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Early Transplantation of Mesenchymal Stem Cells After Spinal Cord Injury Relieves Pain Hypersensitivity Through Suppression of Pain-Related Signaling Cascades and Reduced Inflammatory Cell Recruitment
Get PDFThis novel study demonstrated that mesenchymal stem cell transplants after spinal cord injury reduce neuropathic pain, giving details of reduced pain signalling pathways affected. The work is essential in the translation of stem cell therapies for CNS regeneration.Bone marrow-derived mesenchymal stem cells (BMSC) modulate inflammatory/immune responses and promote motor functional recovery after spinal cord injury (SCI). However, the effects of BMSC transplantation on central neuropathic pain and neuronal hyperexcitability after SCI remain elusive. This is of importance because BMSC-based therapies have been proposed for clinical treatment. We investigated the effects of BMSC transplantation on pain hypersensitivity in green fluorescent protein (GFP)-positive bone marrow-chimeric mice subjected to a contusion SCI, and the mechanisms of such effects. BMSC transplantation at day 3 post-SCI improved motor function and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. The pain improvements were mediated by suppression of protein kinase C-γ and phosphocyclic AMP response element binding protein expression in dorsal horn neurons. BMSC transplants significantly reduced levels of p-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (p-ERK1/2) in both hematogenous macrophages and resident microglia and significantly reduced the infiltration of CD11b and GFP double-positive hematogenous macrophages without decreasing the CD11b-positive and GFP-negative activated spinal-microglia population. BMSC transplants prevented hematogenous macrophages recruitment by restoration of the blood-spinal cord barrier (BSCB), which was associated with decreased levels of (a) inflammatory cytokines (tumor necrosis factor-α, interleukin-6); (b) mediators of early secondary vascular pathogenesis (matrix metallopeptidase 9); (c) macrophage recruiting factors (CCL2, CCL5, and CXCL10), but increased levels of a microglial stimulating factor (granulocyte-macrophage colony-stimulating factor). These findings support the use of BMSC transplants for SCI treatment. Furthermore, they suggest that BMSC reduce neuropathic pain through a variety of related mechanisms that include neuronal sparing and restoration of the disturbed BSCB, mediated through modulation of the activity of spinal-resident microglia and the activity and recruitment of hematogenous macrophages
Comparison of Mesenchymal Stromal Cells Isolated From Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury
Get PDFThe use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in
preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal
cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular
supply. Also, the transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this study was to compare
adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs) isolated from individual C57BL6/J mice in
relation to: (i) cellular characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free conditions, and (iii) cellular
survival rates after transplantation. AD-MSCs and BM-MSCs exhibited a similar cell surface marker profile, but expressed
different levels of growth factors and cytokines. To research their relative stress tolerance, both types of stromal cells were
incubated at 20.5% O2 or 1.0% O2 for 7 days. Results showed that AD-MSCs were more proliferative with greater culture
viability under these hypoxic conditions than BM-MSCs. The MSCs were also incubated under H2O2-induced oxidative stress
and in serum-free culture medium to induce stress. AD-MSCs were better able to tolerate these stress conditions than BMMSCs; similarly when transplanted into the spinal cord injury region in vivo, AD-MSCs demonstrated a higher survival rate
post transplantation Furthermore, this increased AD-MSC survival post transplantation was associated with preservation of
axons and enhanced vascularization, as delineated by increases in anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an attractive
alternative to BM-MSCs for the treatment of severe spinal cord injury. However, it should be noted that the motor function
was equally improved following moderate spinal cord injury in both groups, but with no significant improvement seen
unfortunately following severe spinal cord injury in either grou
An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically Relevant Cell Scaffolds Used for Cartilage Repair
No full textAim: To compare the incorporation, growth, and chondrogenic potential of bone marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds used for cartilage repair.
