Dataset Information

Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

ABSTRACT:

Background

Tissue ischemia contributes to necrosis and infection. While angiogenic cell therapies have emerged as a promising strategy against ischemia, current approaches to cell therapies face multiple hurdles. Recent advances in nuclear reprogramming could potentially overcome some of these limitations. However, under severely ischemic conditions necrosis could outpace reprogramming-based repair. As such, adjunctive measures are required to maintain a minimum level of tissue viability/activity for optimal response to restorative interventions.

Methods

Here we explored the combined use of polymerized hemoglobin (PolyHb)-based oxygen nanocarriers with Tissue Nano-Transfection (TNT)-driven restoration to develop tissue preservation/repair strategies that could potentially be used as a first line of care. Random-pattern cutaneous flaps were created in a mouse model of ischemic injury. PolyHbs with high and low oxygen affinity were synthesized and injected into the tissue flap at various timepoints of ischemic injury. The degree of tissue preservation was evaluated in terms of perfusion, oxygenation, and resulting necrosis. TNT was then used to deploy reprogramming-based vasculogenic cell therapies to the flaps via nanochannels. Reprogramming/repair outcomes were evaluated in terms of vascularity and necrosis.

Results

Flaps treated with PolyHbs exhibited a gradual decrease in necrosis as a function of time-to-intervention, with low oxygen affinity PolyHb showing the best outcomes. TNT-based intervention of the flap in combination with PolyHb successfully curtailed advanced necrosis compared to flaps treated with only PolyHb or TNT alone.

Conclusions

These results indicate that PolyHb and TNT technologies could potentially be synergistically deployed and used as early intervention measures to combat severe tissue ischemia.

SUBMITTER: Diaz-Starokozheva L

PROVIDER: S-EPMC7596150 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

Diaz-Starokozheva Ludmila L Das Devleena D Gu Xiangming X Moore Jordan T JT Lemmerman Luke R LR Valerio Ian I Powell Heather M HM Higuita-Castro Natalia N Go Michael R MR Palmer Andre F AF Gallego-Perez Daniel D

Cellular and molecular bioengineering 20200529 5

<h4>Background</h4>Tissue ischemia contributes to necrosis and infection. While angiogenic cell therapies have emerged as a promising strategy against ischemia, current approaches to cell therapies face multiple hurdles. Recent advances in nuclear reprogramming could potentially overcome some of these limitations. However, under severely ischemic conditions necrosis could outpace reprogramming-based repair. As such, adjunctive measures are required to maintain a minimum level of tissue viability ...[more]

PMID: 33184576

Similar Datasets

Project description:Improving health literacy is a national public health priority. Given the context of the COVID-19 pandemic, it is even more critical for health and medical information to be clear and understandable for patients and their families. Clinic-based programs to improve health literacy need to be pragmatic, feasible, and helpful for the implementing clinic and patients. This paper describes the development, implementation, and evaluation of a pragmatic, clinic-based health literacy intervention in a safety-net clinic that serves uninsured and indigent patients. Study methods are guided by a previous pilot study and components recommended for pragmatic interventions. An electronic readiness assessment was distributed to out-patient clinics affiliated with a statewide hospital association. The AskMe3 tool was used for the intervention as it is evidence informed and relatively easy to implement. Implementation included ongoing dialogue between the clinic and the academic research team. Within the implementing clinic, data collected from patients via verbally administered questionnaires was analyzed using descriptive statistics and chi-squares. Interview data collected from the clinic director was analyzed qualitatively for themes. The implementing clinic had some of the lowest average scores of the 34 clinics who participated in the initial readiness assessment. Despite this, they were able to successfully implement the health literacy intervention during a global pandemic. Eighty-eight participants completed patient questionnaires at this clinic. Most patients (96%) agreed the AskMe3 questions helped them talk with the doctor or nurse at their current appointment. Most (99%) also perceived the AskMe3 tool to be very helpful when used in a clinical setting. The clinic director offered that the staff initially thought the intervention would be difficult to implement. However, implementation by clinic volunteers with encouragement and prioritization of health literacy by the clinic director contributed to success. When considering interventions for clinical settings, a pragmatic approach can help with selection and implementation of a program that fits with the realities on the ground. Further, frequent technical assistance can help resolve implementation barriers. Interventions utilizing tools such as AskMe3, because of their simplicity, allow creative solutions to capacity issues for clinics who see a need for health literacy improvements.

