Clinical safety of bovine intra-ovarian application of allogeneic mesenchymal stem cells

Abstract

A basic premise of reproductive physiology is that females have a finite and non-renewable stock of germinative cells, which results in a decrease in reproductive capacity over time. For female bovines, a further factor associated with this decrease is follicular puncture (ovum pickup - OPU), a technique widely used for production of embryos in vitro. As such, it is necessary to seek therapeutic or preventive options for fertility problems, and one potential option is treatment with mesenchymal stem cells (MSC), which exercise a paracrine effect in combating inflammatory and degenerative processes. However, as important as evaluating the efficacy of such treatments is an evaluation of safety. In this context, the current study was carried out with the application of 2.5 x 106 allogenic MSC derived from adipose tissue, to the ovarian cortex of healthy nelore (n = 5) and girolando (n = 5) cows. The animals were subsequently evaluated by ultrasonography, clinical examination, number of viable oocytes collected, and rate of embryo production. None of the animals presented any clinical alteration or any alteration on ultrasonography after receiving the MSC. Furthermore, comparison between the number of viable oocytes, embryos produced, and rate of embryo production before and after MSC application did not show a difference. Based on these data, it can be concluded that intraovarian application of 2.5 x 106 adipose-derived MSC is safe, and this technique represents a potential for study as a therapy in cases of ovarian degeneration or lesions.