A Multimodal Scaffold for SDF1 Delivery Improves Cardiac Function in a Rat Subacute Myocardial Infarct Model.

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI.

Association of CD80 and CD86 expression levels with disease status of Visna/Maedi virus infected sheep.

In small ruminant lentivirus infections, cellular immune responses are diminished in clinically affected animals. The underlying mechanisms for this are unknown. In this study, we tested the hypothesis that alterations in expression of the co-stimulatory molecules B7-1 and B7-2 are involved in infections with Visna/Maedi virus (VMV), the prototype lentivirus of sheep. We studied B7 expression levels ex vivo in peripheral blood mononuclear cells (PBMCs), determining B7 RNA levels by real time reverse transcriptase polymerase chain reaction in asymptomatic as well as clinically affected VMV-seropositive sheep. The levels of both B7 molecules were increased in VMV-seropositive asymptomatic sheep. However, in VMV clinically affected sheep, the level of CD80 (but not CD86) was low compared with the level in uninfected sheep (p < 0.05). CD80 and CD86 RNA levels were associated with the ability of PBMCs to respond to VMV gag antigens (p14, p17, and p25) by proliferation, with most seropositive asymptomatic sheep showing positive proliferative responses but clinically affected sheep showing no response. The response to p25 in clinically affected animals was increased by the addition of interleukin-2 to the cultures. Decreased recall responses to unrelated antigens (assessed by production of interferon-gamma) were also found in clinically affected sheep. Thus, among seropositive sheep, decreased B7-1 (CD80) RNA levels and diminished antigen-specific cellular immune responses in PBMCs point to a VMV disease status, whereas increased CD80 and CD86 levels and augmented cellular responses are linked to asymptomatic infection.

Towards the modelling of ageing and atherosclerosis effects in ApoE(-/-) mice aortic tissue.

The goal of this work consists in a quantitative analysis and constitutive modelling of ageing processes associated to plaque formation in mice arteries. Reliable information on the characteristic evolution of pressure-stretch curves due to the ageing effects is extracted from previous inflation test experiments. Furthermore, characteristic age-dependent material parameters are identified on the basis of a continuum-mechanics-based parameter optimisation technique. The results indicate that the aorta-stiffness of the healthy control mice remains basically constant irrespective of the diet-time and age. In contrast, significant differences exist within the material response and in consequence within the material parameters between the ApoE(-/-) and the control mice as well as for the different locations over the aorta which is underlined by our experimental observations. With regard to the temporal evolution of the material parameters, we observe that the material parameters for the ApoE(-/-) mice aortas exhibit a saturation-type increase with respect to age.

Epicardial delivery of collagen patches with adipose-derived stem cells in rat and minipig models of chronic myocardial infarction.

Although transplantation of adipose-derived stem cells (ADSC) in chronic myocardial infarction (MI) models is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of this study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. With that purpose, chronically infarcted Sprague-Dawley rats (n = 58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed 4 months after transplantation. In addition, Göttingen minipigs (n = 18) were subjected to MI and then transplanted 2 months later with CS or CS seeded with autologous minipig ADSC (CS-pADSC). Functional and histological assessments were performed 3 months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Moreover, transplantation of CS-pADSC in the pre-clinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling.