Metformin Ameliorates D-Galactose-Induced Senescent Human Bone Marrow-Derived Mesenchymal Stem Cells by Enhancing AutophagyRead the full article
Stem Cells International publishes papers in all areas of stem cell biology and applications. The journal publishes basic, translational, and clinical research, including animal models and clinical trials.
Chief Editor Professor Li has a background in cardiac stem cell transplantation, using young stem cells to promote tissue repair following injury to rejuvenate the aged individual, and the development of biomaterials that can easily integrate into damaged heart tissue.
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Application of Dental Pulp Stem Cells for Bone and Neural Tissue Regeneration in Oral and Maxillofacial Region
In the oral and maxillofacial region, the treatment of severe bone defects, caused by fractures, cancers, congenital abnormalities, etc., remains a great challenge. In addition, neurological disorders are frequently accompanied by these bone defects or the treatments for them. Therefore, novel bone regenerative techniques and methods to repair nerve injury are eagerly sought. Among them, strategies using dental pulp stem cells (DPSCs) are promising options. Human DPSCs can be collected easily from extracted teeth and are now considered a type of mesenchymal stem cell with higher clonogenic and proliferative potential. DPSCs have been getting attention as a cell source for bone and nerve regeneration. In this article, we reviewed the latest studies on osteogenic or neural differentiation of DPSCs as well as bone or neural regeneration methods using DPSCs and discussed the potential of DPSCs for bone and nerve tissue regeneration.
hUMSCs Restore Uterine Function by Inhibiting Endometrial Fibrosis via Regulation of the MMP-9/TIMP-1 Ratio in CDDP-Induced Injury Rats
The fertility of females of childbearing age who are cured of cancer by chemotherapy is gradually declining globally. As a broad-spectrum chemotherapy drug in clinic, the damage of cisplatin (CDDP) to female reproductive function cannot be ignored. At present, the study of CDDP damage to the uterus is not sufficient, and the exact mechanism needs to be further explored. Therefore, we conducted this research to determine whether uterine injury in CDDP-induced injury rats might be improved by human umbilical cord mesenchymal stem cells (hUMSCs) and to further explore the precise mechanism. The rat model of CDDP-induced injury was established by intraperitoneal injection of CDDP, and hUMSCs were injected into the tail vein 7 days later. In vivo, uterine function in CDDP-induced injury rats was affected after hUMSC transplantation. In vitro, the specific mechanism was further explored from the cell and protein levels. Overall, the specific reason of CDDP-induced uterine dysfunction in rats was endometrial fibrosis, which was significantly improved after hUMSC transplantation. Further investigation of the mechanism found that hUMSCs could regulate the ratio of matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in endometrial stromal cells (EnSCs) after CDDP injury.
Intravenously Administered Human Umbilical Cord-Derived Mesenchymal Stem Cell (HucMSC) Improves Cardiac Performance following Infarction via Immune Modulation
Overactive inflammatory responses contribute to progressive cardiac dysfunction after myocardial infarction (MI). Mesenchymal stem cell (MSC) has generated significant interest as potent immune modulators that can regulate excessive immune responses. We hypothesized that intravenous (iv) administration of human umbilical cord-derived MSC (HucMSC) exerts systemic and local anti-inflammation effects, leading to improved heart function after MI. In murine MI models, we confirmed that single iv administration of HucMSC () improved cardiac performance and prevented adverse remodeling after MI. A small proportion of HucMSC is trafficked to the heart, preferentially in the infarcted region. HucMSC administration increased CD3+ T cell proportion in the periphery while decreased T cell proportion in both infarcted heart and mediastinal lymph nodes (med-LN) at 7-day post-MI, indicating a systematic and local T cell interchange mediated by HucMSC. The inhibitory effects of HucMSC on T cell infiltration in the infarcted heart and med-LN sustained to 21-day post-MI. Our findings suggested that iv administration of HucMSC fostered systemic and local immunomodulatory effects that contributed to the improvement of cardiac performance after MI.
