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.

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.

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.

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.

Currently, the treatment methods for colorectal cancer include surgical resection and chemotherapy. However, the subsequent quality of life of patients cannot be improved due to the multiple surgical complications and drug resistance in the later stage of chemotherapy.

To review the mechanism of action, latest progress and existing problems of exosomes derived from mesenchymal stem cells in the treatment of colorectal cancer.

PubMed, CNKI and WanFang databases were searched for relevant literature using the search terms of “mesenchymal stem cells exosomes, colorectal cancer, chemotherapy, treatment” in Chinese and English, respectively. Finally, 96 articles were included for analysis.

(1) Mesenchymal stem cell-derived exosomes play different roles in the treatment of colorectal cancer mainly through the microRNAs and long-chain non-coding RNAs carried by themselves to mediate different signaling pathways. (2) Mesenchymal stem cell-derived exosomes are highly stable and biocompatible, which makes them excellent carriers of therapeutic drugs. (3) Mesenchymal stem cell-derived exosomes have different effects on resistance to different types of chemotherapeutic agents.