Exploring the potential of placental mesenchymal stem cell transplantation into human placentae

Abstract

Introduction: Intrauterine growth restriction (IUGR) is a placental disorder associated with impaired vascular function that affects up to 10% of pregnancies. IUGR fetuses have increased risks of perinatal mortality and postnatal morbidity, but currently there are no effective therapies to treat IUGR. Mesenchymal stem cells (MSC) are multipotent cells present in the placenta, which have demonstrated angiogenic and immunomodulatory functions following transplantation into different tissues. However, there has been no previous work investigating the potential of placental MSC transplantation into placental tissues to treat placental disorders such as IUGR. Aims: In order to understand the potential of placental MSC transplantation for the treatment of IUGR, this work aimed to examine the survival and migration of placental MSC following transplantation into placental tissues in vitro. Methods: MSC were isolated from first trimester and term placentae. MSC were characterised using multi-colour flow cytometry to confirm they expressed MSC markers (CD73, CD90 and CD105) and did not express markers of contaminating cells (CD31, CD34 and CD45). Characterised MSC were fluorescently labelled and injected into placental explants. The viability and migration of transplanted MSC were assessed following 48 or 96 hours in culture. Vibratome-sectioned explants were imaged using confocal microscopy. Results: MSC expressed CD73 and CD90, and did not express CD31, CD34 or CD45. MSC were initially phenotyped as CD105 negative, but further experiments revealed that this was due to trypsin exposure. Transplanted MSC migrated through the placental villous stroma, formed cellular networks and assumed potential perivascular positions. Transplanted MSC exhibited transendothelial migration and appeared able to cross the syncytiotrophoblast. Both transplanted placental MSC and host explant tissue were viable after 48 hours, but not 96 hours in culture. Conclusions: Placental MSC express characteristic MSC markers, and CD105 expression is influenced by trypsin exposure. MSC can be successfully transplanted into placental tissues, but the viability of transplanted MSC is limited by the overall viability of the explant culture system. These results demonstrate that the delivery of MSC to pathological placentae is plausible.