Effect of Pregnancy on Differentiation Potential of Equine Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) derived from peripheral blood have been recently under attention, not only due to their important immunomodulatory and anti-inflammatory properties to treat injured tissues, but especially for being an excellent alternative source of MSCs in horses, readily available and less invasive. However, the mechanisms involved with the mobilization of these MSCs into the peripheral circulation remains largely unknown. In multiple species, pregnancy and its physiological adaptations on maternal circulation have been associated with increased MSC populations, but to date, there are no reports on this subject in horses. Thus, this study aimed to evaluate the effect of pregnancy on isolation efficiency and differentiation potential of equine MSCs derived from peripheral blood of mares on pre- and post-partum. Sixteen Arabian mares, with age range between 4- 10 years (6.69 ± 1.78 years), clinically healthy and presenting normal pregnancies, had venous blood samples harvested at two time periods: 11th month of gestation, and 1 month after delivery. Blood samples were submitted for in vitro MSC culture, determination of isolation efficiency and proliferation capacity. Cellular characterization was achieved through trilineage differentiation and immunophenotyping, and finally plasmatic concentrations of gestational-related hormones (cortisol, DHEA, progesterone, DHP, 20αDHP, allopregnanolone and estrone sulfate) were measured. Pregnancy was associated with higher isolation efficiency, and faster proliferation was noted with lower levels of metabolites such as DHP, 20αDHP and allopregnanolone. Post-partum findings, such as elevated DHEA concentrations and high cortisol: DHEA ratio, were presumed to negatively affect the MSCs isolation efficiency and proliferation capacity. Therefore, this study suggests that pregnant mares exhibit increased number of MSCs into the peripheral circulation, and these cells present higher proliferation ability. Further investigation is still needed to determine the pathways involved in such cell mobilization and proliferation.