Currently, spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service. The prevention, treatment, and rehabilitation of spinal cord injury have become an important topic in the field of medicine. Therefore, it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.

To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury, and based on the current status of clinical translation, to put forward a few thoughts and outlooks on their clinical use.

The first author searched CNKI and PubMed databases using “mesenchymal stem cells, exosomes, spinal cord injury, miRNA, pathophysiology, clinical translation, clinical trials, good manufacturing practice” as Chinese and English search terms. The types of literature included treatises and reviews, and the language types were English and Chinese. Finally, 72 papers were screened and analyzed.

(1) This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs. A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins, repressing RAS homologous gene family member A, activating cyclophosphoadenosine effector-binding proteins, and signaling and transcriptional activation proteins 3, and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways. Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1, expression of interferon regulatory factor 5, Toll-like receptor 4/nuclear factor-kappa B pathway, and down-regulating related pro-inflammatory factors. Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2. (2) Further comparative analyses revealed that miR-216-5p, miR-145-5p, and miR-146b improved inflammatory responses by regulating related pathways. Combining these miRNAs may produce more significant effects; hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy. (3) There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury, which is related to the need to meet good manufacturing practices before they can be put into clinical use. Challenges such as the need for large-scale, high-volume cell production, the lack of an efficient and uniform method for isolating exosomes, and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry. (4) miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury, and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

Hematopoietic stem cell transplantation is a widely used treatment method to cure malignant and nonmalignant diseases originated from hematological cells. Mobilization and collection of sufficient hematopoietic stem cells are the preconditions to ensure rapid and sustained hematopoietic reconstitution after hematopoietic stem cell transplantation. However, the most commonly used granulocyte colony-stimulating factor with or without chemotherapy still has a mobilization failure rate of 10% to 40%.

To review the present status of hematopoietic stem cell mobilization in recent years, analyze the advantages and disadvantages of different mobilization plans, and be looking forward for new mobilization methods.

Using “hematopoietic stem cell, hematopoietic stem cell transplantation, hematopoietic stem cell mobilization, cytokines, thrombopoietin, CXCR4 antagonists, integrin antagonist, chemotherapy, mobilization efficiency” as Chinese and English keywords, articles published from 1990 to 2024 were searched on CNKI, PubMed, and WanFang databases. A total of more than 300 articles were retrieved, and 68 articles were finally included.

More and more studies have found that granulocyte colony-stimulating factor combined with other agents including plerixafor, interleukins, thrombopoietin, and integrin antagonist could improve hematopoietic stem cell mobilization. Combined use can reduce the dose of granulocyte colony-stimulating factor and related adverse reactions. Some new drugs, such as soluble recombinant FLT3-ligand (CDX-301) and dual α9β1/α4β1 integrin inhibitor BOP, can be combined with granulocyte colony-stimulating factor to promote hematopoietic stem cell mobilization. In addition, some potential mobilization targets, such as prostaglandin E2 receptor and sphingosine 1-phosphate, are still in the research stage. In addition to inherent patient characteristics and treatment options, incorporating biomarkers into the factors affecting mobilization and developing new predictive models will help to effectively predict the failure of hematopoietic stem cell mobilization and improve stem cell mobilization technology.

Numerous studies have indicated that pyroptosis plays a key role in the progression of cancer. In recent years, research has shown that pyroptosis is inextricably linked to the occurrence, development, and treatment of breast cancer. The development of effective pyroptosis-based therapeutic strategies has become a hot topic in the field of breast cancer treatment.

To comprehensively analyze the mechanisms of pyroptosis, explore the role of pyroptosis in the anti-tumor effects in breast cancer, and its potential application value in clinical treatment.

Using English search terms “pyroptosis, breast cancer, inflammasome, gasdermin, caspase, drug resistance, treatment”, PubMed database was searched for articles published from inception to August 2024. Through the preliminary screening of reading titles and abstracts, literature with poor relevance to the research content, outdated information, repeated views, and lack of authority was excluded. Finally, 121 articles were included for review.

Pyroptosis is a special form of programmed cell death that is carried out by the activation of the gasdermin family of proteins, showing potential application value in the treatment of breast cancer. Long-term or improper treatment can lead to drug resistance in cancer cells; research on the mechanism of pyroptosis helps to overcome resistance deficiencies. Pyroptosis can trigger immunogenic cell death, promoting the release of tumor-specific antigens, thereby activating the immune system and enhancing its ability to recognize and clear tumor cells. The expression levels of pyroptosis-related genes can serve as prognostic indicators for breast cancer, helping to assess patients’ treatment responses and survival periods. Research on the mechanisms of pyroptosis can provide new strategies for the treatment of breast cancer, such as targeted drugs and therapeutic methods that induce pyroptosis, contributing to the realization of personalized treatment plans for breast cancer.

