A Preview of Selected Articles

Abstract

body components. Loss of or damage to cartilage can lead to the onset of conditions such as osteoarthritis, where the continual thinning of articular (a subset of hyaline) cartilage produces unwanted bone-on-bone contact within the joint, leading to pain and reduced motion. While we lack the endogenous healing capacity to fully recover from cartilage damage, the efficacy of current medicinal and surgical approaches also remains low [1]. Furthermore, we also lack a relevant supply of donor cartilage-producing chondrocytes for advanced tissue engineering approaches. However, studies have demonstrated that human bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into a spectrum of skeletal tissues, including cartilage [2], suggesting that transplantation of BM-MSCs into affected areas may promote cartilage defect repair given appropriate support. However, no protocols currently exist for the efficient in vivo generation of functional hyaline cartilage by BM-MSCs [3]. As an alternative approach, the secretion of protective, immunomodulatory, and regenerative factors by MSCs following transplantation has the potential to enhance previously unviable surgical approaches, such as the transplantation of allogeneic chondrocytes for cartilage defect repair. In our first Featured Article from Stem Cells Translational Medicine this month, Kuznetsov et al. provide the first in vivo demonstration of stable cartilage formation by human BM-MSCs, thanks to the support of fibrin microbeads coated with hyaluronic acid acting as a scaffold [4]. In a Related Article from Stem Cells, de Windt et al. report on a successful phase I trial that tested the one-stage application of allogeneic MSCs mixed with recycled defect-derived autologous chondrons for the treatment of cartilage defects [5]. Neutrophils are a type of phagocyte typically found in the bloodstream and are a vital component of the defense system against infection in humans. In patients undergoing stem cell transplantation or intensive chemotherapy, low levels of neutrophils (neutropenia) represent a significant risk for life-threatening bacterial and fungal infections. As treatment with broad-spectrum antibiotics and colony-stimulating factors still suffer from a 20% mortality rate in neutropenic patients, animal trials have begun to test neutrophil transfusions as a means to resolve infections, with some very encouraging results already reported [6, 7]. However, neutrophil transfusions used to treat infection in human neutropenic patients will require massive numbers of cells per kilogram body weight according to studies in infants [8] and another prospective randomized study [9]. Can the differentiation of neutrophils from induced pluripotent stem cells (iPSCs) provide the substantial number of neutrophils required for transfusions? In our second Featured Article from Stem Cells Translational Medicine this month, Trump et al. provide proof-of-concept for the efficient differentiation of human iPSCs into neutrophils that phagocytose bacteria in vitro and in vivo [10]. In a Related Article from Stem Cells, de Witte et al. tracked MSCs following intravenous infusion, discovering that monocytes, another phagocytic cell type with crucial roles in the immune system, engulf MSCs in the lungs and then migrate to other body sites to mediate, distribute, and transfer the immunomodulatory effect of MSCs [11].