveolar epithelial cells both during lung repair and homeostasis. Finally, we highlight the challenges and opportunities associated with translating stem cell therapy to the clinic for IPF patients. The novelty and implications of this review extend beyond the understanding of the potential of stem cells in treating IPF to the broader field of regenerative medicine. We believe that the review paves the way for further advancements in stem cell therapies, offering hope for patients suffering from this debilitating and currently incurable disease.

Background: Umbilical cord mesenchymal stem cells (UC-MSCs)-derived secretome is currently used in regenerative therapy. MSCs are believed to secrete a wide spectrum of bioactive molecules which give paracrine effects in immunomodulation and regenerative capacities. One group that was found in secretome is interleukins (ILs), a cytokine that plays an essential role in the process of proliferation, differentiation, maturation, migration, and adhesion of immune cells. However, as there are many types of ILs, the profile of ILs in the UC-MSCs-derived secretome has been limitedly reported. Therefore, in this study, we would like to profile and detect the interleukin concentration secreted by UC-MSCs.

Methods: UC-MSCs-derived secretome was collected from UC-MSCs passage 5 after 24- and 48-hour incubation (n=9). Secretome was filtered using 0.2 µm and stored at -80°C for further detection. All samples were normalized before the interleukin (IL-2, IL-4, IL-6, IL-9, IL-10, IL-12, IL-17A) detection using a MACSPlex Cytokine Kit.

Results: The IL-6 has the highest concentration among other interleukins in both groups and increases significantly (p<0.003) after incubation for 48 hours. The pro-inflammatory factors are decreasing while anti-inflammatory factors are increasing after 48-hour incubation.

Discussion: Our studies show that the UC-MSCs secrete pro- and anti-inflammatory interleukins. The concentration of anti-inflammatory interleukins shows to be increasing, while the pro-inflammatory interleukins are decreasing within the longer incubation time, but this not be applicable for IL-10 and IL-6. IL-6 has the highest concentration among other ILs. These results may provide important clues regarding when is the right time for secretome to be used in therapy patients, because all the molecules in the secretome can lead to many clinical manifestations.

Introduction: Mesenchymal stem cells (MSCs) have been postulated by a number of authors to be the precursor cells of fibroblasts and myofibroblasts in keloids. They have been seen as a regenerative pool that ensures a steady supply of cells. The objective of our study was to determine MSCs in keloids and normal skin as a determinant of keloid recurrence.

Methods: This was a longitudinal prospective study in which patients with keloid excisions of their specimens analyzed for MSC. A control group of patients matched for age, sex, and body-mass index (BMI) with no history of keloids admitted for elective surgical procedures had their skin samples taken and also analyzed for MSCs. Data collected were analyzed and compared using Student's t, x ², and Fisher's exact t tests.

Results: A total of 61 patients with keloids and a control group of 32 patients were recruited. The male:female ratio was 1:2 and mean age 29.5 and 29.7 years for keloids and controls, respectively. Patients with recurrent keloids had a mean density of 841.4 MSCs/g compared to 578 MSCs/g of tissue for those with no recurrence and 580 MSCs/g for patients with normal skin. Recurrent keloids had a significantly higher percentage of MSCs than those without.

Conclusion: Keloids compared to normal skin had a higher percentage of MSCs, with recurrent keloids demonstrating an even higher count, a possible indicator that MSCs might correlate with severity of keloid disease and recurrence.

Introduction: Stroke is a leading cause of death and disability worldwide. The disease is caused by reduced blood flow into the brain resulting in the sudden death of neurons. Limited spontaneous recovery might occur after stroke or brain injury, stem cell-based therapies have been used to promote these processes as there are no drugs currently on the market to promote brain recovery or neurogenesis. Adult stem cells (ASCs) have shown the ability of differentiation and regeneration and are well studied in literature. ASCs have also demonstrated safety in clinical application and, therefore, are currently being investigated as a promising alternative intervention for the treatment of stroke.

Methods: Eleven studies have been systematically selected and reviewed to determine if autologous adult stem cells are effective in the treatment of stroke. Collectively, 368 patients were enrolled across the 11 trials, out of which 195 received stem cell transplantation and 173 served as control. Using data collected from the clinical outcomes, a broad comparison and a meta-analysis were conducted by comparing studies that followed a similar study design.

Results: Improvement in patients' clinical outcomes was observed. However, the overall results showed no clinical significance in patients transplanted with stem cells than the control population.

Conclusion: Most of the trials were early phase studies that focused on safety rather than efficacy. Stem cells have demonstrated breakthrough results in the field of regenerative medicine. Therefore, study design could be improved in the future by enrolling a larger patient population and focusing more on localized delivery rather than intravenous transplantation. Trials should also introduce a more standardized method of analyzing and reporting clinical outcomes to achieve a better comparable outcome and possibly recognize the full potential that these cells have to offer.

Coronavirus-2019 disease is a newly diagnosed infectious disease, which is caused by the severe acute respiratory syndrome corona virus-2. It spreads quickly and has become a major public health problem throughout the world. When the viral structural spike protein binds to the angiotensin-converting enzyme-2 receptor of the host cell membrane, the virus enters into host cells. The virus primarily affects lung epithelial cells or other target cells that express angiotensin-converting enzyme-2 receptors in COVID-19 patients. Chemokines released by the host cells stimulate the recruitment of different immune cells. A cytokine storm occurs when a high amount of pro-inflammatory cytokines are produced as a result of the accumulation of immune cells. In COVID-19 patients, cytokine storms are the leading cause of severe acute respiratory distress syndrome. Mesenchymal stem cells are multipotent and self-renewing adult stem cells, which are obtained from a variety of tissues including bone marrow, adipose tissue, Warthon's jelly tissue, and amniotic fluid. Mesenchymal stem cells primarily exert their important therapeutic effects through 2 mechanisms: immunoregulatory effects and differentiation capacity. Mesenchymal stem cells can release several cytokines via paracrine mechanism or by direct interaction with white blood cells such as natural killer cells, T-lymphocytes, B-lymphocytes, natural killer cells, and macrophages, resulting in immune system regulation. Mesenchymal stem cells may help to restore the lung microenvironment, preserve alveolar epithelial cells, prevent lung fibrosis, and treat pulmonary dysfunction that is caused by COVID-19 associated pneumonia. Mesenchymal stem cells therapy may suppress aggressive inflammatory reactions and increase endogenous restoration by improving the pulmonary microenvironment. Furthermore, clinical evidence suggests that intravenous injection of mesenchymal stem cells may radically reduce lung tissue damage in COVID-19 patients. With the advancement of research involving mesenchymal stem cells for the treatment of COVID-19, mesenchymal stem cells therapy may be the main strategy for reducing the recent pandemic.