Radiotherapy for head and neck tumors can easily cause xerostomia, seriously affecting the quality of life of patients. In recent years, engineered stem cells and their paracrine factors have shown therapeutic potential in the repair of salivary gland injury. However, there is currently no experimental study on the application of amniotic mesenchymal stem cell-derived exosome in radiation-induced salivary gland injury.

To preliminarily explore the repair effect of exosome derived from human amniotic mesenchymal stem cells on radiation-induced submandibular gland injury.

Human amniotic mesenchymal stem cell exosomes were extracted and identified by ultrafiltration and ultracentrifugation. SD rats were randomly divided into a control group, a radiation injury group, and a radiation injury+exosome group. An in vitro model of radiation-induced submandibular gland injury was constructed using the submandibular gland tissue of SD rats irradiated with 18 Gy of radiation. One day after radiation modeling, exosome derived from human amniotic mesenchymal stem cells was injected into the submandibular gland in situ. Samples are taken at 1, 3, 7, and 14 days to detect the resting salivary flow rate. The structure of the submandibular gland tissue was observed by hematoxylin-eosin staining. The expression of glycogen particles in the submandibular gland tissue was observed by Periodic Acid-Schiff staining. Fibrosis in the submandibular gland tissue was observed by Masson staining. The secretion of salivary amylase was detected by enzyme-linked immunosorbent assay. The expression of aquaporin and tight junction proteins in submandibular gland tissue was observed by immunofluorescence staining. Real-time fluorescence quantitative PCR was used to detect the relative expression levels of aquaporins and salivary amylase mRNA in submandibular gland tissue. TUNEL assay was used to detect the apoptosis rate of submandibular gland tissues in each group.

After radiomodeling, compared with the radiation injury group, (1) hematoxylin-eosin staining observed that the submandibular gland tissue structure in the radiation injury+exosome group was restored, the nucleoli increased, the number of acinus increased, and the acinar atrophy improved. (2) Glycogen staining observed that the number and density of positive zymogen granules in the acinar cytoplasm of the radiation injury+exosome group gradually increased. (3) Masson staining results observed that the number and density of positive collagen fibers in the interstitium and around the ducts in the radiation injury+exosome group gradually decreased, the degree of fibrosis decreased, and the collagen deposition decreased. (4) The salivary flow rate in the radiation injury+exosome group increased (P < 0.05). The fluorescence intensity of aquaporin-5 was enhanced (P < 0.05) and the gene expression was significantly enhanced (P < 0.01). The fluorescence distribution of tight junction protein 4 was weakened and the fluorescence intensity decreased (P < 0.05, P < 0.01). The content of salivary amylase increased (P < 0.05) and gene expression were significantly increased (P < 0.01). The number of positive apoptotic cells decreased (P < 0.05, P < 0.01). It is indicated that local injection of exosome derived from human amniotic mesenchymal stem cells could improve the pathological morphology of submandibular gland tissue, promote saliva flow rate and amylase expression, and may play a functional repair role in radioactive submandibular gland injury by inhibiting acinar apoptosis.

Remyelination in the central nervous system is a basic repair process triggered by demyelinating events, mainly through the proliferation, migration, and differentiation of oligodendrocyte precursor cells into oligodendrocytes. The process of remyelination is affected by many factors such as astrocytes, myelin debris, microglia, macrophages, endothelial cells, pericytes, T cells, and age.

Astrocytes play an important role in regulating synaptic activity, nutritional support, and tissue repair in the central nervous system. This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.

A search was conducted on relevant literature collected from CNKI, PubMed, and Web of Science from 2014 to 2024. The search terms were “astrocytes, oligodendrocyte precursor cells, remyelination” in both Chinese and English. Finally, 66 articles were included after screening and summarized.

(1) The treatment of demyelinating diseases, such as multiple sclerosis, is limited to disease-modifying therapies, and there is no available method to overcome the failure of remyelination. Therefore, it is necessary to explore targets related to remyelination to promote myelin repair. (2) Remyelination is a process in which oligodendrocyte precursor cells proliferate, migrate, differentiate, and mature into oligodendrocytes, and the latter produce myelin to wrap axons to form myelin sheath. (3) Astrocytes regulate remyelination by phagocytosis of myelin debris, participating in inflammatory response, transforming into oligodendrocyte lineage cells, providing energy supply for oligodendrocyte lineage cells, releasing neurotrophic factors, and secreting extracellular matrix components. (4) The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination. Some drugs have satisfactory effects, but their effectiveness and safety still need more basic research and clinical trials to verify. (5) The mechanism of action of astrocytes in remyelination has not been fully elucidated, and the related molecular targets and signaling pathways can be further studied.

