Stem Cells International最新文献

Liver hepatocellular carcinoma (LIHC) is a prevalent and highly aggressive form of liver cancer, characterized by increasing rates of incidence and mortality globally. Although numerous treatment options currently exist, they frequently result in insufficient clinical outcomes for those diagnosed with LIHC. This highlights the urgent need to identify new biomarkers that can enhance prognostic evaluations and support the development of more effective therapeutic strategies for LIHC. Through the use of the SwissTargetPrediction tool, we precisely identified molecular targets related to Sorafenib. Furthermore, analysis of RNA sequencing data from the TCGA-LIHC cohort uncovered 24 genes associated with different patient prognoses following Sorafenib therapy. Employing a clustering-based analytical approach, we assessed the connections between gene expression profiles, clinical outcomes, immune cell infiltration levels, and tumor stage progression. A prognostic framework was constructed by applying various machine learning techniques and subsequently validated across several independent datasets. Utilizing the XgBoost algorithm, MAPK12 emerged as a key regulatory gene influencing the prognosis of individuals with LIHC. The results of in vitro experiments demonstrated that knockdown of MAPK12 reduced the proliferation, metastasis, and tumor stemness-related sphere-forming ability of LIHC cells. These results underscore the promise of MAPK12 as a potential prognostic biomarker for LIHC and offer valuable insights for crafting personalized treatment approaches.

Tumor surgery or trauma in the maxillofacial region may cause injuries to peripheral nerves, such as facial nerves. The gold standard of treatment for peripheral nerve injury has been autologous nerve grafting. Since new peripheral nerve regeneration technologies are required, three-dimensional (3D) structures fabricated only from cells by using Bio 3D printers are attracting attention. Dental pulp stem cells (DPSCs) are a promising option as a cell source because of their high clonogenic, proliferative, and multidifferentiation potentials. In this study, nerve conduits were fabricated from DPSCs using a Bio 3D printer, and their potential for nerve regeneration was evaluated in a rat facial nerve injury model. DPSCs were obtained from wisdomteeth of patients and cultured. A 5 mm Bio 3D conduit was fabricated by using a Bio 3D printer. Six F344 rnu-/rnu- rats with immune deficiency (10 weeks old, body weight: 190-240 g) were divided into two groups: a Bio 3D group (n = 3) and a silicone tube group (n = 3). The 5 mm Bio 3D conduits and silicone tubes were transplanted into 4 mm defects. Evaluation was performed at 12 weeks after the surgery. The whiskers of immunodeficient rats in both groups were moving. The number of myelinated axons was larger in the Bio 3D group than in the silicone group. Myelinated axon diameter (MAD) and myelin thickness (MT) of regenerated axons in the Bio 3D group were significantly greater than those in the silicone group (MAD: p  < 0.01, MT: p  < 0.05). In this study, we confirmed the nerve regeneration potential of Bio 3D structures fabricated from DPSCs that were transplanted into a rat model of facial nerve injury.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease and is a comorbidity in type 2 diabetes (T2D) mellitus. Mesenchymal stem cell (MSC) is emerging as a potential therapeutic strategy for diabetes and NAFLD through mitochondrial transfer initiated by signaling from injured recipient cells. Thus, in this study, we investigated whether exogenous mitochondrial preconditioning of MSCs could exert superior effects on NAFLD and explore the role of MSCs-mediated mitochondrial transfer into hepatocyte. Methods: After free HepG2 mitochondria pretreated, umbilical cord-derived MSCs (UC-MSCs) (mito-MSCs), T2D model mice were infused with equal amounts of MSCs/mito-MSCs via the tail vein once a week for 4 weeks. Body weight and random blood glucose were monitored weekly. After the end of treatment, the mitochondrial transfer level of MSCs before and after pretreatment were monitored by fluorescence tracing. Blood and liver were collected for biochemical and histopathological examinations. The number, morphology, and function of mitochondria in liver tissue were evaluated by tissue electron microscopy and western blot analysis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to monitor the expression of genes associated with lipid metabolism and regulation pathways. Results: Pretreatment of UC-MSCs enhanced the efficacy of MSCs in lowering blood glucose, liver transaminase, triglyceride levels, and reducing histological damage, which may be related to free mitochondria triggering autophagy of MSCs, which in turn promoted the entry of MSCs mitochondria into the liver tissue of diabetic mice. Conclusion: Exogenous mitochondria could enhance the therapeutic efficacy of MSCs in NAFLD via mediating mitochondrial transfer, which offers a novel strategy for the improving the outcomes of MSCs cell-therapy for diabetes-related NAFLD.