Project description:Background: Active restoration is necessary to enhance the recovery of Ostrea edulis reefs, which contribute to many ecosystem services. Restoration can be integrated within aquaculture practices, bringing positive environmental changes while maximising space utilisation. The restoration project MAREA (MAtchmaking Restoration Ecology and Aquaculture) aims to bring back O. edulis in the North-West Adriatic addressing the feasibility of its cultivation. Both successful restoration and sustainable aquaculture require a thorough understanding of the ecological needs, as the requirements of both activities need to be harmonized. Therefore, one of the preliminary activities before embarking on the pilot was the completion of a thorough literature review to identify research directions and gaps required for 'restorative aquaculture', aiming to gather the most up to date O . edulis knowledge on a global and local scale. Methods: Internet (Web of Science, Scopus, Google scholar) and physical resources (libraries) were searched for all available global and local knowledge on O . edulis. Bibliometrix was used to identify the main research topics using keywords, titles, and abstracts analyses. Studies were then manually screened and summarised to extract knowledge specific to restoration and aquaculture. Results: While restoration studies are recent, evidence for the loss of this species and potential causes (and solutions) have been discussed since the end of the 19 th century. While diseases were a leading cause for reef loss, substratum limitation appears to be one of the leading limiting factors for both restoration and aquaculture of O . edulis, and was already mentioned in the early texts that were found. Conclusions: The review highlighted that restoration success and aquaculture feasibility depend upon the crucial stage of settlement. The project 'MAREA' will therefore increase its focus on this stage, both in terms of timing, location, and materials for settlement plates placement.

Project description:BackgroundThere is an urgent need to align human diets with goals for environmental sustainability and population health. The OPTIMAT™-intervention study was developed to implement and evaluate a nutritionally adequate and climate-friendly 4-week lunch menu in Swedish primary schools. This study aimed to explore pupils' and kitchen staff's experiences of the intervention and to identify barriers and facilitators to successful implementation of sustainable school meals.MethodsAn inductive manifest qualitative method was used. Nine focus group discussions (FGDs) were conducted, six with pupils in grades 5 (ages 10-11) and 8 (ages 14-15) (n = 29) and three with kitchen staff (n = 13). Data were analyzed using qualitative content analysis.ResultsFive main categories and 11 subcategories at a manifest level emerged. The five main categories were: 1) Experiences with the new menu, unfolding variations in how the new menu was received and kitchen staff's experiences of working with it; 2) The meaning of diet sustainability, comprising pupils' and kitchen staff's perceptions about diet sustainability as a concept and part of their everyday lives; 3) Factors influencing plant-based food acceptance, covering aspects such as the influence of sensory factors, habits and peer pressure; 4) Opportunities to increase plant-based eating, including factors related to pupils' and kitchen staff's ideas for how to increase plant-based food acceptance; and 5) Need for a supportive environment to achieve dietary change, comprising pupils' and kitchen staff's thoughts on the importance of more knowledge, resources and involvement of stakeholders to eat more plant-based meals in schools.ConclusionsSuccessful implementation of sustainable school meals would require more knowledge among pupils and kitchen staff. Staff also need more training in cooking of sustainable meals. Barriers among pupils could be tackled by introducing new plant-based meals more gradually and by more carefully considering the seasoning, naming and aesthetics of dishes. An increased leadership support for change and involvement of stakeholders from multiple levels within society will be key in the transition to sustainable school meals at scale.Trial registrationThe trial registration for the OPTIMAT™-intervention may be found at clinicaltrials.gov ( NCT04168632 Fostering Healthy and Sustainable Diets Through School Meals (OPTIMAT)).

Project description:BackgroundIntravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice.ResultsCellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes and administered as a single bolus showed to be as effective as a continuous clinical perfusion of free rtPA at equal concentration, without increasing the risk of hemorrhagic transformations or provoking an inflammatory response.ConclusionsThis study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. In addition, this new nanoformulation could simplify the clinical use of rtPA as a single bolus, being easier and less time-consuming in an emergency setting than a treatment perfusion, particularly in stroke patients. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.

Dataset Information

Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

Background

Methods

Results

Conclusions

Publications

Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets