Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA.

The cutoff amplitude of transcranial motor evoked potentials for transient postoperative motor deficits in intramedullary spinal cord tumor surgery.

STUDY DESIGN: Retrospective clinical study of intraoperative transcranial motor evoked potential (TcMEP) amplitudes and postoperative motor deficits (PMDs). OBJECTIVE: To determine the quantifiable cutoff amplitude of TcMEP for predicting transient PMDs in intramedullary spinal cord tumor (IMSCT) surgery. SUMMARY OF BACKGROUND DATA: The "presence or absence" criterion is reliable and widely used the alarm criterion for preventing permanent PMDs in IMSCT surgery. However, we wanted to prevent PMDs even if it is transient. The cutoff amplitude for transient PMDs should be identified. METHODS: We conducted a retrospective study to identify the cutoff amplitude for predicting transient PMDs in IMSCT surgery. Thirty-seven patients were included in the study. We examined intraoperative electrophysiological changes and perioperative motor status in these patients. Receiver operating characteristic analyses were performed to identify the cutoff amplitudes for predicting transient PMDs in IMSCT surgery. The incidence of PMDs and cutoff TcMEP amplitude in cervical and thoracic lesions were compared. RESULTS: Thirteen cases demonstrated transient PMDs. Among 280 monitorable muscles in 37 cases, 51 muscles in 13 patients showed PMDs. Through receiver operating characteristic analysis, the relative and the absolute cutoff amplitudes at the intraoperative point of deterioration were identified to be 12% residual of baseline amplitude and 3.2 µV, respectively. Sensitivity/specificity for those cutoff points are 86%/74% and 88%/78%, respectively. The incidence of PMD was significantly higher, and the cutoff amplitude was lower in the thoracic lesions than in the cervical lesions. CONCLUSION: We determined the cutoff TcMEP amplitude for predicting transient PMDs in IMSCT surgery. The cutoff amplitude for the cervical lesions was higher than that for the thoracic lesions. The results suggest the need for setting different alarm criteria in different level of spine. LEVEL OF EVIDENCE: 3.

The cutoff amplitude of transcranial motor-evoked potentials for predicting postoperative motor deficits in thoracic spine surgery.

STUDY DESIGN: Prospective clinical study of intraoperative transcranial motor-evoked potentials (TcMEP) amplitudes and postoperative motor deficits. OBJECTIVE: To determine the cutoff amplitude during intraoperative TcMEP monitoring for predicting postoperative motor deficits after thoracic spine surgery. SUMMARY OF BACKGROUND DATA: Several alarm points when monitoring with TcMEP have been advocated, but there have been no reports on an actual cutoff amplitude of TcMEP for predicting the occurrence of postoperative motor deficits. METHODS: Among 80 consecutive surgical cases, 28 had a deterioration in TcMEP amplitude in at least 1 monitored muscle during surgery. We examined intraoperative electrophysiological changes and postoperative motor deficits in 270 monitorable muscles in those 28 patients. Through receiver operating characteristic curve analysis, we identified the cutoff amplitudes at the intraoperative point of deterioration and at the end of surgery for predicting postoperative motor deficits in both relative and absolute values. RESULTS: The relative and the absolute cutoff amplitudes of TcMEP at the intraoperative point of deterioration and at the end of thoracic spine surgery were 12% of control amplitude and 1.9 µV and 25% of control amplitude and 3.6 µV, respectively. Sensitivity/specificity for those cutoff points are 88%/64%, 69%/83%, 90%/64%, and 70%/82%, respectively. CONCLUSION: We determined the cutoff amplitude for predicting postoperative motor deficits in thoracic spine surgery. The results may help establish the alarm criteria for thoracic spine surgery.