Current stem cell research & therapy最新文献

Bone and cartilage regeneration is a dynamic and complex process involving multiple cell types, such as osteoblasts, osteoclasts, endothelial cells, etc. Stem cells have been proved to have an efficient capability to promote bone and cartilage regeneration and repair, but the usage of cells harbors some important safety issues, such as immune rejection and carcinogenicity. Exosomes are non-cell structures secreted from various cells. The content of exosomes is enriched with proteins, such as cytoskeleton proteins, adhesion factors, transcription factors, etc., and a variety of nucleic acids, such as mRNA (Messenger RNA), long-chain non-coding RNA, microRNA (miRNA), etc. Exosomes can deliver a variety of contents from the parent cells to the recipient cells in different tissue backgrounds, influencing the phenotype and function of the recipient cells. Recent studies have demonstrated that miRNAs play significant roles in bone formation, suggesting that miRNAs may be novel therapeutic targets for bone and cartilage diseases. Exosomes have been shown with low/no immune rejection in vivo, no carcinogenic risk of infection, nor other side effects. In recent years, stem cell exosomes have been utilized to promote bone and cartilage regeneration processes during bone defect, bone fracture, cartilage repair, osteoporosis, and osteoarthritis. In this review, we discuss different exosomes derived from stem cells and their interactions with target cells, including osteoblasts, chondrocytes and osteoclasts. We also highlight the various signaling pathways involved in stem cell exosome-related bone and cartilage regeneration.

Moyamoya disease (MMD) is a chronic steno-occlusion cerebrovascular disease accompanied by the formation of the abnormal vascular network at the base of the brain. The etiology of MMD is not fully clarified. Lack of pathological specimens hinders the research progress. Induced pluripotent stem cells (iPSC) derived from patients with outstanding differentiation potential and infinite proliferation ability could conquer the problem of insufficient samples. The technology of iPSC holds the promise of clarifying the underlying molecular mechanism in the development of MMD. In this review, we summarized the latest progress and difficulties in the research of mechanism and detailed the application of iPSC in MMD, aiming to provide an outlook of iPSC in molecular mechanism and novel therapies of MMD.

Background: Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in polyvinyl chloride products which is widely utilized. Previously we found, DEHP reduced the viability and proliferation ability of bone marrow mesenchymal stem cells (BMSCs).

Objective: In the present study, the mechanism of DEHP toxicity was investigated.

Methods: Rat BMSCs were cultured up to 3^rd passage and their viability was determined after treatment with 100 and 500 μM of DEHP for 24 and 48 hours. The levels of sodium, potassium, and calcium as well as induction of apoptosis were investigated. Using flow cytometry, cell cycle analysis was performed and the expression of genes involved in the cell cycle was evaluated using reverse transcriptase-PCR. Data were analyzed and p < 0.05 was taken as the level of significance.

Results: Although the viability and electrolyte level of BMSCs were not affected with 100 μM of DEHP, this environmental pollution induced caspase-dependent apoptosis in a concentration-dependent manner. In both of the concentrations, DEHP arrests the cell cycle at the G0/G1 phase, and the expression of Cdk2 and Cdk4 was significantly reduced whereas an over-expression of P53 was observed. However, the expression of the raf1 gene remained unchanged.

Conclusion: DEHP induces caspase-dependent apoptosis in BMSCs and arrests the cell cycle due to the reduction of Cdk2 and Cdk4 expression via over-expression of P53.

In the last two decades, fetal amniotic fluid stem cells progressively attracted attention in the context of both basic research and the development of innovative therapeutic concepts. They exhibit broadly multipotent plasticity with the ability to differentiate into cells of all three embryonic germ layers and low immunogenicity. They are convenient to maintain, highly proliferative, genomically stable, non-tumorigenic, perfectly amenable to genetic modifications, and do not raise ethical concerns. However, it is important to note that among the various fetal amniotic fluid cells, only c-Kit+ amniotic fluid stem cells represent a distinct entity showing the full spectrum of these features. Since amniotic fluid additionally contains numerous terminally differentiated cells and progenitor cells with more limited differentiation potentials, it is of highest relevance to always precisely describe the isolation procedure and characteristics of the used amniotic fluid-derived cell type. It is of obvious interest for scientists, clinicians, and patients alike to be able to rely on up-todate and concisely separated pictures of the utilities as well as the limitations of terminally differentiated amniotic fluid cells, amniotic fluid-derived progenitor cells, and c-Kit+ amniotic fluid stem cells, to drive these distinct cellular models towards as many individual clinical applications as possible.

Osteoporosis is a systemic disease in which bone mass decreases, leading to an increased risk of bone fragility and fracture. The occurrence of osteoporosis is believed to be related to the disruption of the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. N6-adenylate methylation (m6A) modification is the most common type of chemical RNA modification and refers to a methylation modification formed by the nitrogen atom at position 6 of adenine (A), which is catalyzed by a methyltransferase. The main roles of m6A are the post-transcriptional level regulation of the stability, localization, transportation, splicing, and translation of RNA; these are key elements of various biological activities, including osteoporosis and the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. The main focus of this review is the role of m6A in these two biological processes.

Aim: The study aims to investigate the immunomodulatory effect of Amniotic fluid stem (AFS) cells to Th2-skewed allergic rhinitis (AR) on T-lymphocyte proliferation, viability, activation and cytokine production.

