Stem Cells International最新文献

Objectives: The goal of this study was to examine the existing evidence from randomized controlled trials (RCTs) on the efficacy of cell treatment in alveolar cleft (AC). Design: An electronic search was done for studies published between January 2000 and May 2024 in the PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Primary outcomes were the radiographic assessment of bone graft volume, and the secondary outcome of interest was the number of complications after surgery. A random-effects model and fix-effect model were employed to pool effect sizes, and heterogeneity was assessed using I ² statistics. Results: Four RCTs, comprising 51 patients, were included in the systematic review and meta-analysis. No statistically significant difference in bone volume (MD [mean difference] -0.82; 95% CI [-3.59, 5.24]; p=0.71) when using cells therapy to repair AC compared to using autologous iliac crest bone graft repair AC. Also, there is no difference in postoperative complications (MD 0.66; 95% CI [0.13, 3.39]; p=0.62) between the two groups. In this meta-analysis, cells therapy on alveolar bone grafting produced results comparable to autologous bone grafting in new bone formation rate and complications. Conclusions: In conclusion, this systematic review and meta-analysis appear to indicate no disadvantage to utilizing cell therapy in AC reconstruction versus autologous bone grafting in terms of bone volume or complications.

Background: Ovarian cancer (OC) stands as the leading cause of cancer-related deaths among women, globally, owing to metastasis and acquired chemoresistance. Cancer stem cells (CSCs) are accountable for tumor initiation and exhibit resistance to chemotherapy and radiotherapy. Identifying stemness-related biomarkers that can aid in the stratification of risk and the response to chemotherapy for OC is feasible and critical. Methods: Gene expression and clinical data of patients with OC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Four thousand three hundred seventeen stemness-related genes (SRGs) were acquired from the StemChecker database. TCGA was used as the training dataset, while GSE30161 served as validation dataset. Univariate Cox regression analysis was used to identify overall survival (OS)-related SRGs, and multivariate Cox regression analysis and random survival forest analysis were used for generating stemness-relevant prognostic model. Kaplan-Meier plots were used to visualize survival functions. Receiver operating characteristic (ROC) curves were used to assess the prognostic predictive ability of SRG-based features. Associations between signature score, tumor immune phenotype, and response to chemotherapy were analyzed via TIMER 2.0 and oncoPredict R package, respectively. A cohort of Shanghai Cancer Center was employed to verify the predictive robustness of the signature with respect to chemotherapy response. Results: Seven SRGs (actin-binding Rho activating C-terminal like (ABRACL), growth factor receptor bound protein 7 (GRB7), Lin-28 homolog B (LIN28B), lipolysis stimulated lipoprotein receptor (LSR), neuromedin U (NMU), Solute Carrier Family 4 Member 11 (SLC4A11), and thymocyte selection associated family member 2 (THEMIS2)) were found to have excellent predictive potential for patient survival. Patients in the high stemness risk group presented a poorer prognosis (p  < 0.0001), and patients with lower stemness scores were more likely to benefit from chemotherapy. Several tumorigenesis pathways, such as mitotic spindle and glycolysis, were enriched in the high stemness risk group. Tumor with high-risk scores tended to be in a status of relatively high tumor infiltration of CD4+ T cells, neutrophils, and macrophages, while tumor with low-risk scores tended to be in a status of relatively high tumor infiltration of CD8+ T cells. Conclusions: The stemness-relevant prognostic gene signature has the potential to serve as a clinically helpful biomarker for guiding the management of OC patients.

Acute kidney injury (AKI) is a rapid decline in renal function caused by ischemia/reperfusion (I/R), renal toxic injury, and sepsis. While the precise molecular mechanisms underlying AKI are still under investigation, current therapeutic approaches remain insufficient. In recent years, there has been growing evidence that mesenchymal stem cells (MSCs) have great potential in accelerating renal repair after AKI in various preclinical models, while there has been extensive research on extracellular vesicles (EVs) as therapeutic mediators in AKI models, and they are considered to be superior to MSCs as new regenerative therapies. EVs are nanoparticles secreted by various types of cells under physiological and pathological conditions. EVs derived from various sources possess biomarker potential and play crucial roles in mediating cellular communication between kidney cells and other tissue cells by transmitting signal molecules. These vesicles play a direct and indirect role in regulating the pathophysiological mechanisms of AKI and contribute to the occurrence, development, treatment, and repair of AKI. In this review, we briefly outline the essential characteristics of EVs, focus on the multiple molecular mechanisms currently involved in the protection of EVs against different types of AKI, and further discuss the potential targets of EVs from different sources in the treatment of AKI. Finally, we summarized the deficiencies in the production and treatment of EVs and the current strategies for improvement.

