SummarySchwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system.
Although skin cell‐printing has exhibited promises for fabrication of functional skin equivalents, existing skin models through 3D cell printing are still composed of dermal and epidermal layers. However, a key hope for printing skin is to improve structural complexity of human skin over conventional construction, enabling the precise localization of multiple cell types and biomaterials. Here, the complexity of skin anatomy is increased using 3D cell printing. A novel printing platform is suggested for engineering a matured perfusable vascularized 3D human skin equivalent composed of epidermis, dermis, and hypodermis. The skin model is evaluated using functional markers representing each region of epidermis, dermis, and hypodermis to confirm tissue maturation. It is hypothesized that the vascularized dermal and hypodermal compartments that provide a more realistic microenvironment can promote cross‐talks with the epidermal compartment, producing better recapitulation of epidermal morphogenesis. Skin stemness in epithelial tissue is investigated. These findings reveal that the full‐thickness skin has more similarities to the native human skin compared with the dermal and epidermal skin model, indicating that it better reflects the actual complexity of native human skin. It is envisioned that it offers better predictive and reliable in vitro platform for investigation of mechanisms of pathological research and skin disease modeling.
To overcome the drawbacks of in vitro liver testing during drug development, numerous liver-on-a-chip models have been developed. However, current liver-on-a-chip technologies are labor-intensive, lack extracellular matrix (ECM) essential for liver cells, and lack a biliary system essential for excreting bile acids, which contribute to intestinal digestion but are known to be toxic to hepatocytes. Therefore, fabrication methods for development of liver-on-a-chip models that overcome the above limitations are required. Cell-printing technology enables construction of complex 3D structures with multiple cell types and biomaterials. We used cell-printing to develop a 3D liver-on-a-chip with multiple cell types for co-culture of liver cells, liver decellularized ECM bioink for a 3D microenvironment, and vascular/biliary fluidic channels for creating vascular and biliary systems. A chip with a biliary fluidic channel induced better biliary system creation and liver-specific gene expression and functions compared to a chip without a biliary system. Further, the 3D liver-on-a-chip showed better functionalities than 2D or 3D cultures. The chip was evaluated using acetaminophen and it showed an effective drug response. In summary, our results demonstrate that the 3D liver-on-a-chip we developed is promising in vitro liver test platform for drug discovery.
We used 3D cell printing to emulate an airway coupled with a naturally-derived blood vessel network in vitro. Decellularized extracellular matrix bioink derived from porcine tracheal mucosa (tmdECM) was used to encapsulate and print endothelial cells and fibroblasts within a designated polycarprolactone (PCL) frame. Providing a niche that emulates conditions in vivo, tmdECM gradually drives endothelial re-orientation, which leads to the formation of a lumen and blood vessel network. A fullydifferentiated in vitro airway model was assembled with the printed vascular platform, and collectively reproduced a functional interface between the airway epithelium and the vascular network. The model presented respiratory symptoms including asthmatic airway inflammation and allergen-induced asthma exacerbation in physiological context. Because of the adaptable and automated nature of direct 3D cell printing, we expect that this will have relevance in vivo and high reproducibility for production of high-content platforms for preclinical trials in biomedical research.
Although women’s underrepresentation in senior-level positions in the workplace has multiple causes, women’s self-improvement or “empowerment” at work has recently attracted cultural attention as a solution. For example, the bestselling book Lean In states that women can tackle gender inequality themselves by overcoming the “internal barriers” (e.g., lack of confidence and ambition) that prevent success. We sought to explore the consequences of this type of women’s empowerment ideology. Study 1 found that perceptions of women’s ability to solve inequality were associated with attributions of women’s responsibility to do so. Studies 2, 3, 5a, and 5b experimentally manipulated exposure to women’s empowerment messages, finding that while such messages increase perceptions that women are empowered to solve workplace gender inequality, they also lead to attributions that women are more responsible both for creating and solving the problem. Study 4 found a similar pattern in the context of a specific workplace problem, and found that such messages also lead to a preference for interventions focused on changing women rather than changing the system. Studies 5a and 5b sought to replicate prior studies and document the weakened effects of messages that explicitly explain that women’s “internal barriers” are the products of “external barriers” obstructing women’s progress. This research suggests that self-improvement messages intended to empower women to take charge of gender inequality may also yield potentially harmful societal beliefs.
The pursuit of passion in one’s work is touted in contemporary discourse. Although passion may indeed be beneficial in many ways, we suggest that the modern cultural emphasis may also serve to facilitate the legitimization of unfair and demeaning management practices—a phenomenon we term the legitimization of passion exploitation. Across 7 studies and a meta-analysis, we show that people do in fact deem poor worker treatment (e.g., asking employees to do demeaning tasks that are irrelevant to their job description, asking employees to work extra hours without pay) as more legitimate when workers are presumed to be “passionate” about their work. Of importance, we demonstrate 2 mediating mechanisms by which this process of legitimization occurs: (a) assumptions that passionate workers would have volunteered for this work if given the chance (Studies 1, 3, 5, 6, and 8), and (b) beliefs that, for passionate workers, work itself is its own reward (Studies 3, 4, 5, 6, and 8). We also find support for the reverse direction of the legitimization process, in which people attribute passion to an exploited (vs. nonexploited) worker (Study 7). Finally, and consistent with the notion that this process is connected to justice motives, a test of moderated mediation shows this is most pronounced for participants high in belief in a just world (Study 8). Taken together, these studies suggest that although passion may seem like a positive attribute to assume in others, it can also license poor and exploitative worker treatment.
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