Current Stem Cell Research & Therapy - Volume 20, Issue 7, 2025

Alzheimer's disease (AD) is a neurodegenerative disease that is still incurable. Therapy with stem cell or extracellular vesicles is a promising strategy for AD treatment. Therefore, we evaluated whether stem cell-derived extracellular vesicles could improve cognitive function and pathological features in AD model mice.

PubMed, Web of Science, Embase, and The Cochrane Library were searched for studies reporting stem cell-derived extracellular vesicles treatment of AD mice from the establishment of each database to 1^st August 2023. SYRCLE was used to assess the risk of bias. The extracted data were analyzed using RevMan 5.4 and Stata 15 software.

19 studies were included in the analysis. Meta-analysis showed that treatment with stem cell-derived extracellular vesicles significantly improved cognitive performance of AD mice in the Morris water maze test and the novel object recognition test, reduced β-amyloid deposition, alleviated neuroinflammation and decreased levels of the proinflammatory cytokines and glial fibrillary acidic protein (GFAP) in the brain of AD mice. However, stem cell-derived extracellular vesicle did not affect the level of brain phosphorylated tau (p-Tau).

stem cell-derived extracellular vesicles may promote the degradation of β-amyloid plaques in the brain, regulate immunity and protect nerves, which result in cognitive improvement in AD mice.

Spinal Cord Injury (SCI) results in motor, sensory, and autonomic dysfunctions and causes social and economic problems. Surgery, medication, and stem cell transplantation are therapeutic strategies for SCI. The use of endogenous neural stem cells seems preferable due to their lower immune responses. miR-126 serves as a promising microRNA for reducing inflammation after SCI. It can promote angiogenesis and proliferation of neural stem cells.

This study aimed to observe changes in miR-126 expression after SCI in an animal mice model.

A total of 42 healthy adult FVB mice were divided equally into 7 groups (6 SCI model versus 1 control). At different periods following SCI establishment in the model groups, Basso Mouse Scale score (BMS), histopathological changes, and expression levels of miR-126 were evaluated in the model groups compared to the control one.

The BMS score increased to a certain extent as the time after spinal cord injury progressed. HE and Nissl staining showed that the acute period (1-7 days) after spinal cord injury was characterized by neuronal loss, whereas the chronic phase (21^st day) was characterized by scar and cavity formation. Compared with the control group, the model group exhibited decreased expression of miR-126 during the acute phase (days 1-7 post-SCI). However, its expression increased by 21^th day after SCI.

Overexpressed miR-126 can contribute to reduced SCI-related damages, which may result in the promotion of the growth and proliferation of neural stem cells as well as the repair of motor function.

Osteoporotic fracture is a pathological fracture secondary to osteoporosis, causing disabilities and a heavy burden to the patients. In the previous study, we found that salvianolic acid B (SalB) promoted the osteogenesis of Mesenchymal Stem Cells (MSCs).

This study aimed to explore the role of SalB in osteoporotic fracture healing, as well as the potential molecular mechanism.

Human bone marrow mesenchymal stem cells (hMSCs) were treated with SalB or PBS in vitro, and an osteoporotic fracture model in Sprague-Dawley (SD) rats was established successfully. SalB or PBS was locally injected at the fracture. Eight weeks later, microCT was used to compare the healing of osteoporotic fractures with or without SalB. The relative expressions of mRNAs were measured by qRT-PCR. Bioinformatics analysis, RT-PCR, and dual luciferase reporter assay were utilized to detect the interrelation of genes. Immunohistochemistry staining was used to test expressions of proteins.

In the present study, we found that SalB significantly increased the level of lncRNA- MALAT1 in a dose-dependent manner. Additionally, silencing lncRNA-MALAT1 inhibited the expressions of osteogenesis-related marker genes and abolished the effect of SalB on osteogenesis. Also, we found that lncRNA-MALAT1 sponged miR-155-5p, and miR-155-5p directly targeted HIF-1α. Using the osteoporotic fracture healing model, our result demonstrated that local administration of SalB could promote both bone and type H vessel formation in the calluses. The mechanical test further showed that SalB could improve the mechanical properties of fractured femurs.

Taken together, our study reported that SalB could promote osteogenesis and type H vessel formation to accelerate osteoporotic fracture healing through the lncRNA- MALAT1/miR-155-5p/HIF-1α axis.

Nucleus pulposus mesenchymal stem cells play a fatal role in intervertebral disc homeostasis. Magnesium is an essential bioactive element for the human body, regulating intracellular enzyme activity and promoting stem cell adhesion and differentiation.

This study aimed to detect the effects of Mg²⁺ on nucleus pulposus mesenchymal stem cells and explore the mechanism by which magnesium ions promote the differentiation of nucleus pulposus mesenchymal stem cells.

Nucleus pulposus mesenchymal stem cells digested from the caudal intervertebral disc of 3-month-old SD rats were interfered with using different concentrations of magnesium ions, and their levels of migration, adhesion, and differentiation were evaluated by biochemical and molecular indices.

Magnesium ion treatment significantly enhanced the migration and adhesion ability of NPMSCs. Meanwhile, magnesium ion treatment promoted NP differentiation of NPMSCs and the formation of nucleus pulposus precipitates. p-Smad2 immunofluorescence staining demonstrated that the nuclear translocation of p-Smad2 was significantly up-regulated after Mg²⁺ stimulation, while this effect was significantly attenuated by the addition of β1 blocker. In addition, protein quantification experiments demonstrated the same results. These results showed that 10mM magnesium can significantly promote the differentiation of NPMSCs, and its mechanism is related to the integrin receptor and TGF-β signaling pathway.