Osteoarthritis is a progressive joint condition identified by ongoing deterioration of the cartilage matrix, and there is currently no effective drug treatment plan. Metformin-modified exosomes isolated from bone marrow-derived mesenchymal stem cells can become a new method for treating osteoarthritis due to their avoidance of oral drug adverse reactions and immunogenicity.

To study the controlling impact of exosomes from metformin-altered bone marrow-derived mesenchymal stem cells on chondrocytes.

Rabbit bone marrow-derived mesenchymal stem cells and chondrocytes were cultured in vitro. Bone marrow-derived mesenchymal stem cells derived exosomes and metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes were collected using a high-speed centrifuge. Chondrocytes were cultured with exosome-containing culture medium for 24 hours and then treated with 100 µmol/L H₂O₂ for 24 hours. The capability changes of two extracellular vesicles on chondrocyte proliferation and migration were detected using CCK8 assay and scratch healing experiment, respectively. Western blot analysis and RT-qPCR were employed to examine the alterations in the expression of type II collagen, P16 protein, and their mRNA in chondrocytes.

Western blot analysis was utilized to assess the changes in the expression of MKK7/JNK pathway proteins. ELISA kits were utilized to measure the activity of cell superoxide dismutase and the levels of malondialdehyde in chondrocytes.

(1) In an oxidative stress environment, the proliferation and migration abilities of chondrocytes were weakened. The two types of exosomes could restore the proliferation and migration abilities of chondrocytes to a certain extent. Metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes had a significantly better improvement effect (P < 0.05). (2) Compared with normal bone marrow mesenchymal stem cell-derived exosomes, metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes could more effectively increase type II collagen expression and superoxide dismutase activity (P < 0.05), and were also more effective in reducing P16 expression and malondialdehyde levels (P < 0.05). (3) The two types of exosomes could inhibit the expression of MKK7 and p-JNK proteins to a certain extent, and the inhibitory effect of metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes was more significant (P < 0.05). The results show that in an oxidative stress environment, metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes resist chondrocyte aging and promote chondrocyte proliferation by inhibiting the MKK7/JNK pathway.

With aging, the regenerative capacity and differentiation function of bone marrow mesenchymal stem cells progressively decline, reducing bone tissue repair efficacy. Thus, identifying bone marrow mesenchymal stem cell subpopulations with enhanced osteogenic potential is of significant importance for advancing bone tissue engineering.

To evaluate the osteogenic differentiation potential differences between STRO-1 positive and negative bone marrow mesenchymal stem cells under osteogenic induction conditions.

SD rat bone marrow mesenchymal stem cells were isolated and cultured. The expression of CD29, CD45, CD90, and STRO-1 was identified via flow cytometry and immunofluorescence. Immunomagnetic cell sorting was used to separate STRO-1 positive and negative bone marrow mesenchymal stem cells. The cells of two groups were subjected to osteogenic induction for 7 and 14 days. qRT-PCR and western blotting were performed to analyze differences in osteogenesis-related gene expression (Collagen I, Runt-related transcription factor 2, osteoprotegerin, and osteocalcin) and protein levels. Alizarin red staining and alkaline phosphatase staining were used to observe calcium nodule formation.

Flow cytometry showed high expression levels of CD29 and CD90 and low expression of CD45, with a positive STRO-1 expression rate of 12.8%. Immunofluorescence results were consistent with those of flow cytometry. After magnetic cell sorting, STRO-1 positive cells demonstrated a higher colony formation rate than STRO-1 negative cells. On day 14, STRO-1 positive cells showed significantly higher osteogenic differentiation potential than on day 7, with significantly elevated osteogenesis-related marker levels compared to STRO-1 negative cells (P < 0.01). The findings indicate that STRO-1 positive bone marrow mesenchymal stem cells exhibit significant advantages in osteogenic potential, providing a theoretical basis for their selection as ideal seed cells in bone tissue engineering. In future applications, they may represent a promising therapeutic approach for bone defect repair.

Exosomes have been confirmed to be closely related to cartilage degeneration in osteoarthritis. However, the role and mechanism of exosome-derived genes in cartilage degeneration of osteoarthritis have not been fully elucidated.

