Macrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were to evaluate the effect of bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos) on the phagocytic capability of macrophages to clear myelin debris and to investigate the underlying molecular mechanism during the spinal cord injury (SCI) process. This work reveals that monocyte-derived macrophages (MDMs) infiltrating into the SCI site could efficiently engulf myelin debris and process phagocytic material. However, the phagocytic ability of macrophages to clear tissue debris is compromised after SCI. The administration of BMSC-Exos as an approach for SCI treatment could rescue macrophage normal function by improving the phagocytic capability of myelin debris internalization, which is beneficial for SCI repair, as evidenced by better axon regrowth and increased hindlimb locomotor functional recovery in a rodent model. Examination of macrophage treatment with BMSC-Exos revealed that BMSC-Exos could promote the capacity of macrophages to phagocytose myelin debris in vitro and could create a regenerative microenvironment for axon regrowth. In addition, we confirmed that BMSC-Exo treatment resulted in improved phagocytosis of engulfed myelin debris by promoting the expression of macrophage receptor with collagenous structure (MARCO) in macrophages. The inhibition of MARCO with PolyG (a MARCO antagonist) impaired the effect of BMSC-Exos on the phagocytic capacity of macrophages and resulted in compromised myelin clearance at the lesion site, leading to further tissue damage and impaired functional healing after SCI. In conclusion, these data indicated that targeting the phagocytic ability of macrophages may have therapeutic potential for the improvement in functional healing after SCI. The administration of BMSC-Exos as a cell-free immune therapy strategy has wide application prospects for SCI treatment.
High mobility group N (HMGNs) are members of the high mobility group protein family, and are involved in the development and progression of several tumors. HMGN1 and HMGN5 were previously shown to be associated with the bioactivities of osteosarcoma. However, the effects and molecular mechanisms of HMGN2 on osteosarcoma progression remain to be determined. In order to characterize the endogenous expression of HMGN2 in osteosarcoma cell lines, RT-PCR and western blot analysis were performed. Recombinant HMGN2 lentivirus was used to infect the osteosarcoma cell lines with relatively low HMGN2 expression to determine the functional relevance of HMGN2 overexpression in osteosarcoma cell growth and migration in vitro and in vivo, and to investigate the expression levels of Ki-67, PCNA, cyclin D1 and cyclin E. The results showed that osteosarcoma cell proliferation and migration were significantly reduced by HMGN2, as indicated by cell count and wound-healing assays. Cell apoptosis was markedly induced and HMGN2 increased the sensitivity to chemotherapy. When HMGN2 expression was enhanced, the expression of cyclin D1 and PCNA was downregulated in osteosarcoma cells. In addition, the tumor volumes in SaO2 and U2-OS subcutaneous nude mouse models treated with HMGN2 lentivirus were significantly decreased as compared to those of the GFP group. These results suggested that the enhanced expression of HMGN2 in osteosarcoma cells by HMGN2 lentivirus, exerts inhibitory effects on growth and migration of osteosarcoma cells.
Study design
This is a retrospective study.
Background
To assess and compare the clinical outcomes of posterior unilateral limited laminectomy (ULL) or bilateral laminectomy (BL) debridement and bone grafting fusion combined with internal fixation among aged patients with single-segment thoracic and lumbar tuberculosis (SST/LTB).
Materials and methods
We performed a retrospective study on aged patients (age > 65 years old) with SST/LTB from January 2010 to October 2018. We reviewed 36 aged patients who were treated with BL and 31 aged patients treated with ULL. All participants had undergone and finished a three-year follow-up. The outcomes were evaluated by the improvement of neurological function, correction Cobb angle, bone fusion time, and back pain, as well as operative time, blood loss, hospital stay, and postoperative complications.
Results
The operative time, blood loss volume, and incidence of complications in group B were significantly less than those in group A (P < 0.01). The postoperative kyphotic angle in both groups was reduced significantly compared to the preoperative status (P < 0.01). The percentage of neurological improvement was 92.9% in group A and 90.9% in group B. All patients achieved solid bone fusion after surgery. At three-year follow-up, the angle loss in group B was significantly less than that in group A (P < 0.01); Furthermore, patients in group B had a lower average visual analog scale score of back pain and Oswestry Disability Index score than patients in group A (P < 0.05).
Conclusions
For aged patients with SST/LTB, ULL is a safer and more effective surgical treatment than BL.
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