Mesenchymal stromal cells (MSCs) can modulate inflammation and contribute to tissue regeneration and, thus, have emerged as a promising option for cell-based therapy. However, the ability of MSCs to migrate to injured tissues still needs to be improved. In this study, we investigated whether genetically engineered MSCs could exhibit increased migratory properties and improved therapeutic efficacy. Using a mouse model of contact hypersensitivity (CHS), chemokine gene expression screening revealed that CXCL13 changed most significantly in injured tissue. Unfortunately, MSCs hardly express the corresponding receptor, CXCR5. Thus, CXCR5-overexpressing MSCs (MSC) were generated that retained their abilities of proliferation, differentiation, and immunomodulation. Furthermore, MSC showed significantly increased migrating ability toward CXCL13. Importantly, systemic infusion of MSC dramatically suppressed CHS in mice, as evidenced by decreased levels of inflammatory cell infiltration and pro-inflammatory cytokine production. Numerous MSC migrated into inflamed ears, localized with T cells, inhibited T cell proliferation, promoted T cell apoptosis, and suppressed the production of T cell-derived pro-inflammatory factors. Collectively, these findings demonstrate that CXCR5 overexpression increases the ability of MSCs to respond to migratory stimuli and highly intensifies their immunomodulatory effects in vivo. This strategy for enhancing targeted stem/progenitor cell homing may improve the efficacy of MSC-based therapies.

Mesenchymal stromal cells (MSCs) have shown significant heterogeneity in terms of therapeutic efficacy for inflammatory bowel disease (IBD) treatment, which may be due to an insufficient number of MSCs homing to the damaged tissue of the colon. Engineering MSCs with specific chemokine receptors can enhance the homing ability by lentiviral transduction. However, the unclear specific chemokine profile related to IBD and the safety concerns of viral-based gene delivery limit its application. Thus, a new strategy to modify MSCs to express specific chemokine receptors using mRNA engineering is developed to evaluate the homing ability of MSCs and its therapeutic effects for IBD. We found that CXCL2 and CXCL5 were highly expressed in the inflammatory colon, while MSCs minimally expressed the corresponding receptor CXCR2. Transient expression of CXCR2 in MSC was constructed and exhibited significantly enhanced migration to the inflamed colons, leading to a robust anti-inflammatory effect and high efficacy. Furthermore, the high expression of semaphorins7A on MSCs were found to induce the macrophages to produce IL-10, which may play a critical therapeutic role. This study demonstrated that the specific chemokine receptor CXCR2 mRNA-engineered MSCs not only improves the therapeutic efficacy of IBD but also provides an efficient and safe MSC modification strategy.

The aim of the present study was to quantitatively diagnose and monitor the therapy response of hepatic ischemia-reperfusion injury (IRI) with the use of targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated, and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs was observed. To establish a quantitative method based on targeted US imaging, contrast-enhanced US was applied for IRI rats. After andrographolide treatment, the IRI rats were subjected to the quantitative targeted US imaging for a therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed. According to the quantitative targeted US imaging, the ICAM-1 normalized intensity difference (NID) in the IRI rats (38.74 ± 15.08%) was significantly higher than that in the control rats (10.08 ± 2.52%, p = 0.048). Further, different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by the use of the NID (37.14 ± 2.14%, 22.34 ± 1.08%, p = 0.002). Analysis of mRNA expression demonstrated the accuracy of analyzing the NID by using quantitative targeted US imaging (R = 0.7434, p < 0.001). Andrographolide treatment resulted in an obviously weakened NID of ICAM-1 (17.7 ± 4.8% vs 34.2 ± 6.6%, p < 0.001). The study showed the potential of the quantitative targeted US imaging method for the diagnosis and therapeutic monitoring of IRI.

Background: Radiofrequency ablation (RFA) has been recommended as the treatment for benign thyroid nodules (BTNs) by some guidelines. However, detailed follow-up instructions for thyroid function about the timing and affected populations after RFA are lacked due to insufficient researches. This 12month prospective study aimed to evaluate the incidence and risk factors of thyroid dysfunction at different time points after RFA, especially within 1 week that previous studies didn't concern. Methods: Seventy-five euthyroid patients who underwent RFA for symptomatic BTNs were enrolled (ChiCTR-INR-16007884). The incidence of thyroid dysfunction within 1 week, at 1, 6, and 12 months after RFA was evaluated. The risk factors for different types of thyroid dysfunction in the different terms were further analyzed. Results: Within 1 week after RFA, the incidence of thyroid dysfunction was as high as 36.00% unexpectedly, and only overt thyrotoxicosis and subclinical thyrotoxicosis occurred, which were significantly associated with the low-normal baseline thyrotropin (TSH) level (p ¼ 0.001) and high ablation volume ratio (p ¼ 0.008). From 1 to 12 months (the long term), the incidence dropped significantly and remained low (8.00-12.00%); and thyroid dysfunction presented as overt thyrotoxicosis, subclinical thyrotoxicosis, and subclinical hypothyroidism. The long-term thyrotoxicosis group had more cases with diabetes and lower baseline TSH levels. The long-term subclinical hypothyroidism group had more cases with positive thyroid peroxidase antibodies, higher baseline TSH levels, and higher ablation volume ratios. Conclusions: After the RFA of BTNs, thyroid dysfunction was more likely to occur within 1 week and in populations with risk factors.

<b><i>Introduction:</i></b> Small-volume hydrodissection liquid dissipates rapidly and confers only short-term protection during radiofrequency ablation (RFA) of benign thyroid nodules. The aim of this study was to establish a safe method for continuous, large-volume hydrodissection. <b><i>Methods:</i></b> A long needle was inserted and positioned outside the thyroid capsule; 5% glucose was injected to maintain a 3- to 5-mm continuous safety buffer. From October 2015 to July 2020, 166 patients underwent hydrodissection with different volumes, and ablation efficacy and complications associated with different liquid volumes (≤40 mL vs. &#x3e;40 mL) were compared at 1-month postprocedure. Moreover, 20 mL liquid (equivalent to 250 mL in the human body) was injected around the thyroid of a rhesus monkey, after which CT scans were used to visualize the liquid’s fate and verify its safety. <b><i>Results:</i></b> The 51 patients with 10–40 mL injections and 116 patients with larger injections (45–450 mL) showed similar complete ablation rates (88.46% vs. 90.44%, <i>p</i> = 0.582), comparable 6-month VRR (82.79% vs. 76.62%, <i>p</i> = 0.079), and complication incidences, although the latter group had larger nodules (9.11 mL vs. 13.79 mL, <i>p</i> = 0.003), more energy delivered (3.44 kcal vs. 6.04 kcal, <i>p</i> &#x3c; 0.001), and longer operation times (51.37 min vs. 69.2 min, <i>p</i> &#x3c; 0.001). In the animal experiment, the 20 mL of liquid diffused quickly (within 10 min) from the vicinity of the thyroid to the mediastinum and retropharyngeal space. It was observed in the kidneys at 10 min and disappeared from the neck and chest space by 24 h. <b><i>Conclusions:</i></b> Continuous, large-volume hydrodissection can protect the delicate structures around the thyroid throughout the RFA procedure and might be beneficial in large thyroid nodule ablation.