Stem Cells and Cloning-Advances and Applications最新文献

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.

Introduction: Human decidua basalis mesenchymal stem cells (DBMSCs) are potential therapeutics for the medication to cure inflammatory diseases, like atherosclerosis. The current study investigates the capacity of DBMSCs to stay alive and function in a harmful inflammatory environment induced by high levels of lipopolysaccharide (LPS).

Methods: DBMSCs were exposed to different levels of LPS, and their viability and functional responses (proliferation, adhesion, and migration) were examined. Furthermore, DBMSCs' expression of 84 genes associated with their functional activities in the presence of LPS was investigated.

Results: Results indicated that LPS had no significant effect on DBMSCs' adhesion, migration, and proliferation (24 h and 72 h) (p > 0.05). However, DBMSCs' proliferation was significantly reduced at 10 µg/mL of LPS at 48 h (p < 0.05). In addition, inflammatory cytokines and receptors related to adhesion, proliferation, migration, and differentiation were significantly overexpressed when DBMSCs were treated with 10 µg/mL of LPS (p < 0.05).

Conclusion: These results indicated that DBMSCs maintained their functional activities (proliferation, adhesion, and migration) in the presence of LPS as there was no variation between the treated DBMSCs and the control group. This study will lay the foundation for future preclinical and clinical studies to confirm the appropriateness of DBMSCs as a potential medication to cure inflammatory diseases, like atherosclerosis.

Introduction: Intervertebral disc diseases (IVDD) represent the majority of neurological attendance and responsible for the most cases of paralysis in dogs. Treatments currently used do not show satisfactory results in patients with more severe and chronic neurological manifestations.

Methods: To promote nerve and muscular recovery, as well as improve quality of life, we aimed to create a double-blind test method, associating spinal decompression surgery and allogeneic transplantation of amniotic membrane-derived stem cells (AMSCs) in dogs with chronic IVDD. Cells were characterized as fetal mesenchymal cells and safe for application. Eight animals completed the experiment: stem cell applications were made in four animals that had previously undergone an unsuccessful surgical procedure ("SC group", n = 4); two animals were submitted to surgery, followed by applications of stem cells ("Surgery + SC", n = 2); two other animals were submitted to surgery, followed by the application of saline solution ("Surgery + placebo", n = 2). During the surgical procedure, a topical application was performed on the lesion and after fifteen and forty-five days another two applications were made via epidural. Animals were monitored biweekly and reassessed three months after surgery, by functional tests and magnetic resonance exams.

Results: Some animals presented significant neurological improvement, such as the recovery of nociception and ability to remain on station. Despite the need further studies, until the present moment, cell therapy has been feasible and has no harmful effects on animals.

Conclusion: The protocol of preclinical trial showed the association with decompressive surgery and cell transplantation in dogs with thoracolumbar IVDD proved feasible, and it was possible to observe neurological improvement after treatment. No tissue improvement through MRI was found. The double-blind test guaranteed reliability of the evaluations and results obtained that, even with a small sample size, generated satisfactory results for the animals and owners.

Introduction: Some laminoplasty procedures still have restenosis because of bony-bridging failure of the laminar hinge. The present study aimed to determine the effect of mesenchymal stem cell (MSC)-enriched scaffolds on vertebral regeneration after laminoplasty on the basis of the number of osteoblasts, matrix metalloproteinase-8 (MMP-8), and transforming growth factor-beta (TGF-β) levels.

Methods: Laminoplasty procedure using the Hirabayashi technique was conducted at the lumbar level in 32 rabbits that were divided into four and three groups of the control (C) and treatment groups, respectively, with different types of laminoplasty spacer (T1, autograft; T2, scaffold; and T3, scaffold with MSCs). Histopathological studies were conducted to calculate the number of osteoblasts and enzyme-linked immunosorbent assay tests to detect MMP-8 and TGF-β 4 weeks after the surgery.

Results: The results showed a significant decrease in MMP-8 level in the T3 group compared with that in the control group (p < 0.05). A significant difference exists between the average number of newly formed osteoblasts in the control group compared with that in the T3 group (p < 0.05) with a higher mean blood TGF-β level of all experimental groups compared with that of the control group (p = 0.58).

Conclusion: The significant decrease in MMP-8 levels, increase in TGF-β levels, and increased number of osteoblasts on MSC-seeded polylactic acid scaffolds could be useful to support the laminoplasty procedure to prevent restenosis because it was biocompatible and promoted the bone healing process.

