Stem Cells International最新文献

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.

A proper source of stem cells is key to muscle injury repair. Dental pulp stem cells (DPSCs) are an ideal source for the treatment of muscle injuries due to their high proliferative and differentiation capacities. However, the current myogenic induction efficiency of human DPSCs hinders their use in muscle regeneration due to the unknown induction mechanism. In this study, we treated human DPSCs with Noggin, a secreted antagonist of bone morphogenetic protein (BMP), and discovered that Noggin can effectively promote myotube formation. We also found that Noggin can accelerate the skeletal myogenic differentiation (MyoD) of DPSCs and promote the generation of Pax7⁺ satellite-like cells. Noggin increased the expression of myogenic markers and the transcriptional and translational abundance of satellite cell (SC) markers in DPSCs. Moreover, BMP4 inhibited Pax7 expression and activated p-Smad1/5/9, while Noggin eliminated BMP4-induced p-Smad1/5/9 in DPSCs. This finding suggests that Noggin antagonizes BMP by downregulating p-Smad and facilitates the MyoD of DPSCs. Then, we implanted Noggin-pretreated DPSCs combined with Matrigel into the mouse tibialis anterior muscle with volumetric muscle loss (VML) and observed a 73% reduction in the size of the defect and a 69% decrease in scar tissue. Noggin-treated DPSCs can benefit the Pax7⁺ SC pool and promote muscle regeneration. This work reveals that Noggin can enhance the production of satellite-like cells from the MyoD of DPSCs by regulating BMP/Smad signaling, and these satellite-like cell bioconstructs might possess a relatively fast capacity for muscle regeneration.

Transient receptor potential ankyrin 1 (TRPA1) molecule is an important type of transient receptor potential (TRP) cation channels, which can cause extracellular Ca²⁺ to flow into cells after activation. TRPA1 plays an important role in acute and chronic pain, inflammation, kidney disease, cough and asthma, osteoarthritis, cardiovascular disease, obesity, diabetes, and other diseases. In this study, the expression of interleukin (IL)-1β, IL-6, and IL-8 in periodontal ligament stem cells (PDLSCs) treated by lipopolysaccharide (LPS) and the effect of LPS on PDLSCS proliferation were detected. Meanwhile, the change in TRPA1 expression in PDLSCs treated by LPS was also assessed. By knocking down the expression of TRPA1 and using the TRPA1 antagonist HC-030031, the expression of IL-1β, IL-6, and IL-8 in PDLSCs treated by LPS was downregulated. After LPS stimulation, the proliferation ability of PDLSCs decreased, the gene expression and secretion of IL-1β, IL-6, and IL-8 increased and the gene and protein expression of TRPA1 were upregulated. Reducing the expression of TRPA1 can effectively inhibit the increase of gene expression of IL-1β, IL-6, and IL-8 after LPS stimulation, and pretreatment of PDLSCs with HC-030031 can also achieve the above effect. And research has found that HC-030031 can inhibit the phosphorylation level of JNK in PDLSCs treated by LPS. The use of JNK inhibitor JNK-IN-8 can also reduce the expression of IL-1β, IL-6, and IL-8 in PDLSCs. Finally, this study found LPS could cause the upregulation of TRPA1, and the inhibition of TRPA1 could produce an anti-inflammatory effect in PDLSCs treated by LPS due to its inhibition of JNK phosphorylation.

Background: Burns are a global public health issue and a major cause of disability and death around the world. Stem cells, which are the undifferentiated cells with the potential for indefinite proliferation and multilineage differentiation, have the ability to replace injured skin and facilitate the wound repair process through paracrine mechanisms. In light of this, the present study aims to conduct a bibliometric analysis in order to identify research hotspots of stem cell-related burns and assess global research tendencies. Methods: To achieve this objective, we retrieved scientific publications on burns associated with stem cells covering the period from January 1, 1978, to October 13, 2022, from the Web of Science Core Collection (WoSCC). Bibliometric analyses, including production and collaboration analyses between countries, institutions, authors, and journals, as well as keyword and topic analyses, were conducted using the bibliometrix R package, CiteSpace, and VOSviewer. Results: A total of 1648 burns associated with stem cell documents were published and listed on WOSCC. The most contributive country, institution, journal, and author were the United States, LV Prasad Eye Institute, Burns, and Scheffer C.G. Tseng, respectively. More importantly, combined with historical direct citation network, trend topic analysis, keyword co-occurrence network, and substantial literature analysis, we eventually summarized the research hotspots and frontiers on burns associated stem cell reasearch. Conclusion: The present study obtained deep insight into the developing trends and research hotspots on burns associated with stem cells, which arouses growing concerns and implies increasing clinical implications. The mechanism and therapeutics of epidermal stem cells (ESCs) for burn wounds and the mechanism of mesenchymal stem cells (MSCs) and MSC-derived exosomes for burns wounds are two research hotspots in this field.