Bioinformatics analyses were used to screen the genes related to cartilage degeneration in the synovial exosomes of patients with osteoarthritis, and to determine their biological functions and signaling pathways in order to provide new therapeutic targets for delaying cartilage degeneration in osteoarthritis.

Firstly, osteoarthritis-related exosome dataset GSE185059 and cartilage degeneration dataset GSE114007 were downloaded from Gene Expression Omnibus (GEO) database to screen exosome-derived cartilage degeneration related genes. GO functional and KEGG pathway enrichment analyses were performed based on the screened exosome-derived cartilage degeneration related genes. Protein-protein interaction network was drawn and Ingenuity Pathway Analysis (IPA) was conducted to screen and obtain key exosome-derived cartilage degeneration-related genes. Finally, qRT-PCR was used to verify the expression of key genes in osteoarthritis cartilage tissue and interleukin-1β stimulated chondrocyte models.

(1) There were 831 differentially expressed genes in the GSE185059 dataset and 5 323 differentially expressed genes in the GSE114007 dataset. A total of 94 exosome-derived cartilage degeneration related genes were screened after the intersection of these differentially expressed genes, of which 51 genes were down-regulated and 43 genes were up-regulated. (2) GO functional enrichment analysis showed that the up-regulated genes were mainly involved in the positive regulation of cell-cell adhesion, the positive regulation of T cell activation, and chronic inflammatory response, while the down-regulated genes were mainly involved in biological processes such as cell aggregation, cartilage differentiation and development, and skeletal system morphogenesis. (3) KEGG pathway enrichment analysis showed that exosome-derived cartilage degeneration-related genes were mainly involved in tryptophan enrichment metabolism, vitamin B6 metabolism, and leukocyte transendothelial migration. (4) The constructed protein-protein interaction network confirmed the existence of multiple interaction relationships among exosome-derived cartilage degeneration-related genes. Combined with five algorithms in CytoHubba software, four key exosome-derived cartilage degeneration-related genes were further screened, namely THY1, CYP1A1, NFKB2, and COL6A3. (5) The results of qRT-PCR showed that compared with normal cartilage, the expressions of THY1 and COL6A3 in osteoarthritic cartilage were increased, while the expression of CYP1A1 and NFKB2 was decreased. Similarly, compared with the unstimulated group, the expression of THY1 and COL6A3 in the interleukin-1β induced chondrocytes was upregulated, while the expression of CYP1A1 and NFKB2 was downregulated. (6) These results indicate that THY1, CYP1A1, NFKB2, and COL6A3 are genes related to cartilage degeneration in the exosomes of synovial fluid of patients with osteoarthritis, and may participate in the pathogenesis of osteoarthritis by regulating biological processes such as protein tyrosine kinase activity and lipid metabolism, as well as nuclear factor-κB signaling pathway and focal adhesion signaling pathway. However, the specific regulatory roles and molecular mechanisms of these key genes in cartilage degeneration need to be further verified by experiments.

Premature ovarian failure has manifested a trend of younger, and stem cell therapy has been progressively implemented in clinical practice in recent years. Nevertheless, given the extensive range of sources and variegated existence of stem cells in diverse tissues, certain disparities prevail in their biological characteristics and functions. In this paper, the therapeutic efficacies of dissimilar sources of mesenchymal stem cells on animal models of premature ovarian failure were contrasted, with the aim of providing a basis for the clinical application of stem cells.

The animal model experiments of mesenchymal stem cell therapy for premature ovarian failure were retrieved from PubMed, The Cochrane Library, and EMbase, as well as Chinese databases such as CNKI, WanFang, VIP, and China Biomedical Literature Service. The search period extended from the inception to December 31, 2023. Two researchers independently screened the literature, extracted and analyzed the data. The quality of the included studies was evaluated by means of the SYRCLE animal experiment bias risk assessment table. Main outcome measures: Follicle stimulating hormone, estradiol, luteinizing hormone, the quantity of follicles at all levels. Secondary outcome measure: Pregnancy rate. Network meta-analysis, mapping, and tabulation were executed using Stata 17.0 software after assessing the risk of bias in the included studies.

