Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.

Bone is one of the most common sites of tumor metastases. During the last step of bone metastasis, cancer cells colonize and disrupt the bone matrix, which is maintained mainly by osteocytes, the most abundant cells in the bone microenvironment. However, the role of osteocytes in bone metastasis is still unclear. Here, we demonstrated that osteocytes transfer mitochondria to metastatic cancer cells and trigger the cGAS/STING-mediated antitumor response. Blocking the transfer of mitochondria by specifically knocking out mitochondrial Rho GTPase 1 (Rhot1) or mitochondrial mitofusin 2 (Mfn2) in osteocytes impaired tumor immunogenicity and consequently resulted in the progression of metastatic cancer toward the bone matrix. These findings reveal the protective role of osteocytes against cancer metastasis by transferring mitochondria to cancer cells and potentially offer a valuable therapeutic strategy for preventing bone metastasis.

Finite element analysis of sacral-alar-iliac screw fixation for sacroiliac joint dislocation.

The percutaneous sacroiliac (SI) screw is a common fixation option for posterior ring disruption in pelvic fractures. However, SI screw placement is difficult and can injure adjacent neurovascular structures. The sacral-alar-iliac screw (SAI) is a safe, reliable free-hand sacral pelvic fixation technique. To investigate the biomechanical stability of SAI for SI joint dislocation, finite element analysis was performed in unstable Tile-Type B and C pelvic ring injuries. The displacement in S1 (fixation of a unilateral S1 segment with one SI screw), TS1 (fixation of the S1 segment with a transsacra 1 screw), TS2 (fixation of the S2 segment with a transsacra 2 screw), S1AI, and S2AI exceeded the normal SI joint mobility. Sufficient stability after SI joint dislocation was obtained with (TS1 + TS2), (TS2 + S1), (S1AI + S2AI + rod), (S1AI + S2AI), and (S1 + S2AI + S1 pedicle) fixation. The TS1 + TS2 group had the smallest displacement and lowest peak screw stress, followed by (S1 + S2AI + S1 pedicle) placement. Our findings suggest that SAI screws are a valuable option for SI joint dislocation.

Surgical Options for Aggressive Vertebral Hemangiomas：A case series, literature review and treatment recommendations.

Purpose: We retrospectively study twenty-nine surgical cases of aggressive vertebral hemangiomas (AVHs) with neurological deficits and extradural compression to determine the optimal surgical treatment strategy for AVHs at a single institution. Methods: Patients with AVHs with neurological deficits who underwent partial tumor resection plus decompression with or without vertebroplasty (VP), and radiotherapy between 2010 and 2021 were included in this study. Clinical characteristics, surgical outcomes, and follow-up data of the patients were reviewed retrospectively. Results: Twenty-nine AVH cases with neurological deficits and spinal instability were included in this study and treated surgically. The mean operation time of patients with decompression surgery plus VP (Groupe A) was 215.9 (120-265 min), shorter than that of decompression surgery without VP (Group B) 240.2 (120-320 min). Intraoperative blood loss was 273.3 (100-550 mL) in group A and 635.3 (200-1600 mL) in group B. In addition, a significant reduction in blood loss was observed in group A compared to the group B (p=0.0001). All patients experienced immediate pain relief and improvement in their neurological symptoms. Neurological function was assessed by the Frankel score, ASIA score, and the visual analogue scale (VAS) pain score decreased from 7.4 (4-9) to 1.3 (0-3). Of twenty-nine patients in this study,  only 7% (2/29 patients) showed signs of recurrence. Conclusion: Decompression plus VP achieve good tumor control and decrease surgical complication. Preoperative vascular embolization and VP can reduce intraoperative bleeding in the treatment of AVH surgery. Moreover, postoperative radiotherapy seems to be a good technique to prevent tumor recurrence.

Rejuvenation of tendon stem/progenitor cells for functional tendon regeneration through platelet-derived exosomes loaded with recombinant Yap1.

The regenerative capabilities including self-renewal, migration and differentiation potentials shift from the embryonic phase to the mature period of endogenous tendon stem/progenitor cells (TSPCs) characterize restricted functions and disabilities following tendon injuries. Recent studies have shown that tendon regeneration and repair rely on multiple specific transcription factors to maintain TSPCs characteristics and functions. Here, we demonstrate Yap, a Hippo pathway downstream effector, is associated with TSPCs phenotype and regenerative potentials through gene expression analysis of tendon development and repair process. Exosomes have been proven an efficient transport platform for drug delivery. In this study, purified exosomes derived from donor platelets are loaded with recombinant Yap1 protein (PLT-Exo-Yap1) via electroporation to promote the stemness and differentiation potentials of TSPCs in vitro. Programmed TSPCs with Yap1 import maintain stemness and functions after long-term passage in vitro. The increased oxidative stress levels of TSPCs are related to the phenotype changes in duplicative senescent processes. The results show that treatment with PLT-Exo-Yap1 significantly protects TSPCs against oxidative stressor-induced stemness loss and senescence-associated secretory phenotype (SASP) through the NF-κB signaling pathway. In addition, we fabricate an Exos-Yap1-functioned GelMA hydrogel with a parallel-aligned substrate structure to enhance TSPCs adhesion, promote cell stemness and force regenerative cells toward the tendon lineage for in vitro and in vivo tendon regeneration. The application of Exos-Yap1 functioned implant assists new tendon-like tissue formation with good mechanical properties and locomotor functions in a full-cut Achilles tendon defect model. Thus, PLT-Exo-Yap1-functionalized GelMA promotes the rejuvenation of TSPCs to facilitate functional tendon regeneration. STATEMENT OF SIGNIFICANCE: This is the first study to explore that the hippo pathway downstream effector Yap is involved in tendon aging and repair processes, and is associated with the regenerative capabilities of TSPCs. In this syudy, Platelet-derived exosomes (PLT-Exos) act as an appropriate carrier platform for the delivery of recombinant Yap1 into TSPCs to regulate Yap activity. Effective Yap1 delivery inhibit oxidative stress-induced senescence associated phenotype of TSPCs by blocking ROS-mediated NF-κb signaling pathway activation. This study emphasizes that combined application of biomimetic scaffolds and Yap1 loaded PLT-Exos can provide structural support and promote rejuvenation of resident cells to assist functional regeneration for Achilles tendon defect, and has the prospect of clinical setting.

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+ T cells, which led to improved antitumor outcomes. Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation. Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.