Renal diseases, particularly acute kidney injury (AKI) and chronic kidney disease (CKD), are significant global health challenges. These conditions impair kidney function and can lead to serious complications, including cardiovascular diseases, which further exacerbate the public health burden. Currently, the global AKI mortality rate is alarmingly high (20%-50%); CKD is projected to emerge as a major global health burden by 2040. Existing treatments such as hemodialysis and kidney transplantation have limited effectiveness and are often associated with adverse effects. Mesenchymal stem cells (MSCs) offer considerable potential for treating renal diseases owing to their regenerative and immunomodulatory properties. Thus, this review focuses on the application of MSCs in renal disease, discusses fundamental research findings, and evaluates their application in clinical trials. Moreover, we discuss the impact and safety of MSCs as a therapeutic option and highlight challenges and potential directions for their clinical application. We selected research articles from PubMed published within the last 5 years (from 2019), focusing on high-impact journals and clinical trial data, and included a few key studies predating 2019. Considerations included the novelty of the research, sample size, experimental design, and data reliability. With advancements in single-cell sequencing, CRISPR/Cas9 gene editing, and other cutting-edge technologies, future MSC research will explore combination therapies and personalized treatments to provide more promising, safer treatments with reduced adverse reactions and enhanced therapeutic outcomes. These advances will improve kidney disease treatment methods, enhance patient quality of life, and maximize the benefits of MSC therapies.

Human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have emerged as a promising source of autologous cells with great potential to produce novel cell therapy for ischemic vascular diseases. However, their clinical application still faces numerous challenges including safety concerns such as the potential aberrant immunogenicity derived from the reprogramming process. This study investigated immunological phenotypes of iPSC-ECs by a side-by-side comparison with primary human umbilical vein ECs (HUVECs). Three types of human iPSC-ECs, NIBSC8-EC generated in house and two commercial iPSC-ECs, alongside HUVECs, were examined for surface expression of proteins of immune relevance under resting conditions and after cytokine activation. All iPSC-EC populations failed to express major histocompatibility complex (MHC) Class II on their surface following interferon-gamma (IFN-γ) treatment but showed similar basal and IFN-γ-stimulated expression levels of MHC Class I of HUVECs. Multiple iPSC-ECs also retained constitutive and tumor necrosis factor-alpha (TNF-α)-stimulated expression levels of intercellular adhesion molecule-1 (ICAM-1) like HUVECs. However, TNF-α induced a differential expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) on iPSC-ECs. Furthermore, real-time monitoring of proliferation of human peripheral blood mononuclear cells (PBMCs) cocultured on an endothelial monolayer over 5 days showed that iPSC-ECs provoked distinct dynamics of PBMC proliferation, which was generally decreased in alloreactivity and IFN-γ-stimulated proliferation of PBMCs compared with HUVECs. Consistently, in the conventional mixed lymphocyte reaction (MLR), the proliferation of total CD3+ and CD4+ T cells after 5-day cocultures with multiple iPSC-EC populations was largely reduced compared to HUVECs. Last, multiple iPSC-EC cocultures secreted lower levels of proinflammatory cytokines than HUVEC cocultures. Collectively, iPSC-ECs manifested many similarities, but also some disparities with a generally weaker inflammatory immune response than primary ECs, indicating that iPSC-ECs may possibly exhibit hypoimmunogenicity corresponding with less risk of immune rejection in a transplant setting, which is important for safe and effective cell therapies.