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Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential: winner of the Society for Biomaterials Student Award in the Undergraduate Category, Charlotte, NC, April 15 to 18, 2015.

ABSTRACT: Cell-cell contact-mediated Notch signaling is essential for mesenchymal stem cell (MSC) chondrogenesis during development. However, subsequent deactivation of Notch signaling is also required to allow for stem cell chondrogenic progression. Recent literature has shown that Notch signaling can also influence Wnt/?-catenin signaling, critical for MSC differentiation, through perturbations in cell-cell contacts. Traditionally, abundant cell-cell contacts, consistent with development, are emulated in vitro using pellet cultures for chondrogenesis. However, cells are often encapsulated within biomaterials-based scaffolds, such as hydrogels, to improve therapeutic cell localization in vivo. To explore the role of Notch and Wnt/?-catenin signaling in the context of hydrogel-encapsulated MSC chondrogenesis, we compared signaling and differentiation capacity of MSCs in both hydrogels and traditional pellet cultures. We demonstrate that encapsulation within poly(ethylene glycol) hydrogels reduces cell-cell contacts, and both Notch (7.5-fold) and Wnt/?-catenin (84.7-fold) pathway activation. Finally, we demonstrate that following establishment of cell-cell contacts and transient Notch signaling in pellet cultures, followed by Notch signaling deactivation, resulted in a 1.5-fold increase in MSC chondrogenesis. Taken together, these findings support that cellular condensation, and establishment of initial cell-cell contacts is critical for MSC chondrogenesis, and this process is inhibited by hydrogel encapsulation.

SUBMITTER: Chen AX

PROVIDER: S-EPMC4344387 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential: winner of the Society for Biomaterials Student Award in the Undergraduate Category, Charlotte, NC, April 15 to 18, 2015.

Chen Amanda X AX Hoffman Michael D MD Chen Caressa S CS Shubin Andrew D AD Reynolds Daniel S DS Benoit Danielle S W DS

Journal of biomedical materials research. Part A 20141231 4

Cell-cell contact-mediated Notch signaling is essential for mesenchymal stem cell (MSC) chondrogenesis during development. However, subsequent deactivation of Notch signaling is also required to allow for stem cell chondrogenic progression. Recent literature has shown that Notch signaling can also influence Wnt/β-catenin signaling, critical for MSC differentiation, through perturbations in cell-cell contacts. Traditionally, abundant cell-cell contacts, consistent with development, are emulated i ...[more]

PMID: 25504509

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Project description:Background/Objective People with spinal cord injury (SCI) access educational resources during their inpatient rehabilitation, but they can be overwhelmed by the amount of information they need to assimilate during ever-shorter stays. This project created e-learning courses to fill the knowledge needs of SCI consumers and evaluated user satisfaction and knowledge transfer. Methods/Overview A needs assessment of 83 consumers and 99 staff identified information needs for people with SCI (Toronto Rehabilitation Institute – UHN and CPAO, 2008). Key topics were selected for the creation of 10 online patient education courses, collectively called Spinal Cord Injury – University (SCI-U), and housed on the Spinal Cord Connections website (www.spinalcordconnections.ca/sci-u). Course content was developed collaboratively by over 100 consumers and professionals, from healthcare and community service organizations across Canada. Each course uses adult learning principles and presents key information on healthy living with SCI, in an accessible and engaging way. A team of professionals created multimedia courses using Articulate software, incorporating video, animation and interactivity. The courses show the positive faces of SCI, each one featuring 3 video presenters (all people with SCI), and video testimonials where consumers talk about their experience living with SCI and managing their health. Users are encouraged to complete course quizzes to reinforce their learning. A pilot study enrolled consumers and clinicians (n = 25) and evaluated knowledge acquisition and retention, as well as perceived utility and satisfaction with the first 3 courses in the series: SCI and You, Bladder and Bowel. Results Knowledge acquisition and retention: across-group mean pre-course, post-course and 1-month post-course scores were “SCI & You” (score/14) 8.19, 10.67, 10.75; “Bladder” (score/13) 5.73, 8.69, 7.09; and “Bowel” (score/12) 6.68, 9.23, 9.00. Perceived utility and satisfaction: across-group mean global satisfaction scores (/5) were “SCI & You” 4.25, “Bladder” 3.89, and “Bowel” 3.94. Across-group mean global effectiveness scores (/5) were “SCI & You”? 4.16, “Bladder” 4.36, and “Bowel” 4.28. Visits to the SCI-U home page were 773 (2010), 2084 (2011) and 803 (as of March 2012). Conclusions SCI-U is an effective tool for patient education, and integrating e-learning into SCI rehabilitation programs has the potential to improve the effectiveness of knowledge transfer. Acknowledgements Rick Hansen Institute Grant Number: 2010-77.

Project description:Over the last years, evidence has accumulated in support of bracing as an effective treatment option in patients with idiopathic scoliosis. Yet, little information is available on the impact of compliance on the outcome of conservative treatment in scoliotic subjects. The aim of the present study was to prospectively evaluate the association between compliance to brace treatment and the progression of scoliotic curve in patients with idiopathic adolescent (AIS) or juvenile scoliosis (JIS).Among 1.424 patients treated for idiopathic scoliosis, 645 were eligible for inclusion criteria. Three outcomes were distinguished in agreement with the SRS criteria: curve correction, curve stabilization and curve progression. Brace wearing was assessed by one orthopaedic surgeon (LA) and scored on a standardized form. Compliance to treatment was categorized as complete (brace worn as prescribed), incomplete A (brace removed for 1 month), incomplete B (brace removed for 2 months), incomplete C (brace removed during school hours), and incomplete D (brace worn overnight only). Chi square test, T test or ANOVA and ANOVA for repeated measures tests were used as statistical tests.The results from our study showed that at follow-up the compliance was: Complete 61.1%; Incomplete A 5.2%; Incomplete B 10.7%; Incomplete C 14.2%; Incomplete D 8.8%. Curve correction was accomplished in 301/319 of Complete, 19/27 Incomplete A, 25/56 Incomplete B, 52/74 Incomplete C, 27/46 Incomplete D. Cobb mean value was 29.8?±?7.5 SD at beginning and 17.1?±?10.9 SD at follow-up. Both Cobb and Perdriolle degree amelioration was significantly higher in patients with complete compliance over all other groups, both in juvenile, both in adolescent scoliosis. In the intention-to-treat analysis, the rate of surgical treatment was 2.1% among patients with definite outcome and 12.1% among those with drop-out. Treatment compliance showed significant interactions with time.Curve progression and referral to surgery are lower in patients with high brace compliance. Bracing discontinuation up to 1 month does not impact on the treatment outcome. Conversely, wearing the brace only overnight is associated with a high rate of curve progression.

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Dataset Information

Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential: winner of the Society for Biomaterials Student Award in the Undergraduate Category, Charlotte, NC, April 15 to 18, 2015.

Publications

Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential: winner of the Society for Biomaterials Student Award in the Undergraduate Category, Charlotte, NC, April 15 to 18, 2015.

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