Current stem cell research & therapy最新文献

Background: Idiopathic Nephrotic Syndrome (INS) is a common kidney disease in children, and the main clinical manifestations are hypoproteinaemia, proteinuria, hyperlipidaemia, and oedema. Mesenchymal Stem Cells (MSCs) are involved in tissue repair, protection against fibrosis, and immune modulation but have rarely been studied in INS.

Objective: This study aimed to explore the therapeutic potential of stem cells derived from human exfoliated deciduous teeth (SHEDs) in INS using an adriamycin-induced nephropathy (AN) rat model.

Methods: AN was induced in Sprague‒Dawley rats, and SHEDs were transplanted via the tail vein in single (SHED-s) and multidose (SHED-m) regimens. Cell migration assays were used to track the SHED distribution. Weight, urine protein, and serum biochemical assays were also performed. HE and Masson staining were used to observe glomerular and tubular damage, as well as the degree of fibrosis. Immunohistochemistry was used to label T lymphocytes and podocytes, and structural changes in podocytes were observed by electron microscopy. ELISA was used to measure the levels of inflammatory factors. Flow cytometry was used to analyse the balance of Th17 cells and Tregs. The mRNA expression of Th17- and Treg-associated cytokines and specific transcription factors was examined by RT‒PCR.

Results: SHEDs directly migrated to damaged tissues, suggesting a targeted therapeutic effect. SHED transplantation significantly reduced proteinuria and reversed biochemical abnormalities in rats with AN. Both single and multidose SHED treatments could inhibit glomerular and tubular damage and delay the progression of fibrosis caused by adriamycin. SHEDs exerted a protective effect on podocytes. Additionally, this treatment inhibited inflammatory responses and corrected immune imbalances, as evidenced by decreased T lymphocyte infiltration, reduced serum levels of IL-6, TNF-a, and IL-1β, and modulation of the Th17/Treg balance.

Conclusion: In the AN rat model, SHED partly suppressed the development of inflammation and alleviated kidney injury, and immune regulation may be the underlying mechanism.

Introduction: Human adipose-derived stem cells (hADSCs) are considered a promising source for cell replacement therapy in degenerative and traumatic conditions. This study explores the effects of phenylacetate and calcium on the neural differentiation of hADSCs for regenerative medicine. We assessed cell viability and cytotoxicity using the MTT assay, revealing that treatment with 1μM phenylacetate significantly enhanced cell viability compared to control groups over five days, while higher concentrations resulted in cytotoxic effects.

Method: Additionally, qualitative analysis through Acridine orange/ethidium bromide (AO/EB) staining indicated normal cellular characteristics at lower phenylacetate concentrations, whereas higher doses led to observable cell death. A subsequent evaluation of intracellular calcium levels demonstrated a significant increase when hADSCs were treated with both phenylacetate and calcium.

Results: The neural differentiation potential was further assessed through the relative quantification of neuronal-specific genes, showing marked upregulation of NSE, Oligo-2, β-tubulin III, and MAP-2 in all treatment groups compared to controls. Immunohistochemistry confirmed elevated protein expression of neural markers in cultures supplemented with phenylacetate and calcium.

Conclusion: These findings suggest that phenylacetate, particularly in conjunction with calcium, enhances the neural differentiation of hADSCs, highlighting its potential utility in regenerative medicine strategies targeting neurodegenerative conditions.

Introduction: During mesenchymal stem cell (MSCs) aging, a decrease in its proliferation and regenerative capacity occurs, which is implicated in human aging. The MSCs aging process is regulated by genetics, metabolism, the external environment, and various complex pathways.

Method: The aging of MSCs during in vitro culture poses a major challenge for developing cell therapy aimed at combating human diseases and aging. To identify the contributing factors underlying MSCs aging, we obtained datasets of mRNA expression changes before and after aging from the Gene Expression Omnibus (GEO) database and datasets of extracellular vesicles (EVs) microRNAs (miRNAs) expression changes (GSE153752, GSE195634, and GSE226464). We conducted an indepth analysis to screen the correlation between EVs-miRNAs and MSCs aging.

Result: Our analysis identified significant differences in the expression of hsa-miR-146a-5p, hsamiR- 432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p in EVs before and after MSCs aging. These differences arise from the post-MSCs aging activation of signaling pathways, such as FOXO and P53, which promote the expression of hsa-miR-146a-5p, hsa-miR-432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p.

