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Introduction: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods: Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results: Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration: ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901. [ABSTRACT FROM AUTHOR]

Highlights • In this manuscript we used a combination of lineage tracing techniques, conditional knockout and pharmacological inhibitor methods to study the mechanisms of MSCs in paraquat-induced pulmonary fibrosis. • Nestin + MSCs are source of fibrosis in paraquat-induced lung injury. • Blocking the chemotactic effects of MSCs by perivascular CXCL12 inhibition protects pulmonary injury following paraquat exposure. Abstract Background Paraquat (PQ) poisoning is one of the leading causes of suicide attempts in China signature by acute onset of respiratory distress with massive matrix production resulting in progressive pulmonary fibrosis. There is no specific antidote and mortality remains high without effective treatment available. The cellular mechanisms underlying PQ-induced pulmonary fibrosis remain largely unknown. Objectives To determine the origin of mesenchymal stem cells (MSCs) migrated to the lung after PQ exposure and their roles in PQ-induced pulmonary fibrosis, to further explore the possible mechanisms involved in these processes, and to help finding novel therapies. Methods We used a combination of lineage tracking techniques to investigate the contributions of several cells of MSCs, marked by Nestin or CXCL12, and traced their co-expression of α-smooth muscle actin (α-SMA), a marker for fibrosis, or their co-location with matrix production, marked by collagen-1 production (Col1-GFP) following PQ exposure. Then, we used a CXCL12flox/flox; Prx1-Cre mice and a pharmacologic agent AMD3100 to selectively deplete chemotactic mechanism of the MSCs, and tested pro-fibrotic pathways, fibrotic processes and survival of mice after PQ exposure. Results Our results showed that after paraquat exposure, the residential Nestin + MSCs were quickly expanded and contributed to extracellular matrix production. Moreover, when we used a CXCL12flox/flox; Prx1-Cre mice to selectively deplete chemotactic mechanism of the MSC, we found that PQ exposure in these mice failed to activate pro-fibrotic pathways including TGF-β, Wnt and EGFR signaling. Furthermore, when the chemotactic effect of MSCs via CXCL12 was blocked by a pharmacologic agent, AMD3100, it alleviated the development of the fibrotic process and improved survival rate in mice exposed to PQ. Conclusion Collectively, our data suggest paraquat intoxication rapidly activated Nestin + MSCs and that blocking chemotactic effects of MSCs by perivascular CXCL12 inhibition may effectively protect pulmonary injury following paraquat exposure. Our results revealed a novel mechanism for post-PQ lung injury and indicated a novel therapeutic option to attenuate fibrosis induced by paraquat. [ABSTRACT FROM AUTHOR]

The serious consequences of the global coronavirus disease 2019 (COVID-19) pandemic have prompted a rapid global response to develop effective therapies that can lessen disease severity in infected patients. Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health ClinicalTrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. Several recent published reports have suggested potential efficacy; however, the available data presented are either anecdotal or from incomplete, poorly controlled investigations. Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. The authors urge that the field proceed by finding a balance between swift experimentation and communication of results and scientifically coherent generation and analysis of clinical data., (38; Gene Therapy.)