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Introduction-Notch signaling is amongst the key intrinsic mechanisms regulating satellite cell fate, promoting the transition of activated satellite cells to highly proliferative myogenic progenitor cells and preventing their premature differentiation. Although much is known about the biochemical milieu that drives myogenic progression, less is known about the spatial cues providing spatiotemporal control of skeletal muscle repair in the context of Notch signaling. Methods-Using a murine injury model, we quantified in vivo biophysical changes that occur within the skeletal muscle during regeneration. Employing tunable poly(ethylene glycol)-based hydrogel substrates, we modeled the measured changes in bulk stiffness in the context of Notch ligand signaling, which are present in the regenerative milieu at the time of injury. Results-Following injury, there is a transient increase in the bulk stiffness of the tibialis anterior muscle that may be explained in part by changes in extracellular matrix deposi-tion. When presented to primary myoblasts, Jagged-1, Jagged-2, and Dll1 in a tethered format elicited greater degrees of Notch activity compared to their soluble form. Only tethered Jagged-1 effects were tuned by substrate stiffness, with the greatest Notch activation observed on stiff hydrogels matching the stiffness of regenerating muscle. When exposed to tethered Jagged-1 on stiff hydrogels, fewer primary myoblasts expressed myogenin, and pharmacological inhibitor studies suggest this effect is Notch and RhoA dependent. Conclusion-Our study proposes that tethered Jagged-1 presented in the context of transient tissue stiffening serves to tune Notch activity in myogenic progenitors during skeletal muscle repair and delay differentiation.

The human placental barrier facilitates many key functions during pregnancy, most notably the exchange of all substances between the mother and fetus. However, preclinical models of the placental barrier often lacked the multiple cell layers, syncytialization of the trophoblast cells and the low oxygen levels that are present within the body. Therefore, we aimed to design and develop an in vitro model of the placental barrier that would reinstate these factors and enable improved investigations of barrier function. BeWo placental trophoblastic cells and human umbilical vein endothelial cells were co-cultured on contralateral sides of an extracellular matrix-coated transwell insert to establish a multilayered barrier. Epidermal growth factor and forskolin led to significantly increased multi-nucleation of the BeWo cell layer and increased biochemical markers of syncytial fusion, for example syncytin-1 and hCGβ. Our in vitro placental barrier possessed size-specific permeability, with 4000-Da molecules experiencing greater transport and a lower apparent permeability coefficient than 70 000-Da molecules. We further demonstrated that the BeWo layer had greater resistance to smaller molecules compared to the endothelial layer. Chronic, physiologically low oxygen exposure (3–8%) increased the expression of hypoxia-inducible factor 1α and syncytin-1, further increased multi-nucleation of the BeWo cell layer and decreased barrier permeability only against smaller molecules (457 Da/4000 Da). In conclusion, we built a novel in vitro co-culture model of the placental barrier that possessed size-specific permeability and could function under physiologically low oxygen levels. Importantly, this will enable future researchers to better study the maternal–fetal transport of nutrients and drugs during pregnancy.

BACKGROUND Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non‐Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS The Stem Cell Club is a non‐profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (http://www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor‐database. Of the recruited registrants, 58.3% were male; 60.3% of males self‐reported as non‐Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor‐database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.

Background and Objectives: Communities of practice (CoPs) represent effective models to achieve quality outcomes in health care. We report the development and evaluation of a CoP to improve stem cell donor recruitment in Canada. Materials and Methods:In September 2017, we invited national stakeholders in stem cell donor recruitment to participate in a Facebook group and regular e-meetings. E-meetings involved speakers and roundtable discussion on topics related to donor recruitment. The Facebook group facilitated sharing of resources. We evaluated stakeholder perspective of the CoP and the impact on recruitment outcomes.Results: As of December 2020, the CoP included 382 members who published 243 posts to the Facebook group about patient/donor stories (40%), resources (27%), updates/questions (21%) and recruitment outcomes (12%). In January 2020, we surveyed 44 CoP participants; the majority felt that the Facebook group (86%) and e-meetings (59%) supported the community, and that the CoP fostered collaboration (82%), improved their donor recruitment knowledge (75%) and practice (77%) and improved their ability to recruit needed donors (64%). The launch of the CoP

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Background: Recruitment of committed unrelated hematopoietic stem cell donors from the most-needed demographics remains a challenge for donor recruitment organizations worldwide. Multimedia resources are gaining attention as a modality to support recruitment efforts; however, there is a lack of guidance for the development of such tools. This qualitative study explores the perspectives of eligible stem cell donors on an educational whiteboard video about stem cell donation, generating insights into how whiteboard videos and related multimedia may be optimized for donor recruitment. Study Design and Methods: Eight semistructured focus groups were conducted with 38 potential donors from the most-needed demographics (young, male, and non-Caucasian) after they had watched a 3.5-minute whiteboard video explaining key concepts in stem cell donation (https://youtu.be/ V4fVBtxnWfM). Constructivist grounded theory was used to identify themes and to develop a framework for understanding participants' preferred features of recruitment multimedia. Results: Participants identified a range of features contributing to the effectiveness of recruitment multimedia, adding that the whiteboard video is an effective, integrated, and readily accessible format for supporting donor recruitment. Topics that participants felt are important to address include knowledge gaps regarding donation procedures, concerns about donor safety, and the particular need for specific donor demographics. Suggested avenues for improvement include the addition of donor/recipient/patient personal experiences, attention-grabbing hooks, and a call to action including opportunities for further learning.