Conclusion: Subsequently, these miRNAs are transported to EVs upon binding to the RNA-binding proteins A2BP1, SFRS2, MBNL1, EIF4B, and ACO1. This study used the correlation between MSCs aging and specific EVs-miRNAs to predict MSCs aging during the culture process.

Introduction/objective: Trigeminal Neuralgia (TN) is an extremely painful condition without an established treatment other than symptom-suppressive medications or temporary relief from corticosteroid injections. Mesenchymal Stem Cells (MSCs) have demonstrated the ability to enhance healing and reduce inflammation and pain without side effects. Our objective was to evaluate the safety and efficacy of CT-guided foramen ovale MSC injection in the treatment of TN.

Methods: A 48-year-old woman presented with a 22-year history of severe TN. Previous treatments, including microvascular decompression, acupuncture, chiropractic adjustment, and hypnotism had failed. Medications decreased pain, but produced severe bothersome mental clouding. After proper informed consent, the patient elected trigeminal nerve injection in the foramen ovale with AlloRx (vitrobiopharma.com Golden Colorado) umbilical cord-derived Mesenchymal Stem Cells (MSCs). An experienced pain specialist with previous experience using CT guidance with sedation to inject the trigeminal nerve in the foramen ovale with corticosteroids performed the injection using 20 million MSCs. The patient reported no adverse events or complications related to the treatment.

Results: At 1 month post-treatment, the patient reported dramatically reduced pain/tingling, and no longer needed medication, which resulted in the resolution of her mental clouding. At 12 months post-treatment, some symptoms recurred, but the patient maintained substantial cognitive improvements and required a reduced dose of medication.

Conclusion: We have demonstrated, for the first time, CT-guided MSC injection into the foramen ovale to result in significant improvement in trigeminal neuralgia without side effects.

Background: Zhengsui Wan (ZSW) is a commonly used traditional Chinese medicine formula for treating Acute Lymphatic Leukemia (ALL) in our institution, and it has shown potential efficacy. However, its mechanism of action (MoA) remains unclear. In this study, we systematically explored the ZSW in ALL (in vitro and in vivo) using network pharmacology and molecular docking techniques.

Methods: Mass spectrometry was conducted to analyze possible active components in ZSW. BALB/c mice were treated by ZSW aqueous decoction, and mesenchymal stem cells (MSCs) were extracted for proteomic analysis to evaluate differentially expressed proteins. Moreover, proteins associated with acute lymphoblastic leukemia in SwissTargetPrediction and GeneCards databases were screened, and they intersected with differentially expressed proteins to obtain potential targets for ZSW. Protein interactions were constructed for the selected targets. Then, we performed GO and KEGG enrichment analysis on its basis and screened the core target through K-core. We validated it by molecular docking with the top three actives in the molecular network in degree value. Finally, we detected the regulation of ICAM1 in MSCs by ZSW by qRT-PCR.

Results: We detected 182 active ingredients in ZSW and identified 725 differential proteins in ZSWtreated mice, of which 25 were potential targets. Furthermore, MMP2, ICAM1, PSEN1, SLC9A1, and MMP14 were identified as core targets using the PPI network and K-core screening. Moreover, ZSW significantly downregulated ICAM1 expression in MSCs. GO and KEGG enrichment analyses showed that the results of ZSW were coordinated through immunomodulatory, inflammation-related, and drug resistance-related genes, including the PI3K-Akt, cAMP, and Wnt signaling pathways. Molecular docking and molecular dynamics simulations indicated moderate binding capacity between the active compounds and the screened target.

Conclusion: In this study, we successfully identified possible active ingredients and predicted potential targets and pathways for ZSW for the treatment of ALL. We provide a new strategy for further research on the molecular basis of ZSW biological effects in ALL. In addition, the potential active ingredients could provide new leads for drug discovery in ALL investigations.

Background: The heavy burden of cardiovascular diseases demands innovative therapeutic strategies dealing with cardiomyocyte loss. Cardiac Stem Cells (CSCs) are renewable cells in the myocardium with differentiation and endocrine functions. However, their functions are significantly inhibited in conditions of severe hypoxia or inflammation. The mechanism of hypoxia affecting CSCs is not clear. Interleukin-6 (IL-6) appears active in both hypoxic and inflammatory microenvironments. The aim of this study was to explore whether IL-6 is related to CSC apoptosis and autophagy under severe hypoxia.