Methods: Human BM and AT MSCs were isolated, culture expanded, and characterised using standard protocols, then seeded into 2 different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion, incorporation, and viable cell growth were assessed microscopically and following calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were treated with chondrogenic inducers for 28 days. Extracellular matrix deposition and soluble glycosaminoglycan (GAG) release into the culture medium was measured at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay, respectively.
Results: A greater number of viable MSCs from either source adhered and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell scaffolds, this incorporation represented less than 2% of the cells that were seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro-Gide. MSCs from both sources underwent chondrogenic differentiation following induction. However, cartilaginous extracellular matrix deposition was most marked in Chondro-Gide seeded with BM MSCs. Soluble GAG secretion increased in chondrogenic versus control conditions. There was no marked difference in GAG secretion by MSCs from either cell source.
Conclusion: Chondro-Gide and Alpha Chondro Shield were permissive to the incorporation and chondrogenic differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs demonstrated the greatest increase in MSC number and deposition of a cartilaginous tissue
Influence of contextual factors, technical performance and movement demands on the subjective task load associated with professional rugby league match-play
Get PDFAccepted author manuscript version reprinted, by permission, from International Journal of Sports Physiology and Performance, 2021, 16(6), 763-771, https://doi.org/10.1123/ijspp.2019-0998. © Human Kinetics, Inc.Purpose: The aim of the study was to identify the association between several contextual match factors, technical performance and external movement demands on the subjective task load of elite rugby league players. Methods: Individual subjective task load, quantified using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), was collected from 29 professional rugby league players from one club competing in the European Super League throughout the 2017 season. The sample consisted of 26 matches, culminating in 441 individual data points. Linear mixed-modelling was adopted to analyze the data for relationships and revealed that various combinations of contextual factors, technical performance and movement demands were associated with subjective task load. Results: Greater number of tackles (effect size correlation ± 90% CI; η2= 0.18 ±0.11), errors (η2= 0.15 ±0.08) decelerations (η2= 0.12 ±0.08), increased sprint distance (η2= 0.13 ±0.08), losing matches (η2= 0.36 ±0.08) and increased perception of effort (η2= 0.27 ±0.08) led to most likely – very likely increases in subjective total task load. The independent variables included in the final model for subjective mental demand (match outcome, time played and number of accelerations) were unclear, excluding a likely small correlation with the number of technical errors (η2= 0.10 ±0.08). Conclusions: These data provide a greater understanding of the subjective task load and their association with several contextual factors, technical performance and external movement demands during rugby league competition. Practitioners could use this detailed quantification of internal loads to inform the prescription of recovery sessions and current training practices
New self-dual codes of length 68 from a 2 × 2 block matrix construction and group rings
Get PDFThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Advances in Mathematics of Communications following peer review. The definitive publisher-authenticated version Bortos, M., Gildea, J., Kaya, A., Korban, A. & Tylyshchak,A. (2020). New self-dual codes of length 68 from a 2 × 2 block matrix construction and group rings. Advances in Mathematics of Communications. is available online at: https://www.aimsciences.org/article/doi/10.3934/amc.2020111Many generator matrices for constructing extremal binary self-dual codes of different
lengths have the form G = (In | A); where In is the n x n identity matrix and A is
the n x n matrix fully determined by the first row. In this work, we define a generator
matrix in which A is a block matrix, where the blocks come from group rings and also,
A is not fully determined by the elements appearing in the first row. By applying our
construction over F2 +uF2 and by employing the extension method for codes, we were
able to construct new extremal binary self-dual codes of length 68. Additionally, by
employing a generalised neighbour method to the codes obtained, we were able to con-
struct many new binary self-dual [68,34,12]-codes with the rare parameters
; and in : In particular, we find 92 new binary
self-dual [68,34,12]-codes
The Entrepreneurial Personality: A Social Construction, 2nd ed., Book Review
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Transitions and student wellbeing in higher education: Exploring the role of Independent Learning Skills
Get PDFThe number of reported mental health issues amongst university students continues to rise, affecting student attainment and progression. Within this context, this study explores students’ experiences of wellbeing during transition to university, specifically exploring the under-researched area of how Independent Learning Skills (ILS) and wellbeing interrelate. A novel conceptual framework combining aspects of ILS and wellbeing was constructed which then informed semi-structured interviews with university business school students and a Template Analysis. The study found a variety of ways in which the development of ILS and student wellbeing can be helped and hindered during transition to university, for example, how student and university practices appear to affect ILS and wellbeing. As such, this study sits in contrast to previous research in combining two areas not typically combined to examine student transition, offering new practical insights into supporting students.
