Page 107 - Magnesium-based supports for stem cell therapy of vascular disease - Mónica Echeverry Rendón

PLASMA ELECTROLYTIC OXIDIZED MAGNESIUM ADVERSELY INFLUENCES VASCULAR CELLS TYPES BUT NOT MESENCHYMAL CELLS AND MONOCYTES
genes COL4A1 and FN1 that we observed, is particularly relevant for fast arterial repair, because these genes en- code important constituents of the basal membrane. Basal membrane deposition is essential for the re-endothe- lialization of arterial lesions especially after placing of stents. Nevertheless, the surface-coatings require further improvement because released components were cytotoxic to endothelial cells and also compromised pre-es- tablished vascular networks in vitro. However, our experiments were all performed under static conditions which might be harsher compared to intra-arterial conditions after stenting. Then, the high flow rate on the luminal side and the interstitial flow between stent in arterial wall, probably quickly dispose of leachables. Currently, ex vivo and in vivo experiments are in progress to investigate this presumption.
The combination of biomaterials as scaffolds to successfully deliver ASCs [44][45][46] is generally done in three- dimensional scaffolds. Arterial repair, however, requires no more than the ‘two-dimensional’ delivery of ASC to the plane of the lesion to accelerate and stimulate the local response of repair by co-helper cells like endothelium cells. Destruction of pre-established networks of ASC and HUVEC showed that endothelial cells are sensitive to high(er) Mg2+ concentrations which indicates that once the degradation of the material is occurring, the recovery of the tissue may be delayed until the total elimination of the implant. It is important to highlight that all these experi- ments were carried out under static conditions which differ of the real application in which the implants will be constantly exposed to the blood flow where the Mg will be mobilized avoiding its accumulation. Alternatively, damage to the endothelial tissue due to the material can be reduced by the addition of a polymeric coating or an organic compound between the tissue-material interface to mitigate this effect. However, these experiments must be verified under in vivo conditions since, according to several studies, one of the limitations of the evaluation of Mg as implant is that the in vitro models are not precise or representative to predict what may happen in vivo[47] [48][49]. However, the rather ‘harsh’ in vitro settings of our experiments likely exaggerate in vivo conditions. Thus, animal experiments to take the material to the next level of development are warranted.
Conclusions
The aim of this study was to establish a platform of surface-coated Mg loaded with ASC as a treatment of vascular lesion after stent placement. Once the implant is placed, the idea is to count with a dynamic system were the implant degrade slowly under physiological conditions without side effects inducing at the same time the regen- eration of the tissue. This work allow us to identify the concentrations at which cell groups related to the cardio- vascular system can be affected by concentrations of ions of Mg were HUVECs and SMCs showed more sensitivity in comparison with ASCs, fibroblasts and macrophages. An important improvement from a biological perspective was achieved by the using of coated Mg by PEO technique in comparison with bare c.p Mg. Based on these data it was clearly observed that anodized surfaces acts as a protective layer while cell on the untreated samples experi- enced cell death. Even future experiments in in vivo models are required to validate the information obtained in this study, it is considered as a valuable approach to understand the influence of Mg in function and differentiation of ASC and to consider the use of them with Mg as a novel therapeutic option in cardiovascular diseases.
References
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[2] E.G. Lakatta, D. Levy, Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a “set up” for vascular disease, Circulation. 107 (2003) 139–146.
[3] E.G. Lakatta, D. Levy, Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging [4] D. Roy, G. Milot, J. Raymond, Endovascular treatment of unruptured aneurysms, Stroke. 32 (2001) 1998–2004. [5] R. Ross, The pathogenesis of atherosclerosis—an update, N. Engl. J. Med. 314 (1986) 488–500.
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