Mg²⁺ at 10 mM significantly promoted migration and differentiation of NPMSCs by a mechanism related to the integrin-TGF signaling pathway.

Acute Kidney Injury (AKI) is a severe complication of cisplatin-based chemotherapy. Thus, searching for novel therapeutic approaches to reduce system toxicity is vital for improving patient outcomes. The use of stem cells or the paracrine factors released by these cells during cultivation is currently being explored as a potential method for AKI prevention during chemotherapy. However, the conditions of stem cell cultivation considerably affect the composition of paracrine factors released by cells.

In this study, we aimed to investigate the impact of paracrine factors derived from mesenchymal stem cells cultured under hypoxic conditions on the progression of AKI induced by cisplatin.

AKI was induced in mice by intraperitoneal administration of cisplatin with the simultaneous injection of fractions of conditioned medium obtained from the cultivation of mesenchymal stem cells under hypoxic conditions. The survival rate of animals was assessed alongside qRT-PCR implementation to assess gene expression of cytokines.

The total fraction of conditioned medium and >30 kDa fraction had no impact on cisplatin nephrotoxicity in mice. However, either subcutaneous or intraperitoneal administration of <30 kDa fraction of conditioned medium exacerbated animal mortality and led to severe damage to renal tissues. The effect was in a good correlation with KIM-1 and CDKN1A gene expression.

The conditioned medium obtained during mesenchymal stem cells under hypoxic conditions has been found to markedly amplify the toxicity of cisplatin, which should be considered in stem cell therapy of AKI patients.

With the passage of time, the incidence rate of diabetes continues to rise. As a common and serious complication of diabetes, the economic burden of diabetes ulcers is also increasing. However, there is currently no unified clinical treatment strategy for its repair and research, and the treatment effect is not satisfactory. Exosomes derived from MSCs play a crucial role in improving diseases.

This study used the explant culture method to isolate human umbilical cord mesenchymal stem cells (hucMSCs) from Wharton’s jelly, which were identified by flow cytometry and differentiation potential and evaluated tumorigenic potential. The supernatant of P3-P5 cell culture medium was collected and high-concentration human umbilical cord mesenchymal stem cell exosomes (hucMSCs-Exos) were isolated through ultracentrifugation. Qualitatively identified were finished by transmission electron microscopy (TEM), nanosight tracking analysis (NTA) and Western blot (WB). CCK-8 assay and cell scratch experiment were used to evaluate the effects of hucMSCs-Exos on proliferation and migration ability of cells; chicken embryo chorioallantoic membrane experiment (CAM) was used to evaluate the angiogenic effect of hucMSCs-Exos. In order to study the effect of hucMSCs-Exos on diabetes wound healing, type 2 diabetes mellitus (T2DM) mouse model was constructed by a high-fat feeding and a low-dose streptozotocin (STZ) injection. Fasting blood glucose and blood lipids were measured and oral glucose tolerance test (OGTT) was conducted; HucMSCs-Exos were subcutaneously injected into the T2DM wound model mice which were established by a high-fat diet and by a low-dose STZ, and the wound healing was evaluations.

Cells were isolated by explant culture method, and flow cytometry analyses showed that these isolated cells were positive for cells markers CD29, CD90, and CD105, while negative for CD34 and CD45; moreover, these cells could be induced to osteoblasts, adipocytes, and islet-like cells. The tumorigenic experiments showed that these cells have no tumorigenicity. HucMSCs-Exos, separated by ultracentrifugation, displayed spherical or ellipsoidal vesicles with a diameter of around 120 nm, positive for CD9, CD63, and CD81. And they could promote cell proliferation and migration, as well as promote vascular growth (p < 0.01). In vivo experiments showed that hucMSCs-Exos had a promoting effect on wound repair in T2DM mice (p < 0.01).

This study provides a new scheme for the treatment of T2DM ulcer.

Oral mucositis (OM) is a common and debilitating side effect of cancer therapies such as radiotherapy, chemotherapy, hematopoietic cell transplant, or their combinations. This study focused on the reparative effects of human embryonic stem cell-derived mesenchymal stem cells(hESC-MSCs) in OM and possible mechanisms.

An ulcer model was created in the rat buccal mucosa to mimic an in vivo animal model of OM mucosal injury, and hESC-MSCs were injected 48h later to assess their reparative effects. In vitro, the efficacy of hESC-MSCs in regulating apoptosis and proliferation in LPS- or 5-fluorouracil (5-FU)-injured HaCaT cells was studied using a transwell coculture system. Subsequently, the PI3K inhibitor LY24002 was used to assess whether hESC-MSCs regulated injured HaCaT cells through the PI3K/AKT pathway.

In vivo, we found that hESC-MSCs injection promoted OM healing in rats through the acceleration of re-epithelialization and a decrease in apoptosis. In vitro, our findings revealed that the hESC-MSCs treatment led to a reduction in the quantity of HaCaT cells undergoing apoptosis. Western blot analysis revealed that hESC-MSCs activated AKT, resulting in increased protein levels of PCNA and BCL-2 and decreased protein levels of Bax and Caspase-3. Whereas LY294002 reversed these changes.

These findings suggest that hESC-MSCs promoted OM wound healing by stimulating the proliferation of epithelial cells and inhibiting their apoptosis in rat models. Furthermore, hESC-MSCs might mediate the PI3K/AKT pathway to modulate apoptosis/proliferation injured by LPS or 5-FU in HaCaT cells.