Mesenchymal stem cells (MSCs) are multipotent stem cells characterized by their robust proliferative capacity, homing ability, differentiation potential, and low immunogenicity in vitro. MSCs can be isolated from a variety of tissues, primarily including but not limited to bone marrow, adipose tissue, umbilical cord, placenta, and dental pulp. Although there have been a large number of clinical studies on the treatment of diseases by MSCs and MSCs-derived exosomes (MSCs-EXO), the large-scale clinical application of MSCs and MSCs-EXO have been limited due to the heterogeneity of the results among various studies. This review provides a detailed description of the classification and characterization of MSCs and MSCs-EXO, as well as their extraction methods. Furthermore, this review elaborates on three key mechanisms of MSCs and MSCs-EXO: paracrine mechanisms, immunomodulatory and anti-inflammatory effects, as well as their promotion of tissue regeneration. This review also examines the role of MSCs and MSCs-EXO in cardiovascular diseases, neurological disorders, autoimmune diseases, musculoskeletal disorders, and other systemic diseases over the past five years, while discussing the challenges and difficulties associated with their clinical application. Finally, we systematically summarized and analyzed the potential causes of the various heterogeneous results currently observed. Additionally, we provided an in-depth discussion on the challenges and opportunities associated with the clinical translation of disease treatment approaches based on MSCs, MSCs-EXO, and engineered exosomes.

Background: Disorders of consciousness (DoC) following severe brain injury pose significant diagnostic and therapeutic challenges. This narrative review comprehensively examines the current evidence for neuromodulation techniques in promoting consciousness recovery, including their mechanisms, efficacy, and future directions. Methods: We conducted a narrative review of evidence from randomized controlled trials, meta-analyses, and pilot studies investigating non-invasive and minimally invasive neuromodulation techniques for DoC. PubMed, Web of Science, Embase, CNKI, and Wanfang databases were searched from inception through December 2025. Techniques reviewed include transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), median nerve stimulation (MNS), transcutaneous auricular vagus nerve stimulation (taVNS), transcranial focused ultrasound (tFUS), acupuncture, and spinal cord stimulation (SCS). Results: High-frequency repetitive TMS (10–20 Hz) targeting the dorsolateral prefrontal cortex showed significant CRS-R improvements with sustained effects. Right MNS (8 h/day, 2 weeks) significantly increased consciousness recovery rates in acute traumatic brain injury (RR = 1.36, 95% CI 1.18–1.56). Anodal tDCS demonstrated modest benefits, particularly in MCS patients. taVNS improved consciousness in MCS but not UWS patients. Short-term SCS (70 Hz) produced sustained improvements, especially in MCS − patients. Preliminary tFUS studies targeting the thalamus showed promising results. Combined interventions exhibited synergistic effects. Treatment responses varied by consciousness level, etiology, and individual factors. Adverse events were minimal across modalities. Conclusion: Emerging evidence suggests that neuromodulation may have therapeutic potential for DoC, with comparatively stronger support currently available for high-frequency rTMS, right MNS, and SCS. Future research should prioritize large-scale RCTs, predictive biomarker identification, personalized closed-loop protocols, and optimal combination strategies, with a gradual shift from deterministic to individualized treatment paradigmss.

Background/objectives: Xingnao Kaiqiao (XNKQ) acupuncture is used clinically in prolonged disorders of consciousness (pDOC), but the cortical processes underlying its acute effects remain incompletely characterised. We used bedside functional near-infrared spectroscopy (fNIRS) with a superficial non-acupoint sham comparator to examine acute prefrontal hemodynamic responses in pDOC patients and healthy controls. Methods: Forty-five pDOC patients (25 minimally conscious state; 20 unresponsive wakefulness syndrome) and 127 healthy volunteers were enrolled; 124 healthy volunteers were retained for complete-case analysis. Participants received real XNKQ acupuncture or superficial sham needling at adjacent non-acupoints. fNIRS recorded oxyhaemoglobin (HbO) across three 8-min windows: pre-acupuncture (Before), steady-state needle retention (During), and post-acupuncture (After). Regional HbO was the principal analysis; connectivity-derived network, temporal, and baseline-association analyses were exploratory. Results: In healthy participants, real acupuncture produced greater HbO responses than sham across all four regions and the global prefrontal average (Cohen’s d = 0.62–1.20; all q ≤ 0.0011). In pDOC patients, the response was smaller and regionally restricted: the dorsolateral prefrontal cortex (DLPFC; d = 0.80, q = 0.0397) and global HbO ( d = 0.98, q = 0.0191) remained significant after false discovery rate (FDR) correction, whereas the frontopolar area (PFA) was borderline ( q = 0.0576), and the sensorimotor cortex and inferior frontal area (IFA) were not significant. Baseline-adjusted analyses showed the same general pattern. No connectivity-derived network contrast survived FDR correction. Baseline-to-change correlations were negative but mathematically coupled. Conclusion: Real XNKQ acupuncture was associated with greater acute prefrontal HbO responses than superficial non-acupoint needling. The effect was broad in healthy participants and more restricted in pDOC patients. These findings demonstrate an acute hemodynamic response, not clinical efficacy, preserved awareness, or strict acupoint specificity. Network and baseline association findings remain exploratory. Patient protocol registration: Chinese Clinical Trial Registry, https://www.chictr.org.cn , identifier ChiCTR2400090915 (registered 15 October 2024).

Vagus nerve stimulation (VNS), as a neuromodulation therapy, has shown promising prospects in the treatment of myocardial ischemia-reperfusion injury (MIRI) following myocardial infarction (MI). MIRI can exacerbate secondary damage to post-ischemic myocardial tissue. VNS can alleviate MIRI by enhancing vagal nerve activity. In preclinical studies, VNS exerts cardioprotective effects through multi-target synergistic regulation: inhibiting inflammatory cascades through the cholinergic anti-inflammatory pathway (CAP) and vagus nerve-spleen pathway, improving mitochondrial function, resisting oxidative stress, suppressing cardiomyocyte apoptosis, and regulating autonomic nerves to reduce arrhythmias risk. This review explores the interactions between the aforementioned mechanisms, rarely addressed in prior studies. Furthermore, this review summarizes relevant clinical studies, where VNS significantly reduces myocardial injury markers and arrhythmia incidence. However, VNS still faces clinical application challenges including unstandardized parameter and operation standards and insufficient clinical evidence. This review aims to bridge preclinical and clinical research, providing a reference for VNS clinical application in MIRI.