María Norte Muñoz¹

(1) Alhama de Murcia, 30840, España (Región de Murcia)

Most preclinical studies in cell therapy are performed in animal models of xenotransplantation which could lead to an immune reaction what it may have an influence in therapeutic efficiency. Particularly, mesenchymal stromal cells are an excellent source of stem cells from adult tissues and they have neuroprotective and immunomodulatory properties. However, for a therapeutical use transplantation must be safe. Toxicity assays are scarce thus, we have analyzed in vivo the retinal microglial reaction to xenograft of adipose derived mesenchymal estromal cells into the vitreous body.

A dose of 20,000 cells/eye from primary culture of fluorescent C57/BL6 mice (AdMEC-GFP) was administered into the right vitreous chamber of Sprague Dawley rats. Animals were sacrificed 3, 7 and 45 days after the injection. Intact retinas+vehicle matched groups were used as controls. Four retinas from each group were suitably prepared for cryostat cross sections and six retinas were flatmounte. Microglia and macroglial cells were immunodetected with antibodies against Iba1 and GFAP/Vimentin respectively and morphologically analyzed.

AdMEC-GFP remained in the vitreous up to 45 days after the transplant, without integrating in the retina. At the shortest time points, 3- and 7-days post-transplant, microglia cells are highly activated showing and ameboid morphology and macroglial cells, astrocytes and Müller cells, exhibit an upregulation of GFAP and Vimentin expression. At 45-days port transplant, microglial and macroglial activation persists, furthermore it could be an increased reaction compared to previous time points.

The intravitreal xenotransplant of induces a rapid and persistent activation of retinal microglial and macroglial cells.