Key contributions that have been made as a result of this research include a deeper understanding of the relationship between specific ILS skills and specific elements of wellbeing. The experiences that students had were found to be inconsistent relating to academic support and these experiences both positive and negative were shown to mediate the relationship between ILS and wellbeing. Early experiences of the students were shown to have an anchoring effect on ILS and wellbeing, for example not engaging with support offered by their Personal Academic Tutor (PAT) was later shown to have hindered achievements and feelings of wellbeing. The diversity of learning needs and preferences identified from the research was also found to relate to students’ development of ILS and associated feelings of wellbeing. Further research has been identified that seeks to explore the relationship between ILS and wellbeing to specific student outcomes, including student grades, retention and progression outcomes
Cosmopolitan Practical Theology and the Impact of the Norming of Whiteness on Chapel Cosmopolitanism
Get PDFIn the context of increasing cosmopolitanism across the UK many church congregations are becoming increasingly ethnically diverse, creating what I am calling ‘chapel cosmopolitanism’. This lived experience of congregations calls for a Cosmopolitan Practical Theology. I use Nowicka and Rovisco’s definition (2009:2) of cosmopolitanism as “A practice which is apparent in things that people do and say to positively engage with the ‘otherness of the other’”. From my professional experience I outline the factors that make a Cosmopolitan Practical Theology and argue for a positive engagement with the ‘otherness of the other’ in order to live out the Gospel imperative to ‘Love your neighbour as yourself’.
In an ethnographic study of the chapel cosmopolitanism of one particular church, I observed the complex layers of interpersonal dynamics within one congregation. In particular I engaged with the work of Marti (2010) on ‘havens’, and also the work of Jagessar (2015) on ‘intercultural habit’, observing the inter-play between the needs for both of these practices. Using a multi-method approach I began to notice the reluctance of older White participants who chose not to be interviewed. While recognizing the need for both ‘havens’ and ‘intercultural habit’ my fieldwork data showed me that, while all my participants had these two needs, yet the need for havens of their own was not recognized by many of my White participants. This White privileging of their own experience as the ‘norm’ prevented the ‘mutual inconveniencing’ that Jagessar considers to be an essential component of intercultural habit.
After consideration of the impact of the invisibility of White privilege within this particular congregation, I conclude that the norming of Whiteness becomes an obstruction to the development of a Cosmopolitan Practical Theology. In my conclusion I spell out some of the implications of my research for church life, Practical Theology and my own practice
Pedagogies for developing undergraduate ethical thinking within geography
No full textThis chapter initially defines the goals of teaching ethics to geography undergraduates, before outlining what a holistic programme approach might look like. This includes identification of seven different contexts, inside and outside the curriculum, when ethical issues might be encountered by geography students; a list which may act as a useful guide for tutors considering teaching ethics for the first time. Whatever specific approaches to teaching ethics are adopted, the next section emphasizes the value of giving students the opportunity to recognize, review, and respond to topics and experiences. Within this context, the value of pursuing non-didactic teaching approaches, the importance of providing a consistent theoretical framework for reviewing ethical problems, and the likely impact of encouraging ongoing personal reflection are discussed. These pedagogic strategies are illustrated further through a case study detailing engagement with ethical issues within small group tutorial discussions using tutor- and student-authored scenarios
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