Bovine peripheral blood MSCs chemotax towards inflammation and embryo implantation stimuli

• Published in: Journal of cellular physiology Vol. 236; no. 2; pp. 1054 - 1067
• Main Authors: Calle, Alexandra, Gutiérrez‐Reinoso, Miguel Ángel, Re, Michela, Blanco, Javier, De la Fuente, Julio, Monguió‐Tortajada, Marta, Borràs, Francesc Enric, Yáñez‐Mó, María, Ramírez, Miguel Ángel
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01-02-2021
• Subjects: Alkaline phosphatase; Biomedical materials; Blood circulation; Bone marrow; Cell migration; Cell proliferation; Chemotaxis; Cytokines; embryo implantation; Embryos; Endometrium; granulocyte colony‐stimulating factor; Heterogeneity; Immune response; Immune system; Immunological tolerance; Immunoregulation; Implantation; Inflammation; Interferon; Lymphocytes; Lymphocytes T; Mesenchymal stem cells; Mesenchyme; Peripheral blood; peripheral blood mesenchymal stem cells; Pregnancy; Regenerative medicine; Secretome; Stem cells; Stimuli; Tissue engineering; Trophectoderm
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29915

Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine because of their multipotential and immunoregulatory capacities, while in early pregnancy they could participate in the immunotolerance of the mother towards the embryo. Peripheral blood constitutes an accessible source of MSCs. We successfully isolated peripheral blood MSC (pbMSCs) lines, with or without previous bone marrow mobilization. All pbMSCs lines obtained in both conditions presented classical MSC markers and properties, alkaline phosphatase activity and multipotent capacity to differentiate among adipogenic, osteogenic or chondrogenic lineages, and suppressed the proliferation of T cells. pbMSCs showed migratory capacity without cytokine stimulation while increasing their migration rate in the presence of inflammatory or embryo implantation stimuli. Interestingly, in contrast to MSCs derived from endometrial tissue, three pbMSCs lines also showed increased migration towards the IFN‐τ implantation cytokine. Moreover, the secretome produced by an early implantation stage embryonic trophectoderm cell line showed a chemoattractant effect in pbMSCs. Our results suggest that circulating MSCs are present in the peripheral blood under healthy conditions. The fact that both the inflammation and implantation signals induced pbMSCs chemotaxis highlights MSC heterogeneity and suggests that their migratory capacity may differ according to their tissue of origin and would suggest the possible active recruitment of MSCs from bone marrow during pregnancy to repress the immune response to prevent the embryo rejection by the maternal organism.
Bovine mesenchymal stem cells (MSCs) circulate in the peripheral blood under normal conditions. Inflammation/implantation signals and signals from embryonic trophectoderm induce the chemotaxis of peripheral blood MSC and could be suggestive of a bone marrow origin of endometrial mesenchymal stem cells during bovine pregnancy that would help in maintaining the immune response at a minimum to prevent the embryo rejection by the maternal organism. Our data also highlight the heterogeneity of MSCs derived from different tissues in terms of their migratory capacity.