| 1. |
- Grinnemo, Karl-Henrik, et al.
(författare)
-
Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart
- 2008
-
Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 26:7, s. 1850-1857
-
Tidskriftsartikel (refereegranskat)abstract
- In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.
|
|
| 2. |
- Hao, Xiaojin, et al.
(författare)
-
Angiogenic effects of sequential release of VEGF-A(165) and PDGF-BB with alginate hydrogels after myocardial infarction
- 2007
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 28, s. 612-612
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A(165) (VEGF-A(165)) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction. Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with I-125-labelled VEGF-A(165) and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A(165), PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice. Results: Alginate gets were capable of delivering VEGF-A(165) and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A(165). Sequential growth factor administration led to a higher density of alpha-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration. Conclusions: The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A(165) and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.
|
|
| 3. |
- Hao, Xiaojin, et al.
(författare)
-
Myocardial angiogenesis after plasmid or adenoviral VEGF-A(165) gene transfer in rat myocardial infarction model
- 2007
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 73:3, s. 481-487
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare gene transfer of plasmid (P) and adenovirus (Ad) encoding human vascular endothelial growth factor-A(165) (hVEGF-A(165)) angiogenic efficacy and adverse effects as regards apoptosis and ectopic expression of the transgene in a rat myocardial infarction model. Methods: Myocardial infarction was provoked in Fisher rats. One week later, PhVEGF-A(165), PLacZ, AdhVEGF-A(165), or AdLacZ was transferred intramyocardially along the border of the myocardial infarction. hVEGF-A expression was detected with ELISA. Myocardial vessel density was analyzed 1 and 4 weeks after gene transfer. Apoptosis was detected by TUNEL staining. Cardiac function was assessed with Tissue Doppler Velocity Imaging. Results: Although AdhVEGF-A(165) had substantially higher myocardial hVEGF-A expression than PhVEGF-A(165), AdhVEGF-A(165) and PhVEGF-A(165) induced angiogenic effects to a similar extent with maintained increased arteriolar density after 4 weeks of gene transfer (p < 0.05). The two treatments also improved left ventricular function similarly. Adenoviral gene transfer induced a higher number of TUNEL positive cells than plasmid (p < 0.02). Ectopic expression of the transgene was present with both vectors but substantially higher after adenoviral gene transfer. Conclusions: AdhVEGF-A165 has no obvious angiogenic advantage over PhVEGF-A165 but more side effects at least in a rat myocardial infarction model. This indicates that PhVEGF-A(165) might be more applicable for therapeutic angiogenesis than AdhVEGF-A(165).
|
|
| 4. |
- Sadigh, Bita, et al.
(författare)
-
The ischemic preconditioning effect of adenosine in patients with ischemic heart disease
- 2009
-
Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans. AIMS: We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function. MATERIALS AND METHODS: We studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic. RESULTS: PSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001) and low-dose adenosine infusion (P = 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS). CONCLUSION: Low-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.
|
|