Tissue repair following skin injury is a complex process that encompasses hemostasis, inflammation, tissue cell proliferation, and structural remodeling. Mesenchymal stem cells (MSCs) are derived from the mesodermal layer of tissues and possess multidirectional differentiation potential and self-renewal capabilities. MSCs from various sources, including the bone marrow, adipose tissue, dental pulp, umbilical cord, and amniotic membrane, have demonstrated effectiveness in promoting skin injury repair. They aid in this process by fostering the formation of new blood vessels in damaged tissues, self-renewal, or transdifferentiation into skin or sweat gland cells. Moreover, MSCs promote the proliferation and migration of skin cells, reduce wound inflammation, and restore the extracellular matrix through paracrine secretion. In this paper, we review recent findings regarding MSCs and their role in burn wound repair. Additionally, we explore the potential of combining MSCs with various biomaterials for treating burn wounds and analyze clinical cases wherein MSCs were administered to patients, offering insights into ongoing research on MSC-based therapies for skin injuries.

Objective: The traumatic pancreatitis (TP) has an alarmingly high mortality rate. Our previous research has demonstrated that human umbilical cord mesenchymal stem cells-derived exosomes (hucMSC-Exs) could treat TP by inhibiting acinar cell apoptosis. Accordingly, the objective of this study is to unravel the intricate mechanism behind the repair of pancreatic injury in TP rats. Methods: A gene interaction network of miRNA was constructed based on the Gene Expression Omnibus (GEO) database (GSE 159814). Our investigation was divided into two groups, and appropriate controls were implemented for each group. The expression levels of inflammatory factors in each group were detected, along with the pathological damage of pancreatic tissue, the percentage of apoptotic cells, and key mRNA and protein expression levels. Results: The miRNA-mRNA gene interaction network suggests that hsa-miR-21-5p/phosphatase and tensin homolog (PTEN) are positioned at the core of this interaction network. Enzyme-linked immunosorbent assay (ELISA) and histological examination (HE) results suggest that pancreatic damage increased in the miR-21 inhibitor and EXW groups, whereas it decreased in the miR-21 activator and EXC groups compared to the EX group. PCR, western blot (WB), and TdT-mediated dUTP Nick-End Labeling (TUNEL) results indicate that hucMSC-Ex carrying hsa-miR-21-5p suppresses excessive activation of PTEN by phosphoinositide 3-kinase (PI3K), exerting therapeutic effects. Conclusion: This study has discovered that hucMSC-Ex effectively inhibits the translation of PTEN via the transported hsa-miR-21-5p, consequently affecting the PI3K/serine-threonine kinase (AKT) signaling pathway. This results in reduced inflammation and inhibition of acinar cell apoptosis by regulating pancreatic enzyme leakage, thereby providing a therapeutic effect on TP.

Numerous researches have demonstrated the therapeutic potential of adipose-derived stem cell exosomes (ADSC-Exos) in promoting wound healing. In this study, we aimed to investigate the impact of ADSC-Exos on diabetic wound fibroblasts and elucidate its possible mechanisms. CCK-8, Edu, cell scratch, and Transwell tests were used to evaluate the function of ADSC-Exos on rat skin fibroblasts (RSFs) in high-glucose (HG) medium. The targeting effect of ADSC-Exo-derived microRNA (miRNA) and TGF-β1 was assessed using bioinformatic analysis and then confirmed with western blot and dual luciferase reporter assays. ADSC-Exos, miR-204-5p mimic, and anti-miR-204-5p mimic were used to stimulate RSFs, and the levels of TGF-β1/Smad pathway were analyzed by western blot. In vivo, digital photo and tissue section staining were used to evaluate the therapeutic effect of ADSC-Exos on diabetic wounds. The data showed that ADSC-Exos enhance the proliferation and migration of fibroblasts under HG conditions, reduce excessive myofibroblast differentiation and collagen deposition, and promote scarless healing of diabetic wounds. Additionally, miR-204-5p in ADSC-Exos targets TGF-β1 to inhibit p-Smad2/3, Col I, and alpha-smooth muscle actin (α-SMA), thereby reducing fibrosis. These findings suggest that ADSC-Exos have potential prospects for promoting diabetic wound healing.