Methods: In this study, rat CSCs were extracted by alternate digestion. The interaction of miR-98 and IL-6 mRNA was detected by the dual luciferase method, and qPCR was applied to confirm the effect of miR-98 on IL-6 expression. The effect of IL-6 on CSC apoptosis was measured by flow cytometry and the effect of IL-6 on CSC autophagy by transmission electron microscopy. The western blot method was applied to detect the effect of IL-6 on the expressions of proteins related to apoptosis and autophagy. ANOVA and Dunnett T3's test were employed in the statistical analysis. When p < 0.05, the difference was significant.

Results: Under severe hypoxia conditions, IL-6 increased CSC apoptosis and decreased p-STAT3 expression significantly. CSC apoptosis increased significantly after inhibition of the STAT3 signaling pathway under severe hypoxia. IL-6 could also significantly inhibit CSCs' autophagy and block their autophagy flow under severe hypoxic conditions. Meanwhile, it was confirmed that miR-98 had a binding site on IL-6 mRNA and miR-98 significantly inhibited IL-6 mRNA expression in CSCs under severe hypoxic conditions.

Conclusion: miR-98/IL-6/STAT3 has been found to be involved in the regulation of CSCs' apoptosis and autophagy under severe hypoxic conditions and there might be a mutual linkage between CSCs' apoptosis and their autophagy.

Aims: The aim of this study was to investigate the role of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in regulating the intestinal type 2 immune response for either protection or therapy.

Background: hUCMSC-Exo was considered a novel cell-free therapeutic product that shows promise in the treatment of various diseases. Type 2 immunity is a protective immune response classified as T-helper type 2 (Th2) cells and is associated with helminthic infections and allergic diseases. The effect of hUCMSC-Exo on intestinal type 2 immune response is not clear.

Method: C57BL/6 mice were used to establish intestinal type 2 immune response by administering of H.poly and treated with hUCMSC-Exo before or after H.poly infection. Intestinal organoids were isolated and co-cultured with IL-4 and hUCMSC-Exo. Then, we monitored the influence of hUCMSC-Exo on type 2 immune response by checking adult worms, the hyperplasia of tuft and goblet cells.

Result: hUCMSC-Exo significantly delays the colonization of H.poly in subserosal layer of duodenum on day 7 post-infection and promotes the hyperplasia of tuft cells and goblet cells on day 14 post-infection. HUCMSC-Exo enhances the expansion of tuft cells in IL-4 treated intestinal organoids, and promotes lytic cell death.

Conclusion: Our study demonstrates hUCMSC-Exo may benefit the host by increasing the tolerance at an early infection stage and then enhancing the intestinal type 2 immune response to impede the helminth during Th2 priming. Our results show hUCMSC-Exo may be a positive regulator of type 2 immune response, suggesting hUCMSC-Exo has a potential therapeutic effect on allergic diseases.

Introduction: Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor β, which remain under strict regulatory scrutiny when it comes to use in patients.

Method: This study reports the previously unexplored effects of KGN stimulation on cartilage- derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration. Our findings demonstrate that KGN treatment significantly increased markers of chondrogenesis, SOX9 and COL2 following 3-10 days of treatment in human CPCs.

Result: KGN treatment also resulted in a significant dose-dependent increase in GAG production in CPCs. The same efficacy was not observed in human marrow-derived stromal cells (BM-MSCs); however, KGN significantly reduced mRNA expression of cell hypertrophy markers, COL10 and MMP13, in BM-MSCs. Parallel to these mRNA expression results, KGN led to a significant decrease in protein levels of MMP-13 both at 0-5 days and 5-10 days following KGN treatment.

Conclusion: In conclusion, this study demonstrates that KGN can boost the chondrogenicity of CPCs and inhibit hypertrophic terminal differentiation of BM-MSCs.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is a leading cause of disability in young adults. Most therapeutic strategies are based on immunosuppressant effects. However, none of the drugs showed complete remission and may result in serious adverse events such as infection. Mesenchymal stem cells (MSCs) have gained much attention and are considered a potential therapeutic strategy owing to their immunomodulatory effects and neuroprotective functions. Experimental autoimmune encephalomyelitis (EAE), a classical animal model for MS, is widely used to explore the efficacy and mechanism of MSC transplantation. This review summarises the therapeutic mechanism of MSCs in the treatment of EAE, including the effects on immune cells (T cells, B cells, dendritic cells, natural killer cells) and central nervous system-resident cells (astroglia, microglia, oligodendrocytes, neurons) as well as various strategies to improve the efficacy of MSCs in the treatment of EAE. Additionally, we discuss the clinical application of MSCs for MS patients as well as the challenges and prospects of MSC transplantation.