Background: AFS cells can suppress peripheral blood mononuclear cells (PBMCs) proliferation and display immunomodulatory properties, but AFS cells' immunoregulation on AR has not been defined.

Methods: Human AFS cells were derived from magnetic cell sorting and co-cultured with PBMCs from AR patients stimulated by phytohemagglutinin (PHA). The AFS cells-associated suppressive proliferation was analyzed using CellTrace™ Violet assay; the T lymphocytes proliferation, viability, activation and the Foxp3⁺ Treg cells were determined by flow cytometry; cytokine levels were measured using an enzyme- linked immunosorbent assay.

Results: We determined that AFS cells significantly inhibited PHA-induced CD3⁺ T lymphocyte proliferation at the ratio higher than 1:50 (AFS cells: PBMCs) (P<0.05); AFS cells obviously increased the T lymphocytes viability (P<0.01), inhibited the apoptosis of T lymphocytes (P<0.001), compared to PBMCs alone; AFS cells suppressed CD3⁺CD25⁺ T lymphocytes activated by PHA (P<0.05); AFS cells significantly promote Treg cells expansion in house dust mite (HDM)-stimulated PBMCs from AR patients (P<0.05). Compared with HDM-stimulated PBMCs, AFS cell co-culture predominantly decreased IL-4 level (P<0.05), but increased IFN-γ and IL-10 levels (P<0.01).

Conclusion: AFS cells modulate the T-cells' immune imbalance towards Th2 suppression in AR, which can be used as a new cell banking for allergic airway diseases.

Cancer stem cells (CSCs) are correlated with poor clinical outcomes due to their contribution to chemotherapy resistance and the formation of metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs, which is important for diagnosis, therapy, and prognosis. This review underlines the role of CSCs and circulating tumor cells (CTCs) in tumor relapse and metastasis, the characteristics of CSC and CTC biomarkers, and the techniques used to detect these cells. We also summarized novel therapeutic approaches toward targeting CSCs, especially focusing on the role of immune checkpoint blockades (ICB), such as anti-programmed death 1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PDL1) therapies. Additionally, we address an intriguing new mechanism of action for small molecular drugs, such as telomere-targeted therapy 6-thio-2'deoxyguanosine (6- thio-dG), and how it reshapes tumor microenvironment to overcome ICB resistance. There are indications, that personalized cancer therapy targeting CSC populations in conjunction with immune-mediated strategy hold promise for the removal of residual therapy-resistant CSCs in the near future.

Background: Endometrial injury is considered the major cause of female infertility. Traditional therapies such as estrogen substitution therapy are not satisfactory due to individual variation in response to treatment, thereby warranting the use of alternative strategies such as stem cell therapy. Transplantation of stem cells, such as umbilical cord mesenchymal stem cells (UCMSCs), has been shown to improve endometrial healing. However, due to the effect of the intrauterine environment, the therapeutic effect of UCMSCs is limited, and its efficacy is unstable. HOXA10, encoded by the HOXA10 gene, plays an important role in endometrium morphology maintenance, proliferation, differentiation, and embryo implantation. Moreover, UCMSCs do not show HOXA10 expression.

Objective: Our study aimed to evaluate the therapeutic effects of HOXA10-transfected UCMSCs on endometrial injury repair in vivo.

Methods: First, we established T10-UCMSCs (UCMSCs transfected with HOXA10) for transplantation. To establish the endometrial injury model, we injected 95% ethanol into the uterine cavity and transplanted T10-UCMSCs into the uterine cavity from the cornua uteri. Fourteen days later, uteri were collected for histological and biochemical analysis of endometrial growth and receptivity.

Results: Our results showed the endometrial receptivity was better in T10-UCMSCs group than in UCMSCs group, suggesting that HOXA10 could enhance the repairing ability of UCMSCs in the endometrium injury repair. More importantly, the fertility test showed that more embryos were implanted in the T10- UCMSCs group.

Conclusion: Our results suggest that UCMSCs with HOXA10 expression could improve the therapeutic effects on endometrial injury repairing.

Background: It has been observed that bone marrow-derived mesenchymal stem cells (MSCs) migrate towards the injured spinal cord and promote functional recovery when systemically transplanted into the traumatized spinal cord. However, the mechanisms underlying their migration to the spinal cord remain poorly understood.

Methods: In this study, we systemically transplanted GFP- and luciferase-expressing MSCs into rat models of spinal cord injury and examined the role of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis in regulating the migration of transplanted MSCs to the spinal cord. After intravenous injection, MSCs migrated to the injured spinal cord where the expression of SDF-1 was increased. Spinal cord recruitment of MSCs was blocked by pre-incubation with an inhibitor of CXCR4. Their presence correlated with morphological and functional recovery. In vitro, SDF-1 or cerebrospinal fluid (CSF) collected from SCI rats promoted a dose-dependent migration of MSCs in culture, which was blocked by an inhibitor of CXCR4 or SDF-1 antibody.

Results and conclusion: The study suggests that SDF-1/CXCR4 interactions recruit exogenous MSCs to injured spinal cord tissues and may enhance neural regeneration. Modulation of the homing capacity may be instrumental in harnessing the therapeutic potential of MSCs.