Priorities and opportunities for advocacy in SCI: An international web-based review.

CONTEXT: For the growing number of people with spinal cord injuries worldwide, advocacy organizations are an invaluable resource of information and education during recovery and rehabilitation. OBJECTIVE: To examine the structure, information, and accessibility of websites from international organizations that serve and advocate for individuals with SCI. METHODS: We performed a content analysis of information available from SCI organizations returned from a Google search. We used search terms relevant to SCI and advocacy and applied them to top-level domains for the G20 countries. Organizations that provide services or advocate for people with SCI with English-language websites were included; organizations focused on research, fundraising, clinical care, interprofessional knowledge exchange, or other neurological conditions were excluded. Accessibility, in terms of ease of use to information about participation, was assessed using a 3-point scale. RESULTS: We identified SCI organizations from 27 different countries across six regions: Africa (N = 4), Asia (N = 5), Europe (N = 27), Middle East (N = 1), North America (N = 12), and Oceania (N = 11). Across these, six categories of resources and services are covered: (1) education, (2) physical health, (3) external, (4) peer support, (5) mental health, and (6) financial and legal. Eleven organizations indicate specific engagement with research or clinical trials. Four websites provided highly accessible information (rank = 3) about participation in research. CONCLUSION: The SCI organizations identified in this study offer resources that largely pertain to education and physical health services and strategies. Information about clinical trials and SCI research studies are easily accessible on the websites of the limited number of organizations offering avenues for participation.

Ethics and accountability for clinical trials.

In May 2023, a disclaimer posted on ClinicalTrials.gov dismisses accountability for the accuracy of registered information. For spinal cord injury, inconsistencies in intervention classification, phase designation, and lack of study protocols and results threaten the integrity of the database and put users at risk. An investment in what the resource should be rather than what it is not will give it the authority commensurate with the requirements for its regulatory use and informed decision-making for prospective trial participants.

Vascular Dysfunction after Modeled Traumatic Brain Injury Is Preserved with Administration of Umbilical Cord Derived Mesenchymal Stromal Cells and Is Associated with Modulation of the Angiogenic Response.

Vascular dysfunction arising from blood-brain barrier (BBB) breakdown after traumatic brain injury (TBI) can adversely affect neuronal health and behavioral outcome. Pericytes and endothelial cells of the neurovascular unit (NVU) function collectively to maintain strict regulation of the BBB through tight junctions. Secondary injury mechanisms, such as pro-angiogenic signals that contribute to pericyte loss, can prolong and exacerbate primary vascular injury. Human umbilical cord perivascular cells (HUCPVCs) are a source of mesenchymal stromal cells (MSCs) that have been shown to reduce vascular dysfunction after neurotrauma. We hypothesized that the perivascular properties of HUCPVCs can reduce vascular dysfunction after modeled TBI by preserving the pericyte-endothelial interactions. Rats were subjected to a moderate fluid percussion injury (FPI) and intravenously infused with 1,500,000 HUCPVCs post-injury. At acute time points (24 h and 48 h) quantitative polymerase chain reaction (qPCR) analysis demonstrated that the gene expression of angiopoietin-2 was increased with FPI and reduced with HUCPVCs. Immunofluorescent assessment of RECA-1 (endothelial cells) and platelet-derived growth factor receptors (PDGFR-ß) (pericytes) revealed that capillary and pericyte densities as well as the co-localization of the two cells were decreased with FPI and preserved with HUCPVC administration. These acute HUCPVC-mediated protective effects were associated with less permeability to Evan's blue dye and increased expression of the tight junction occludin, suggesting less vascular leakage. Further, at 4 weeks post-injury, HUCPVC administration was associated with reduced anxiety and decreased ß-amyloid precursor protein (ß-APP) accumulation. In summary, HUCPVCs promoted pericyte-endothelial barrier function that was associated with improved long-term outcome.

Axon Degeneration Is Rescued with Human Umbilical Cord Perivascular Cells: A Potential Candidate for Neuroprotection After Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to delayed secondary injury events consisting of cellular and molecular cascades that exacerbate the initial injury. Human umbilical cord perivascular cells (HUCPVCs) secrete neurotrophic and prosurvival factors. In this study, we examined the effects of HUCPVC in sympathetic axon and cortical axon survival models and sought to determine whether HUCPVC provide axonal survival cues. We then examined the effects of the HUCPVC in an in vivo fluid percussion injury model of TBI. Our data indicate that HUCPVCs express neurotrophic and neural survival factors. They also express and secrete relevant growth and survival proteins when cultured alone, or in the presence of injured axons. Coculture experiments indicate that HUCPVCs interact preferentially with axons when cocultured with sympathetic neurons and reduce axonal degeneration. Nerve growth factor withdrawal in axonal compartments resulted in 66 ± 3% axon degeneration, whereas HUCPVC coculture rescued axon degeneration to 35 ± 3%. Inhibition of Akt (LY294002) resulted in a significant increase in degeneration compared with HUCPVC cocultures (48 ± 7% degeneration). Under normoxic conditions, control cultures showed 39 ± 5% degeneration. Oxygen glucose deprivation (OGD) resulted in 58 ± 3% degeneration and OGD HUCPVC cocultures reduced degeneration to 34 ± 5% (p < 0.05). In an in vivo model of TBI, immunohistochemical analysis of NF200 showed improved axon morphology in HUCPVC-treated animals compared with injured animals. These data presented in this study indicate an important role for perivascular cells in protecting axons from injury and a potential cell-based therapy to treat secondary injury after TBI.

In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells.

Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting that in vitro predifferentiation could be a potential strategy to increase their effectiveness in vivo.

Canine plasminogen: spectral responses to changes in 6-aminohexanoate and temperature.

We studied the near UV absorption spectrum of canine plasminogen. There are 19 tryptophans, 19 phenylalanines and 34 tyrosines in the protein. 4th derivative spectra optimized for either tryptophan or tyrosine give a measure of the polarity of the environments of these two aromatic amino acids. Plasminogen at temperatures between 0 degrees C and 37 degrees C exists as a mixture of four conformations: closed-relaxed, open-relaxed, closed-compact, and open-compact. The closed to open transition is driven by addition of ligand to a site on the protein. The relaxed to compact transition is driven by increasing temperature from 0 degrees C to above 15-20 degrees C.When the conformation of plasminogen is mainly closed-relaxed, the 4th derivative spectra suggest that the average tryptophan environment is similar to a solution of 20% methanol at the same temperature. Under the same conditions, 4th derivative spectra suggest that the average tyrosine environment is similar to water. These apparent polarities change as the plasminogen is forced to assume the other conformations. We try to rationalize the information based on the known portions of the plasminogen structure.