Rationale: Loss of function mutations in DNA mismatch repair genes is the primary genetic defects in high-risk hereditary non-polyposis colon cancer (HNPCC). Cytotoxic chemotherapy and anti-inflammatory drugs are potential treatment options. These treatment options lead to systemic toxicity, acquired tumor resistance and the emergence of drug-resistant stem cells. A colonic epithelial cell culture model expressing the relevant genetic defects in chemo-resistant stem cells provides a relevant experimental system for HNPCC.

Objective: To develop a colonic epithelial cell culture system from a mouse model for HNPCC and to isolate and characterize drug-resistant stem cells.

Experimental models and biomarkers: The Mlh₁ ^[-/-]/Apc ^[-/-] Mlh₁/1638N COL-Cl₁ cells is a mouse model for HNPCC, and the 5-fluoro-uracil resistant (5-FU-R) phenotype represents a model for the drug-resistant stem cells. Tumor spheroid formation, and the expression of CD44, CD133 and c-Myc represent stem cell markers.

Results: The HNPCC model exhibits aneuploidy, hyper-proliferation, accelerated cell cycle progression and downregulated cellular apoptosis. Long-term exposure to 5-FU selects for the drug-resistant phenotype. These resistant cells exhibit increased formation of tumor spheroids and upregulated expression of cancer stem cell markers CD44, CD133 and c-Myc.

Conclusion: In the present study, a stem cell model for HNPCC was validated and offered a novel experimental approach to test stem cell-targeted alternatives to drug-resistant therapy.

Purpose: Comparative reanalysis of single-cell transcriptomics data to gain useful novel insights into cancer stem cells (CSCs), which are a rare subset of cells within tumors, characterized by their capability to self-renew and differentiate, and their role in tumorigenicity.

Patients and methods: This project utilized publically available liver single-cell RNA-seq datasets of liver cancer and liver progenitor cell types to demonstrate how shared large amounts of data can generate new and valuable information. The data were analyzed using EdgeR differential expression analysis, with focus on a set of 34 known stemness markers.

Results: We showed that the expression of stemness markers SOX9, KRT19, KRT7, and CD24, and Yamanaka factors Oct4 and SOX2 in CSCs was significantly elevated relative to progenitor cell types, potentially explaining their increased differentiation and replication potential.

Conclusion: These results help to further document the complementary expression changes that give CSCs their distinct phenotypic profile. Our findings have potential significance to advance our knowledge of the important genes relevant to CSCs.

There is numerous evidence for the presence of stem cells, which is important for the treatment of a wide variety of disease conditions. Stem cells have a great therapeutic effect on different degenerative diseases through the development of specialized cells. Embryonic stem (ES) cells are derived from preimplantation embryos, which have a natural karyotype. This cell has the capacity of proliferation indefinitely and undifferentiated. Stem cells are very crucial for the treatment of different chronic and degenerative diseases. For instance, stem cell clinical trials have been done for ischemic heart disease. Also, the olfactory cells for spinal cord lesions and human fetal pancreatic cells for diabetes mellitus are the other clinical importance of stem cell therapy. Extracellular matrix (ECM) and other environmental factors influence the fate and activity of stem cells.

[This corrects the article DOI: 10.2147/SCCAA.S253108.].

Introduction: Osteoarthritis causes a progressive deterioration to the protective cartilage between the joints leading to chronic pain and disability. This review focuses on the intrinsic potential of MSCs to stabilize and repair the cartilage tissue of the knee joint in knee osteoarthritis (KOA) patients.

Methods: An online search through the PubMed database was conducted, limiting the search to the English language and human clinical trials within the past 5 years. Twenty-one clinical trials passed the inclusion criteria. Combined, those trials involved the participation of 589 patients where the progress of the treatments was monitored between a 4-month to 7-years period. The cartilage volume and defects were observed through an MRI to provide an objective assessment. While the pain and knee function were monitored using KOOS, VAS, and WOMAC scoring scales providing a subjective assessment.

Results: MRI scans obtained from clinical trials demonstrate a slowed progression of cartilage degeneration and early signs of cartilage regeneration in KOA patients at the 12-month follow-up period. No major adverse effects were observed post-intervention. The overall KOOS, WOMAC, and VAS scores in patients receiving MSC treatment were reduced, suggesting subjective improvements in knee function and pain reduction when compared to patients in the placebo group.

Conclusion: The use of MSC therapy is a valid form of treatment for KOA as it targets the disease itself rather than the symptoms. We found MSC therapy in KOA patients to be safe, effective, and feasible in its execution.