Guangdong Xiangxue Stem Cell Regenerative Medicine Technology Co., Ltd.

Vasogenic edema, caused by the disruption of the blood-brain barrier (BBB), is a significant pathological factor in high-altitude cerebral edema (HACE). Due to the rapid progression and high mortality rate of HACE, prophylactic treatment is important. Mesenchymal stem cell exosomes (MSC-EXO) are increasingly being used in tissue injury repair, and research suggests that appropriate conditioning can enhance the targeted efficacy of exosome therapy. Our in vitro experiments revealed that hypoxia preconditioned MSC-EXO (H-EXO) significantly outperformed normoxic MSC-EXO (N-EXO) in multiple protective aspects. Specifically, H-EXO demonstrated enhanced capacity to mitigate hypoxia-induced aberrant angiogenesis, maintain vascular endothelial cell viability, and suppress ROS accumulation and apoptotic signaling under hypoxic stress. Mechanistic investigation identified miR-125a-5p cargo in H-EXO as a key mediator of RTEF-1 targeted inhibition during hypoxic exposure. In corresponding in vivo studies, H-EXO administration effectively attenuated HACE-induced pathological angiogenesis while maintaining crucial vascular homeostasis markers. The therapeutic effects manifested through three principal aspects: 1) downregulation of RTEF-1/VEGF hyperexpression, 2) modulation of VE-cadherin, SMA, and PDGFRα + β expression to preserve BBB integrity, and 3) concurrent protection of neurovascular functions against HACE-induced damage. This investigation elucidates the miR-125a-5p/RTEF-1 axis as the central mechanism through which hypoxic preconditioning enhances MSC-EXO's endothelial protective properties. Our findings establish H-EXO's multimodal therapeutic potential, demonstrating its capacity to simultaneously inhibit pathological angiogenesis, restore BBB function, and protect neural tissue under hypoxic stress conditions. The study elucidates key mechanisms underlying clinical prevention and management of HACE by delineating H-EXO's preventive mechanisms against hypoxia-induced cerebrovascular injury.

Human umbilical cord mesenchymal stem cells (UCMSCs) are a novel stem-cell source to treat osteoarthritis (OA). Here we investigated the therapeutic effects of UCMSCs injection strategies on knee OA in a rabbit model. Thirty OA rabbits randomly received normal saline, a single dose of 1 × 10⁶ UCMSCs, or three injections of 1 × 10⁶ UCMSCs at 2, 4, 6 weeks. Articular cartilages were collected after 8 weeks. Macroscopic and histological assessments indicated that intra-articular injection of UCMSCs, both single and multiple injection, significantly reduced the formation of periarticular osteophytes and articular cartilage degeneration when compared with the control. Furthermore, both UCMSCs injections increased the expression of chondrogenic markers in the articular cartilage, and reduced the levels of TNF-α and IL-6 in synovium. Micro-CT showed significant reduction of sub-chondral bone degeneration and osteophytes in the multiple-injection group compared to the control and single-injection group. Taken together, intra-articular injection of UCMSCs for OA treatment is safe and effective. Single and multiple injection of UCMSCs had comparable reparative effect on cartilage lesions, while multiple injection of UCMSCs further exerted effect on enhancing subchondral bone volume.

Cerebral palsy (CP) is a movement and posture disorder that affects over 50 million people worldwide. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation has emerged as an attractive therapeutic strategy for CP. The administration route appears to be crucial for hUC-MSC to provide adequate neuroprotection. Wistar rats were given hypoxia-ischemia to make the CP model on postnatal day 5. On postnatal day 21, DiR-labeled hUC-MSC were transplanted into the CP rats by intravenous, intrathecal, and lateral ventricle for cell tracking. Uninfused CP rats served as the negative control. The motor behavioral and pathological alteration was analyzed 11, 25, and 39 days after transplantation to assess motor function, immune inflammation, neurotrophy, and endogenous repair. In vivo imaging tracking techniques revealed that intravenous infusion resulted in fewer transplanted cells in the target brain than intrathecal and lateral ventricle infusion (p＜0.05). Three different routes of hUC-MSC infusion improved the motor function of CP rats (p＜0.05). At 11 days post-infusion, intrathecal infusion outperformed intravenous with a significant neurotrophic and oligodendrocyte maturation effect (p＜0.05). Intrathecal infusion equaled lateral ventricle infusion after 25 days. At 39 days post-infusion, lateral ventricle infusion exceeded intravenous and intrathecal infusion with a significant immunosuppressive effect (p＜0.05). Considering the improved effect and less trauma shown early in the intrathecal infusion, repeated intrathecal administration may ultimately lead to the greatest benefit.