Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04883-5
Background Pulmonary arterial hypertension (PAH) is a fatal condition characterized by progressive vascular remodeling in the pulmonary arteries, eventually leading to right heart failure and death. Dysregulated extracellular matrix (ECM) remodeling is central to PAH pathogenesis and represents a potential therapeutic target. Mesenchymal stromal cells (MSCs) have shown promise in preclinical studies; however, the optimal therapeutic window, dosing frequency, and mechanistic basis for their regulation of vascular ECM remain unclear. Methods We employed a monocrotaline (MCT)-induced rat model of PAH to evaluate different MSC treatment regimens, including early administration (day 1 post-MCT), delayed administration (days 7 and 14), and repeated dosing (days 1 and 11). Additionally, we combined in vivo and in vitro approaches to investigate how MSCs modulate the activation of pulmonary arterial adventitial fibroblasts (PAAFs) and influence ECM remodeling. Results Biodistribution studies indicated that MSC retention in lung tissue peaked within 24 h and gradually declined by day 21. A single early dose of MSCs (on day 1) significantly ameliorated PAH progression, increasing the 28-day survival rate, reducing right ventricular systolic pressure (RVSP), improving right ventricular function, and attenuating small pulmonary vascular remodeling, including reductions in medial thickening, excessive muscularization, and collagen deposition. Repeated MSC administration did not provide additional therapeutic benefit. Both in animal models and cell cultures, MSCs effectively suppressed PAAF activation and reduced ECM protein production. This anti-fibrotic effect was mediated via the SOCS3/STAT3 signaling pathway. Conclusions Early single-dose MSC therapy effectively alleviates PAH by suppressing PAAF activation and ECM remodeling through the SOCS3/STAT3 pathway, offering a potential therapeutic strategy for PAH.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04025-3
Background Although mesenchymal stem cells (MSCs) have been proven to be appropriate candidates for the treatment of AKI-CKD, their efficacy is limited and variable. Astilbin (AST) had a protective effect on MSCs from oxidative stress via ROS-scavenging, however, whether it can improve MSCs’ renoprotection and the underlying mechanism need to be elucidated. Methods AST-pretreated MSCs were administered intravenously into the ischemia–reperfusion injury mice models and the renal function, pathological changes and inflammation. Were evaluated. In addition, DARTS, molecular docking, surface plasma resonance(SPR), dual-luciferase reporter gene assay and the ChIP-PCR were utilized to explore the potential signaling pathways through which AST exert renal protective effects on MSCs. Results AST-pretreated MSCs markedly improved kidney function, reduced kidney pathological injury and inflammation in AKI and AKI-CKD mice. RNA-seq results showed that PTGS2 related pathway was significantly up-regulated in MSCs after AST pretreatment. DARTS assay, molecular docking and SPR assay revealed that AST could bind with the transcriptional factor of Kruppel-Like Factor 4(KLF4) protein. The promoter of PTGS2 had the binding and transcriptional activation by KLF4. Furthermore, AST pretreatment promoted the secretion of PGE2 in MSCs. And then the westren blot results showed that the protein levels of CD163 and CD206 were upregulated after coculture in AST-pretreated MSCs, indicating that the polarization of RAW264.7 cells towards M2-like macrophages was induced. Knockdown of PTGS2 reversed the ability of AST-pretreated MSCs in converting macrophages to M2 phenotype and reducing their therapeutic effects on AKI-CKD mice. Conclusion AST pretreatment enhances the efficacy of MSCs on AKI and AKI-CKD mice by inducing of M2-like phenotype polarization in macrophages through the PTGS2-mediated pathway. This approach not only provides a novel strategy to strengthen the capability of MSCs but also helps elucidate the beneficial effects of the Chinese herbal medicine AST.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04093-5
Background Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects. Methods Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats. Results In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery. Conclusions Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261500
Phytochemical investigation of the branches and leaves of Aphanamixis polystachya (Meliaceae) yielded a previously undescribed labdane-type diterpenoid, designated as compound 1, together with known analogues. The structure of the new metabolite was established through comprehensive spectroscopic analysis, including HR-ESI-MS, 1D and 2D NMR (HSQC, HMBC, NOESY), and comparison with literature data. The absolute configuration was assigned by electronic circular dichroism (ECD) calculations. Compound 1 features a 1,4-dien-3-one moiety within a labdane skeleton, a structural motif rarely encountered in the Meliaceae family. All isolates were evaluated for their cytotoxic activities against a panel of human cancer cell lines (HepG2, A549, and MCF-7) using the MTT assay. Compound 1 exhibited moderate inhibitory effects with IC50 values ranging from 18.7 to 32.4 μM, while the positive control doxorubicin showed IC50 values of 0.8–2.1 μM. The discovery of this new diterpenoid expands the chemical diversity of A. polystachya and provides a potential scaffold for further anticancer drug development. However, the moderate potency and low yield (0.002% w/w) highlight the need for semisynthetic or biotechnological production strategies to enable preclinical evaluation.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04883-5
