Background: In the placenta, mesenchymal stem/stromal cells (MSC) are located in a perivascular niche and exhibit a tendency to differentiate into endothelial cells, suggesting a role in vascular development. Animal studies have shown that transplanted MSC stimulate angiogenesis in several different tissues. Thus, placental MSC may be therapeutically useful in pregnancy disorders such as intrauterine growth restriction where placental vascularisation is insufficient. This study aimed to assess the behaviour of transplanted MSC in human placental explants in vitro.
Methods: MSC isolated from first trimester and term placentae were characterised by flow cytometry.MSC were labelled with CMRA and injected into first-trimester or term placental villous explants, or between placental villi. MSC viability post-transplantation was assessed by counterstaining explants with CMFDA after 48 or 96hrs in culture. Fixed explants were vibratome sectioned and imaged by confocal microscopy.
Results: Following transplant, MSC migrated from the injection site to the villus tips and in some instances surrounded placental vessels. 89.1% (±3.7% SE, n=9 explants, 3 placentae) of first-trimester MSC injected into first-trimester explants were viable after 48hrs of culture. Term MSC injected into blood vessels were only viable after 48hrs if they migrated out of the vessels into the villus stroma (51.8% ±6.9% SE, n=9 explants, 3 placentae). After 96 hours, no viable MSC were evident within term or first-trimester explants, nor was the explant tissue itself viable. When transplanted between placental villi, MSC formed cellular aggregates from which some MSC appeared to cross into the villus stroma.
Conclusions: MSC can be successfully transplanted into placental villi, and MSC transplanted into the intervillous space can cross into the placenta. However, MSC viability in this model is limited by the overall viability of the explants, highlighting the need to use an in vivo model to study MSC behaviour over a longer timeframe.