The skeleton is an important organ in the human body. Bone defects caused by trauma, inflammation, tumors, and other reasons can impact the quality of life of patients. Although the skeleton has a certain ability to repair itself, the current most effective method is still autologous bone transplantation due to factors such as blood supply and defect size. Modern medicine is attempting to overcome these limitations through cell therapy, with mesenchymal stem cells (MSCs) playing a crucial role. MSCs can be extracted from different tissues, and their differentiation potential varies depending on the source. Various cells and cell secretions can influence this process. This article, based on previous research, reviews the effects of macrophages, endothelial cells (ECs), nerve cells, periodontal cells, and even some bacteria on MSC osteogenic differentiation, aiming to provide a reference for multicell coculture strategies related to osteogenesis.

Since their discovery, human induced pluripotent stem cells (hiPSCs) have been instrumental in biomedical research, particularly in the fields of disease modelling, drug screening and regenerative therapies. Their use has significantly increased over recent years driven by the ability of hiPSCs to provide differentiated cell models without requiring embryonic stem cells. Furthermore, the transition from integrating to non-integrating reprogramming methodologies has contributed to the increase in utilisation. This shift minimises the risk of genomic alterations, enhancing the safety and reliability of hiPSCs. However, the factors that contribute to reprogramming success are still not well understood. In this study, we conducted a comparative analysis of the most prevalent non-integrating reprogramming methods across a range of starting source materials to assess their impact on reprogramming success rates. We found that while source material does not significantly impact success rates, the Sendai virus reprogramming method yields significantly higher success rates relative to the episomal reprogramming method. Our findings offer important insights from a biobanking perspective, for which long-term reliability, integrity and reproducibility of hiPSCs are crucial.

Introduction: Renal dysfunction due to ischemia-reperfusion injury (IRI) is a common problem after kidney transplantation. In recent years, studies on animal models have shown that exosomes derived from mesenchymal stem cells (MSC-Exo) play an important role in treating acute kidney injury (AKI) and promoting tissue repair. The microneedle patch provides a noninvasive and targeted delivery system for exosomes. The purpose of this innovative approach is to combine MSC-Exo with microneedle patches. Method: Exosomes were isolated from MSCs, characterized, and placed in the prepared microneedle patch. Then this construct was applied to the IRI mice model. After 7 days, the gene expression of miR-34a and its targets B-cell lymphoma-2 (BCL-2) and BCL-2-associated X (BAX), along with reactive oxygen species (ROS) and lipid peroxidation (LPO) production, was investigated. Additionally, renoprotection was evaluated for measuring blood urea nitrogen (BUN) and creatinine (Cr) and histopathology detection. Results: After using microneedle patches containing exosomes, the reduction of miR-34a and BAX and enhancement of BCL-2 were observed. Moreover, treatment by this construct decreased the production of ROS, LPO, BUN, and Cr and improved tissue damage. Conclusion: The use of a microneedle patch containing exosomes is a noninvasive method that enables the release of exosomes in a slow manner. In comparison to exosome injection alone, microneedle patch-exosome treatment offers a longer and more targeted effect that improves renal IRI dysfunction and reduces tissue damage, potentially facilitating the clinical application of exosomes and improving graft survival.

Pulmonary fibrosis (PF) is a lethal pathological change of fibrotic interstitial lung diseases (ILDs) with abundant fibroblasts proliferation after severely or continually alveolar epithelial cells (AECs) injury. Barely therapies are helpful for PF. Here we use bleomycin intratracheally injection to model PF with or without human umbilical cord-mesenchymal stem cells (hUC-MSCs) and/or nintedanib intervention. RNA-Seq followed with real-time PCR and western blot were used to find out the specific possible mechanisms of the effects of hUC-MSC and nintedanib on PF. Immunostaining, cell counting kit-8 (CCK-8), and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay were used to detect the cell proliferation in vivo or in vitro separately. We found that hUC-MSCs alone had prophylactic, but not therapeutic effects on bleomycin induced mouse PF. Nevertheless, the combination therapy of hUC-MSCs and low-dose nintedanib significantly improved survival and reversed lung fibrosis in PF model mice. The factors secreted by hUC-MSCs have promotional effects on the proliferation both of fibroblasts and AECs. Nintedanib could hamper the facilitation of fibroblasts caused by hUC-MSCs without influence on AECs proliferation, which might be related with the inhibition on FGFR, PDGFR, and VEGFR activities. Our study indicated that the combination therapy of hUC-MSCs and nintedanib should be a promising strategy for PF.