Totally 24 animal experiment studies were incorporated, and the overall quality of the literature was mediocre, encompassing 7 distinct sources of mesenchymal stem cells. They were umbilical cord-derived mesenchymal stem cells, menstrual blood-derived mesenchymal stem cells, placenta-derived mesenchymal stem cells, human cord blood-derived mesenchymal stem cells, bone marrow-derived mesenchymal stem cells, adipose-derived mesenchymal stem cells, and amnio-derived mesenchymal stem cells. The network meta-analysis demonstrated that (1) in contrast to the blank group, mesenchymal stem cells from various sources were effective in enhancing the pregnancy rate and estradiol, reducing follicle-stimulating hormone and luteinizing hormone, augmenting the number of follicles at all levels, and diminishing the number of atretic follicles. (2) According to the area map under the cumulative sequencing curve, the three stem cells with the most prominent efficacy in improving estradiol levels were umbilical cord-derived mesenchymal stem cells (72.7%) > adipose-derived mesenchymal stem cells (72.6%) > menstrual blood-derived mesenchymal stem cells (71.7%). (3) The three kinds of stem cells with the highest efficacy in reducing follicle-stimulating hormone levels were the adipose-derived mesenchymal stem cells (96.3%) > human cord blood-derived mesenchymal stem cells (65.4%) > umbilical cord-derived mesenchymal stem cells (63.9%). (4) The three kinds of stem cells with the highest efficacy in reducing luteinizing hormone levels were adipose-derived mesenchymal stem cells (100.0%) > umbilical cord-derived mesenchymal stem cells (51.6%) > human cord blood-derived mesenchymal stem cells (46.8%). (5) The top three kinds of stem cells for increasing the number of primordial follicles were human cord blood-derived mesenchymal stem cells (76.3%) > umbilical cord-derived mesenchymal stem cells (75.5%) > menstrual blood-derived mesenchymal stem cells (57.5%). (6) The top three kinds of stem cells for increasing the number of primary follicles were umbilical cord-derived mesenchymal stem cells (75.3%) > adipose-derived mesenchymal stem cells (53.0%) > the placenta-derived mesenchymal stem cells (51.7%). (7) The top three kinds of stem cells for increasing the number of secondary follicles were adipose-derived mesenchymal stem cells (76.1%) > menstrual blood-derived mesenchymal stem cells (66.8%) > umbilical cord-derived mesenchymal stem cells (66.5%). (8) The top three kinds of stem cells in reducing the number of atretic follicles were adipose-derived mesenchymal stem cells (99.9%) > bone marrow-derived mesenchymal stem cells (68.1%) > umbilical cord-derived mesenchymal stem cells (53.4%).

(1) For animal models of premature ovarian failure, the results of the network meta-analysis disclosed that various stem cell transplantation treatments were preponderant over the blank or placebo group to varying extents, and the efficacies were comparable. (2) The results indicated that umbilical cord-derived mesenchymal stem cells were the most frequently utilized and adipose-derived mesenchymal stem cells were the most potent. More high-quality experimental study data are requisite in the future for further validation.

Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome, but the specific mechanism is not yet clear.

To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.

A total of 70 SD rats were randomly divided into a normal control group (n=10), a model group (n=15), a western medicine group (n=15), a low-dose Huosui Formula group (n=15), and a high-dose Huosui Formula group (n=15). Except for the normal control group, the other four groups were injected with dimethylbenzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models. After modeling, the normal control group and the model group were given normal saline; the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg, and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula, respectively, by intragastric administration once a day for 28 consecutive days. Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation. Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.

(1) Compared with the normal control group, peripheral blood leukocyte, neutrophil, hemoglobin, platelet, and CD4⁺, CD4⁺/CD8⁺ levels were decreased in the model group significantly (P < 0.05), while CD4⁺PD-1⁺, CD8⁺PD-1⁺, CD4⁺CTLA-4⁺, and CD8⁺CTLA-4⁺ expressions were significantly upregulated (P < 0.05). (2) In all dosage groups, myelopoietic proliferation was increased compared with the model group, with no significant difference between the groups (P > 0.05). (3) Compared with the model group, leukocytes, hemoglobin, platelets, and CD4⁺, CD4⁺/CD8⁺ were significantly elevated in the high-dose Huosui Formula group (P < 0.05), the expression of CD8⁺ was significantly lower (P < 0.05), and the levels of CD4⁺PD-1⁺, CD8⁺PD-1⁺, CD4⁺CTLA-4⁺, and CD8⁺CTLA-4⁺ were down-regulated but not statistically significant (P > 0.05). (4) The western medicine group and the high-dose Huosui Formula group showed similar efficacy. The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group. These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats, increase the levels of CD4⁺, and CD4⁺/CD8⁺ while down-regulate the expression levels of CD4⁺PD-1⁺, CD8⁺PD-1⁺, CD4⁺CTLA-4⁺, and CD8⁺CTLA-4⁺. These observations suggest a link to the negative immunoregulation mechanism.