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- Lin, CH, et al.
(författare)
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In Vitro Study of Human Immune Responses to Hyaluronic Acid Hydrogels, Recombinant Spidroins and Human Neural Progenitor Cells of Relevance to Spinal Cord Injury Repair
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor cells (hNPCs). Here, we analyzed short- and long-term in vitro activation of immune cells in human peripheral blood mononuclear cells (hPBMCs) cultured with/without recombinant spidroins, HA hydrogels, and/or allogeneic hNPCs to assess potential host–donor interactions. Viability, proliferation and phenotype of hPBMCs were analyzed using NucleoCounter and flow cytometry. hPBMC viability was confirmed after exposure to the different biomaterials. Short-term (15 h) co-cultures of hPBMCs with spidroins, but not with HA hydrogel, resulted in a significant increase in the proportion of activated CD69+ CD4+ T cells, CD8+ T cells, B cells and NK cells, which likely was caused by residual endotoxins from the Escherichia coli expression system. The observed spidroin-induced hPBMC activation was not altered by hNPCs. It is resource-effective to evaluate human compatibility of novel biomaterials early in development of the production process to, when necessary, make alterations to minimize rejection risk. Here, we present a method to evaluate biomaterials and hPBMC compatibility in conjunction with allogeneic human cells.
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| 2. |
- Roemer, Frank W., et al.
(författare)
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Development of MRI-defined structural tissue damage after anterior cruciate ligament injury over 5 Years : The KANON Study
- 2021
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Ingår i: Radiology. - 0033-8419. ; 299:2, s. 383-393
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Tidskriftsartikel (refereegranskat)abstract
- Background: MRI is used to evaluate structural joint changes after anterior cruciate ligament (ACL) injury, but no long-term data are available for comparing different treatment approaches. Purpose: To describe structural joint damage with MRI over a 5-year period in the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) study and to compare frequencies of such tissue damage for a nonsurgical versus a surgical treatment strategy. Materials and Methods: In this secondary analysis of a prospective trial (ISRCTN 84752559), 119 participants with an acute ACL injury were evaluated. Participants were enrolled from 2002 through 2006, the 2-year follow-up started in 2008, and the 5-year follow-up started in 2011. A 1.5-T MRI examination was performed at baseline and at 2- and 5-year follow-up. MRI scans were read according to a validated scoring instrument. Kruskal-Wallis tests were used to assess whether the frequencies of structural damage differed between the three as-treated groups. Results: Of 119 participants (mean age, 26 years ± 5 [standard deviation]), 91 men were evaluated. At 2- and 5-year follow-up, respectively, 13% (15 of 117) and 13% (15 of 115) of knees showed incident cartilage damage in the medial tibiofemoral joint, 11% (13 of 117) and 17% (20 of 115) of knees showed incident cartilage damage in the lateral tibiofemoral joint, and 4% (five of 117) and 8% (nine of 115) of knees showed incident cartilage damage in the patellofemoral joint. Osteophyte development was seen in 23% (27 of 117) and 29% (33 of 115) of knees in the medial tibiofemoral joint, in 36% (42 of 117) and 43% (49 of 115) of knees in the lateral tibiofemoral joint, and in 35% (41 of 117) and 37% (42 of 115) of knees in the patellofemoral joint. No major differences between the groups were found for incident or worsening cartilage damage, bone marrow lesions, and osteophytes at 2 or 5 years. The rehabilitation-alone group showed less Hoffa-synovitis at 2 (P = .02) and 5 (P = .008) years. Conclusion: Young adults with anterior cruciate ligament injury showed no major difference in frequency of structural tissue damage on MRI scans at 2 and 5 years regardless of treatment. However, the rehabilitation-alone group had less inflammation at 2 and 5 years.
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| 3. |
- Schillemans, Tessa, et al.
(författare)
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Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
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