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by progressive vascular remodeling, leading to right heart failure. Dysregulated extracellular matrix (ECM) remodeling is central to PAH pathogenesis. Mesenchymal stromal cells (MSCs) have shown promise, but optimal dosing and mechanisms remain unclear. In a monocrotaline (MCT)-induced rat model, we evaluated early (day 1), delayed (days 7 and 14), and repeated (days 1 and 11) MSC administration. Biodistribution showed peak lung retention at 24 h, declining by day 21. A single early dose significantly improved 28-day survival, reduced right ventricular systolic pressure (RVSP), improved right ventricular function, and attenuated vascular remodeling, including medial thickening, muscularization, and collagen deposition. Repeated dosing provided no additive benefit. MSCs suppressed pulmonary arterial adventitial fibroblast (PAAF) activation and ECM protein production in vivo and in vitro. Mechanistically, MSCs upregulated SOCS3 and inhibited STAT3 signaling. These findings support early single-dose MSC therapy for PAH.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21207
BACKGROUND: Hypoxia preconditioning can increase extracellular vesicles, growth factors, anti-inflammatory and immunosuppressive factors in the parasecretory secretions of mesenchymal stem cells. Exosomes derived from human amniotic mesenchymal stem cells preconditioned with hypoxia are expected to play a better therapeutic role in tissue damage repair. OBJECTIVE: To observe the repair effect of exosomes from human amniotic mesenchymal stem cells preconditioned with hypoxia on radiation-induced submandibular gland epithelial cell damage. METHODS: The passage 3 human amniotic mesenchymal stem cells were divided into two groups: hypoxia and normoxia. They were pretreated with hypoxia (1% O2 by volume) and normoxia (20% O2 by volume) for 48 hours, respectively. Then, normoxic and hypoxic human amniotic mesenchymal stem cell exosomes were extracted from the culture supernatant of human amniotic mesenchymal stem cells by modified ultrahigh-speed centrifugation. The submandibular gland epithelial cells of SD newborn rats were divided into blank control group, radiation control group, normoxia-treated group, and hypoxia-treated group. The submandibular gland epithelial cells were treated with 5 Gy radiation to construct a radiation-induced injury model. The normoxia-treated and hypoxia-treated groups were co-cultured with normoxic or hypoxic exosomes for 3 days. CCK-8 assay was used to detect the proliferation activity of rat submandibular gland epithelial cells; ELISA was used to measure the content of α-amylase in the supernatant; RT-qPCR was used to detect the expression of aquaporin 5 mRNA. RESULTS AND CONCLUSION: The cell proliferation activity in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The cell proliferation activity in the normoxia-treated and hypoxia-treated groups on days 2 and 3 was significantly higher than that in the radiation control group (P < 0.05). The cell proliferation activity in the hypoxia-treated group on day 1 was higher than that in the normoxia-treated group, and showed an increasing trend on days 2 and 3, but there was no statistical difference compared with the normoxia-treated group (P > 0.05). The α-amylase content in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The α-amylase content in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). Compared with the normoxia-treated group, the α-amylase content in the hypoxia-treated group showed an increasing trend, but there was no statistical difference (P > 0.05). The expression of aquaporin 5 mRNA in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The expression of aquaporin 5 mRNA in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). The expression of aquaporin 5 mRNA in the hypoxia-treated group was slightly higher than that in the normoxia-treated group, but there was no statistical difference (P > 0.05). The results indicate that both normoxic and hypoxic preconditioned human amniotic mesenchymal stem cell exosomes have a repair effect on radiation-induced submandibular gland epithelial cell damage, but hypoxic exosomes have no obvious advantage.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21600
BACKGROUND: Combining exosomes with biomaterials such as hydrogels and biological scaffolds enables targeted delivery, providing effective support for damaged tissue and significantly enhancing the therapeutic efficiency of exosomes, thus positively impacting spinal cord injury repair. OBJECTIVE: To review the action mechanisms and research progress of exosomes combined with biomaterials in spinal cord injury. METHODS: Databases including CNKI, PubMed, and Web of Science were searched using the Chinese and English search terms “spinal cord injury, exosomes, hydrogel, biological scaffold, neuroinflammation, oxidative stress, axonal regeneration, angiogenesis.” Based on the inclusion criteria, 106 articles were finally included in this review. RESULTS AND CONCLUSION: Current research focuses on the repair of secondary injury after spinal cord injury, and how to better alleviate the damage caused by secondary injury is a key research question. Exosomes combined with biomaterials treat spinal cord injury mainly through regulating neuroinflammation, promoting axonal regeneration, and alleviating oxidative stress. This approach avoids immune rejection, solves the problem of low bioavailability of exosomes, and provides effective tissue support, thereby alleviating secondary symptoms after spinal cord injury. Most studies on exosome-loaded biomaterials for spinal cord injury are limited to cell and animal experiments, lacking clinical trial data. Future research should focus on further mechanistic studies, safety evaluations, and related clinical trials.