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- Al-Saadi, Jonathan, et al.
(författare)
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Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
- 2024
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Ingår i: Molecular therapy. Methods & clinical development. - : Elsevier BV. - 2399-6951 .- 2329-0501. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.
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- Fältström, Anne, et al.
(författare)
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Normative values and changes in range of motion, strength, and functional performance over 1 year in adolescent female football players : Data from 418 players in the Karolinska football Injury Cohort study.
- 2022
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Ingår i: Physical Therapy in Sport. - : Elsevier. - 1466-853X .- 1873-1600. ; 58, s. 106-116
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study normative values of range of motion (ROM), strength, and functional performance and investigate changes over 1 year in adolescent female football players.DESIGN: Cross-sectional.PARTICIPANTS: 418 adolescent female football players aged 12-17 years.MAIN OUTCOME MEASURES: The physical characteristic assessments included (1) ROM assessment of the trunk, hips, and ankles; (2) strength measures (maximal isometric and eccentric strength for the trunk, hips, and knees, and strength endurance for the neck, back, trunk and calves), and (3) functional performance (the one-leg long box jump test and the square hop test).RESULTS: Older players were stronger, but not when normalized to body weight. Only small differences in ROM regarding age were found. ROM increased over 1 year in most measurements with the largest change in hip external rotation, which increased by 6-7° (Cohen's d = 0.83-0.87). Hip (d = 0.28-1.07) and knee (d = 0.38-0.53) muscle strength and the square hop test (d = 0.71-0.99) improved over 1 year.CONCLUSIONS: Normative values for ROM and strength assessments of neck, back, trunk, hips, knees, calves and ankles are presented for adolescent female football players. Generally, fluctuations in ROM were small with little clinical meaning, whereas strength improved over 1 year.
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