Current stem cell research & therapy最新文献

Background: To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and miR-27 (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI).

Approaches and results: We constructed a HIRI mouse model and pretreated it with an injection of agomir-miR-27-3p, agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+miR-27b mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with miR-27 were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a miR-27 target gene. Furthermore, compared to HIRI+NC mice, HIRI+miR-27 mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, β-catenin, c-Myc, and Cyclin D1.

Conclusion: Our findings reveal the role and mechanism of miR-27 in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with antimiR- 27 might demonstrate better protection against HIRI.

A poor prognosis is associated with pancreatic cancer because of resistance during treatment and early distant metastases. The discovery of cancer stem cells has opened up novel avenues for research into the biology and treatment of cancer. Many investigations have pointed out the role of these types of stem cells in the oncogenesis and progression of hematologic and solid malignancies, specifically. Due to the existence of cancer stem cells in the proliferation and preservation of pancreatic tumors, such malignancies could be difficult to eradicate using conventional treatment techniques like chemotherapy and radiotherapy. It is hypothesized that pancreatic malignancies originate from a limited population of aberrant cancer stem cells to promote carcinogenesis, tumour metastasis, and therapeutic resistance. This review examines the role of pancreatic cancer stem cells in this disease and their significance in carcinogenesis, as well as the signals which modulate them, and also examines the ongoing clinical studies that are now being conducted with pancreatic stem cells.

In the past decades, scientists have made outstanding efforts to treat diabetes. However, diabetes treatment is still far from satisfactory due to the complex nature of the disease and the challenges encountered in resolving it. Inflammatory factors are key regulators of the immune system's response to pathological insults, organ neogenesis, rejuvenation of novel cells to replace injured cells and overwhelming disease conditions. Currently, the available treatments for type 1 diabetes include daily insulin injection, pancreatic beta cell or tissue transplantation, and gene therapy. Cell therapy, exploiting differentiation, and reprogramming various types of cells to generate pancreatic insulin-producing cells are novel approaches for the treatment of type 1 diabetes. A better understanding of the inflammatory pathways offers valuable and improved therapeutic options to provide more advanced and better treatments for diabetes. In this review, we investigated different types of inflammatory factors that participate in the pathogenesis of type 1 diabetes, their possible dual impacts on the differentiation, reprogramming, and fusion of other stem cell lines into pancreatic insulin-producing beta cells, and the possibility of applying these factors to improve the treatment of this disease.

Background: Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis.

Objectives: The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage.

Methods: Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (10⁶ cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted.

Results: BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs.

Conclusion: The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Treating chronic wounds is a common and costly challenge worldwide. More advanced treatments are needed to improve wound healing and prevent severe complications such as infection and amputation. Like other medical fields, there have been advances in new technologies promoting wound healing potential. Regenerative medicine as a new method has aroused hope in treating chronic wounds. The technology improving wound healing includes using customizable matrices based on synthetic and natural polymers, different types of autologous and allogeneic cells at different differentiation phases, small molecules, peptides, and proteins as a growth factor, RNA interference, and gene therapy. In the last decade, various types of wound dressings have been designed. Emerging dressings include a variety of interactive/ bioactive dressings and tissue-engineering skin options. However, there is still no suitable and effective dressing to treat all chronic wounds. This article reviews different wounds and common treatments, advanced technologies and wound dressings, the advanced wound care market, and some interactive/bioactive wound dressings in the market.

Mesenchymal stem/stromal cells (MSCs) have exhibited potential for treating multiple inflammation- related diseases (IRDs) due to their easy acquisition, unique immunomodulatory and tissue repair properties, and immune-privileged characteristics. It is worth mentioning that MSCs release a wide array of soluble bioactive components in the secretome that modulate host innate and adaptive immune responses and promote the resolution of inflammation. As the first line of defense, macrophages exist throughout the entire inflammation process. They continuously switch their molecular phenotypes accompanied by complementary functional regulation ranging from classically activated pro-inflammatory M1-type (M1) to alternatively activated anti-inflammatory M2-type macrophages (M2). Recent studies have shown that the active intercommunication between MSCs and macrophages is indispensable for the immunomodulatory and regenerative behavior of MSCs in pharmacological cell therapy products. In this review, we systematically summarized the emerging capacities and detailed the molecular mechanisms of the MSC-derived secretome (MSC-SE) in immunomodulating macrophage polarization and preventing excessive inflammation, providing novel insights into the clinical applications of MSC-based therapy in IRD management.

Background: Mesenchymal stem cells (MSCs)-derived exosomes have been previously demonstrated to promote tissue regeneration in various animal disease models. This study investigated the protective effect of exosome treatment in carbon tetrachloride (CCl4)-induced acute liver injury and delineated possible underlying mechanism.

Methods: Exosomes collected from conditioned media of previously characterized human umbilical cord-derived MSCs were intravenously administered into male CD-1 mice with CCl₄-induced acute liver injury. Biochemical, histological and molecular parameters were used to evaluate the severity of liver injury. A rat hepatocyte cell line, Clone-9, was used to validate the molecular changes by exosome treatment.

Results: Exosome treatment significantly suppressed plasma levels of AST, ALT, and pro-inflammatory cytokines, including IL-6 and TNF-α, in the mice with CCl₄-induced acute liver injury. Histological morphometry revealed a significant reduction in the necropoptic area in the injured livers following exosome therapy. Consistently, western blot analysis indicated marked elevations in hepatic expression of PCNA, c-Met, Ets-1, and HO-1 proteins after exosome treatment. Besides, the phosphorylation level of signaling mediator JNK was significantly increased, and that of p38 was restored by exosome therapy. Immunohistochemistry double staining confirmed nuclear Ets-1 expression and cytoplasmic localization of c-Met and HO-1 proteins. In vitro studies demonstrated that exosome treatment increased the proliferation of Clone-9 hepatocytes and protected them from CCl4-induced cytotoxicity. Kinase inhibition experiment indicated that the exosome-driven hepatoprotection might be mediated through the JNK pathway.

Conclusion: Exosome therapy activates the JNK signaling activation pathway as well as up-regulates Ets-1 and HO-1 expression, thereby protecting hepatocytes against hepatotoxin-induced cell death.

Background: Transplantation of stem cells/scaffold is an efficient approach for treating tissue injury including full-thickness skin defects. However, the application of stem cells is limited by preservation issues, ethical restriction, low viability, and immune rejection in vivo. The mesenchymal stem cell conditioned medium is abundant in bioactive functional factors, making it a viable alternative to living cells in regeneration medicine.

Methods: Nasal mucosa-derived ecto-mesenchymal stem cells (EMSCs) of rats were identified and grown in suspension sphere-forming 3D culture. The EMSCs-conditioned medium (EMSCs-CM) was collected, lyophilized, and analyzed for its bioactive components. Next, fibrinogen and chitosan were further mixed and cross-linked with the lyophilized powder to obtain functional skin patches. Their capacity to gradually release bioactive substances and biocompatibility with epidermal cells were assessed in vitro. Finally, a full-thickness skin defect model was established to evaluate the therapeutic efficacy of the skin patch.

Results: The EMSCs-CM contains abundant bioactive proteins including VEGF, KGF, EGF, bFGF, SHH, IL-10, and fibronectin. The bioactive functional composite skin patch containing EMSCs-CM lyophilized powder showed the network-like microstructure could continuously release the bioactive proteins, and possessed ideal biocompatibility with rat epidermal cells in vitro. Transplantation of the composite skin patch could expedite the healing of the full-thickness skin defect by promoting endogenous epidermal stem cell proliferation and skin appendage regeneration in rats.

Conclusion: In summary, the bioactive functional composite skin patch containing EMSCs-CM lyophilized powder can effectively accelerate skin repair, which has promising application prospects in the treatment of skin defects.