Fibroblasts Close a Void in Free Space by a Purse-String Mechanism

The mechanism by which stromal cells fill voids in injured tissue remains a fundamental question in regenerative medicine. While it is well-established that fibroblasts fill voids by depositing extracellular matrix (ECM) proteins as they migrate toward the wound site, little is known about their ability to adopt an epithelial-like purse-string behavior. To investigate fibroblast behavior during gap closure, we created an artificial wound with a large void space. We discovered that fibroblasts could form a freestanding bridge over deep microvoids, closing the void via purse string contraction, a mechanism previously thought to be unique to epithelial wound closure. The findings also revealed that myosin II mediated contractility and intercellular adherent junctions were required for the closure of the fibroblast gap in our fabricated threedimensional artificial wound. To fulfill their repair function under the specific microenvironmental conditions of wounds, fibroblasts appeared to acquire the structural features of epithelial cells, namely, contractile actin bundles that span over multiple cells along the boundary. These findings shed light on a novel mechanism by which stromal cells bridge the 3D gap during physiological processes such as morphogenesis and wound healing.N

COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials

Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active malignancies, and thus data on the safety, tolerability and efficacy of the vaccines in patients with cancer are currently limited. Given the risk posed by the COVID-19 pandemic, decisions regarding the use of vaccines against COVID-19 in patients participating in trials of investigational anticancer therapies need to be addressed promptly. Patients should not have to choose between enrolling on oncology clinical trials and receiving a COVID-19 vaccine. Clinical trial sponsors, investigators and treating physicians need operational guidance on COVID-19 vaccination for patients with cancer who are currently enrolled or might seek to enrol in clinical trials. Considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. Herein, we provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials. In our perspective, continued quality oncological care requires that patients with cancer, including those involved in trials, be prioritized for COVID-19 vaccination, which should not affect trial eligibility