Acute and chronic neurodegenerative conditions (NDs) are major causes of disability and mortality worldwide. Acute NDs encompass conditions such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). On the other hand, chronic NDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Currently, no definitive cure exists for these diseases, and available therapies focus primarily on slowing the progression of symptoms. Mesenchymal stem cells (MSCs), due to their multilineage differentiation capacity, immunomodulatory abilities, and regenerative properties, have gained attention in regenerative medicine. In recent years, extracellular vesicles (EVs) derived from MSCs have shown great promise as a cell-free therapeutic approach, eliminating the risks associated with direct MSCs use, such as tumorigenicity and poor cell survival after transplantation. EVs have emerged as powerful mediators of intercellular communication and tissue repair, exhibiting immunomodulatory, anti-inflammatory, and proregenerative properties. However, limitations such as low EVs yield and reduced efficacy due to MSCs replicative senescence restrict their therapeutic potential. Preconditioning strategies, including hypoxia, 3D cultures, and biochemical priming, have been explored in other fields to enhance EVs properties, yet their specific application to NDs remains under-reported. This review aims to address this gap by analyzing the preconditioning methods used to boost the therapeutic potential of MSCs-derived EVs for neurodegenerative diseases. These preconditioning strategies may enhance EVs yield, functional cargo, and targeted therapeutic efficacy for treating acute and chronic NDs.

Aims: Inflammation is a key process involved in the early stages of periodontal regeneration, where immune cells are responsible for the recruitment of osteoblast to facilitate periodontal regeneration. The aim of the present study was to explore the effect of platelet-rich fibrin (PRF) on macrophage polarization, and thereafter to investigate its effect on osteoblast recruitment to enhance early-stage periodontal regeneration. Materials and Methods: The extracted liquids of PRF, produced using fixed-angled and horizontal centrifugation protocols, were utilized to stimulate Thp1 to study macrophage proliferation and polarization. Thereafter, the supernatants of Thp1 were collected and utilized to stimulate the migration of human bone marrow osteoblasts, to investigate the recruitment of osteoblast via macrophage polarization. Results: PRF stimulated the proliferation and recruitment of macrophages, with horizontal centrifugation protocols demonstrating significantly greater potential when compared to fixed-angled. Furthermore, PRF was able to enhance the recruitment of osteoblast via macrophage polarization, with horizontal platelet-rich fibrin (H-PRF) demonstrating the most significant increase. Conclusion: The present study explored a promising mechanism of the periodontal regeneration function of PRF, by inducing macrophage polarization, thereby enhancing osteoblast recruitment, with horizontal centrifugation significantly improving these findings.

Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs. Kruppel-like factor 5 (KLF5) is a significant transcription factor involved in maintaining stem cell properties. In this study, we aimed to investigate whether overexpression of KLF5 could enhance the cardioprotective characteristics of BMSCs, particularly in terms of mitigating structural and electrical remodeling. Our in vivo experiments revealed that transplantation of KLF5-overexpressing BMSCs in mice with MI led to a substantial reduction in ventricular fibrosis and the occurrence of ventricular arrhythmias (VAs). In vitro coculture experiments demonstrated that BMSCs could inhibit CFs activation and cytoskeleton protein bundling induced by hypoxia through paracrine effects, resulting in reduced expression of α-SMA and Collagen I. Furthermore, coculturing BMSCs significantly reduced the expression of connexin 43, alleviated hypoxia, increased the expression of inward-rectifier K⁺ current (Kir), and decreased voltage-dependent K⁺ (Kv) currents. Mechanistically, KLF5 enhanced the effects of BMSCs by facilitating the transfer of miR-152-3 p from BMSCs-derived exosomes to CFs. Overall, our findings show that BMSCs transplantation promotes the recovery of cardiac function and reduces the incidence of arrhythmias by inhibiting CFs activation and modulating CFs Kir current remodeling. Additionally, overexpression of KLF5 enhances the cardioprotective effects of BMSCs.

Lacrimal gland (LG) dysfunction diseases are a type of disorder caused by various etiologies that damage the LG tissue, reducing lacrimal fluid secretion, triggering aqueous-deficient dry eye (ADDE), and causing a series of complications like keratoconjunctivitis sicca, potentially threatening vision. Our review summarizes the limitations and new progress of traditional treatment methods for LG dysfunction diseases. Meanwhile, we conduct in-depth analyses closely centered on the two emerging and cutting-edge research hotspots, namely stem cell therapy and organoid therapy. We have comprehensively evaluated the current research status regarding various stem cells, their derived extracellular vesicles, and LG organoid transplantation, further discussed the existing deficiencies, and subsequently put forward the prospective directions for future research. These include developing ophthalmic preparations of extracellular vesicles and LG stem cells or searching more efficient drug delivery systems, as well as culturing LG organoids that are highly similar to human lacrimal glands (LGs) in both function and microstructure through magnetic three-dimensional (3D) bioprinting technology and microfluidic 3D bioprinting technology.