Extracellular Vesicles Secreted by TGF-β1-Treated Mesenchymal Stem Cells Promote Fracture Healing by SCD1-Regulated Transference of LRP5
Bone fracture repair is a multiphased regenerative process requiring paracrine intervention throughout the healing process. Mesenchymal stem cells (MSCs) play a crucial role in cell-to-cell communication and the regeneration of tissue, but their transplantation is difficult to regulate. The paracrine processes that occur in MSC-derived extracellular vesicles (MSC-EVs) have been exploited for this study. The primary goal was to determine whether EVs secreted by TGF-β1-stimulated MSCs (MSCTGF-β1-EVs) exhibit greater effects on bone fracture healing than EVs secreted by PBS-treated MSCs (MSCPBS-EVs). Our research was conducted using an in vivo bone fracture model and in vitro experiments, which included assays to measure cell proliferation, migration, and angiogenesis, as well as in vivo and in vitro gain/loss of function studies. In this study, we were able to confirm that SCD1 expression and MSC-EVs can be induced by TGF-β1. After MSCTGF-β1-EVs are transplanted in mice, bone fracture repair is accelerated. MSCTGF-β1-EV administration stimulates human umbilical vein endothelial cell (HUVEC) angiogenesis, proliferation, and migration in vitro. Furthermore, we were able to demonstrate that SCD1 plays a functional role in the process of MSCTGF-β1-EV-mediated bone fracture healing and HUVEC angiogenesis, proliferation, and migration. Additionally, using a luciferase reporter assay and chromatin immunoprecipitation studies, we discovered that SREBP-1 targets the promoter of the SCD1 gene specifically. We also discovered that the EV-SCD1 protein could stimulate proliferation, angiogenesis, and migration in HUVECs through interactions with LRP5. Our findings provide evidence of a mechanism whereby MSCTGF-β1-EVs enhance bone fracture repair by regulating the expression of SCD1. The use of TGF-β1 preconditioning has the potential to maximize the therapeutic effects of MSC-EVs in the treatment of bone fractures.
Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair
Tendons are associated with a high injury risk because of their overuse and age-related tissue degeneration. Thus, tendon injuries pose great clinical and economic challenges to the society. Unfortunately, the natural healing capacity of tendons is far from perfect, and they respond poorly to conventional treatments when injured. Consequently, tendons require a long period of healing and recovery, and the initial strength and function of a repaired tendon cannot be completely restored as it is prone to a high rate of rerupture. Nowadays, the application of various stem cell sources, including mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs), for tendon repair has shown great potential, because these cells can differentiate into a tendon lineage and promote functional tendon repair. However, the mechanism underlying tenogenic differentiation remains unclear. Moreover, no widely adopted protocol has been established for effective and reproducible tenogenic differentiation because of the lack of definitive biomarkers for identifying the tendon differentiation cascades. This work is aimed at reviewing the literature over the past decade and providing an overview of background information on the clinical relevance of tendons and the urgent need to improve tendon repair; the advantages and disadvantages of different stem cell types used for boosting tendon repair; and the unique advantages of reported strategies for tenogenic differentiation, including growth factors, gene modification, biomaterials, and mechanical stimulation.
Regenerative Potential of Granulation Tissue in Periodontitis: A Systematic Review and Meta-analysis
Background and Aim. Soft and hard periodontal tissues contain limited numbers of stem cells. This makes regeneration of the periodontium in patients with periodontitis challenging and unpredictable. Granulation tissue is traditionally removed during periodontal corrective therapy, but it is believed to contain multipotent stem cells which could be used for regenerative therapy. The aim of this research was to critically appraise the evidence on cellular components within granulation tissue in patients with periodontitis and its regenerative potential when compared to control healthy periodontal tissue. Methods. Electronic searches were conducted in five databases including CENTRAL, MEDLINE, EMBASE, Web of Science, and Dentistry & Oral Sciences Source using a combination of MeSH terms and keywords up to 21 June 2022. Human studies including patients aged over 18 years with all forms of periodontitis were included. Following the risk of bias assessment, both qualitative and quantitative analyses were performed. Results. A total of twelve studies were included in qualitative analysis and six of them in quantitative analyses. The evidence suggested that cells derived from periodontitis granulation tissue have osteogenic, adipogenic, chondrogenic, neurogenic, and angiogenic differentiation abilities as well as immunoregulatory properties. In particular, CD44+, CD73+, CD90+, CD105+, and CD146+ cells were found widely in granulation tissue whilst the only meta-analysis confirmed that CD90+ cells were present in lower numbers within the granulation tissue when compared with healthy periodontal tissue (, 95% CI -30.43 to -16.44, ). Conclusions. This review provided further evidence that granulation tissue from patients with periodontitis can be a potential stem cell source for regenerative therapy.