Exosomes are naturally occurring cellular products released by various cell types in the body. Their composition is similar to that of human tissues, which reduces the risk of immune rejection. As critical mediators of intercellular communication, exosomes transmit signals and information that regulate the physiological states of surrounding tissues. Depending on their cellular origin and molecular content, exosomes can either promote nerve regeneration and functional recovery at the site of spinal cord injury (SCI) or exacerbate the local injury microenvironment. However, as a cellular product, the composition and function of exosomes are affected by the type and state of the cells from which they originate, and thus, there may be specificity problems in treatment, such as the possible instability of the therapeutic effect, et cetera. Moreover, exosomes need to be further optimized in terms of their delivery and release strategies in order to improve the duration and stability of the therapeutic effect. Thus, a single therapy approach is often insufficient to effectively support nerve repair following SCI. Numerous studies have demonstrated that encapsulating exosomes within biomaterial scaffolds enhances their delivery and retention at the injury site, thereby improving their viability. This paper reviews the latest research on stem cell-derived exosomes and biomaterials in the context of SCI. It further explores the combined application of exosomes and biomaterial scaffolds in SCI treatment, while also addressing the associated challenges and future prospects.

Lyme disease (LD), a zoonotic infectious disease caused by Borrelia burgdorferi (B. burgdorferi), can affect various organs, including the skin, heart, nervous system, and joints. Lyme arthritis (LA) is the most common and severe late-stage presentation of LD, often presenting with intermittent joint swelling and pain. Although antibiotics are effective in most patients with LA, some patients may continue to experience arthritis symptoms for months or years after standard treatment, which poses a serious threat to their quality of life. Therefore, more effective treatments are urgently needed. The purpose of this study was to evaluate the therapeutic effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on LD in Kunming (KM) mice. A bilateral hind limb LA model was established by infecting KM mice with B. burgdorferi. Low and high doses of hUC-MSCs (1 × 10⁶ and 2 × 10⁶ cells, respectively) were injected (one time every 2 days) into the right tibiotalar joints of the mice, whereas the left tibiotalar joints were pricked without injecting cells (sham operation). The therapeutic effects of the hUC-MSCs were evaluated through morphological examination, measurement of hind limb diameter, imaging assessment (X-ray), and measurement of inflammatory factor levels. Spirochete burden was assessed by quantitative real-time polymerase chain reaction (qPCR). Morphological, hind limb diameter, and imaging analyses showed that the low and high hUC-MSC doses significantly reduced bilateral hind limb swelling in the LA mice. Histological (hematoxylin and eosin staining) examination of tibiotalar joint sections showed that when compared with the control group, inflammatory cell infiltration, and bilateral hind limb tissue damage were reduced in the two treatment groups. Enzyme-linked immunosorbent assays revealed that the levels of IL-6 and TNF-α in lysates from the bilateral tibiotarsal joints were significantly lower in the two treatment groups than in the control group. QPCR results showed that hUC-MSCs treatment had no significant effect on the spirochete load in the tibiotarsal joint. Our findings indicate that hUC-MSCs can alleviate inflammation in the KM mouse model of LA without increasing B. burgdorferi burden., which is expected to be a new potential method for the treatment of LA.

Circadian rhythm abnormalities due to sleep deprivation (SD) may promote the development of emotional and cognitive disorders. Though light therapies have been employed to treat circadian disorders, the exact treatments and their underlying biology are still unclear. Our study aimed to investigate the effects of intrinsically photosensitive retinal ganglion cells (ipRGCs) sensitive 480 nm blue light on circadian rhythms affecting emotional and cognitive behaviors and the expression of neural stem cells (NSCs) stemness genes. In this study, we demonstrate that for mice with acute SD for 24 h, exposure to ipRGCs sensitive 480 nm blue light at ~ 1300 lux for 30 min at 8:00 a.m. and 8:00 p.m. improves the stability of disrupted clock genes, increases nocturnal activity, reduces anxiety-like behaviors, and enhances cognitive abilities. Furthermore, 480 nm blue light exposure reduces fluctuations in NSCs stemness gene expression induced by SD, potentially through its effect on enhancing the amplitude of suprachiasmatic nucleus (SCN) circadian oscillations. These findings may provide novel strategy for alleviating rotating circadian rhythm-related anxiety and learning and cognitive obstruction.