Transamniotic stem cell therapy (TRASCET) for intrauterine growth restriction (IUGR): A comparison between placental and amniotic fluid donor mesenchymal stem cells

Purpose: Transamniotic stem cell therapy (TRASCET) with donor mesenchymal stem cells (MSCs) has been shown experimentally to reverse central effects of intrauterine growth restriction (IUGR). We sought to compare amniotic-fluid and placenta-derived MSCs (afMSCs and pMSCs, respectively) as TRASCET donor cells in a murine IUGR model. Methods: Pregnant Sprague-Dawley dams (n = 8) were exposed to alternating 12-hour hypoxia (10.5% O 2 ) cycles, starting on gestational day 15 (E15; term = E21-22). On E17, fetuses (n = 100) were divided into four groups. An untreated group had no further manipulations (n = 24). Three groups received volume -matched intra-amniotic injections of either saline (sham; n = 27), or suspensions of afMSCs (n = 24), or pMSCs (n = 25). Normal fetuses served as controls (n = 21). All infused MSCs consisted of syngeneic Lewis rat cells phenotyped by flow cytometry and GFP-labeled. At term, fetal and placental morphometrics were calculated, and placental TNF-alpha levels were determined by ELISA. Statistical comparisons were by Fischer's T-test or Wilcoxon rank sum test (p <= 0.05). Results: Overall survival of the hypoxic groups was 83% (83/100). Compared to normal, maternal-adjusted fetal weights were significantly decreased in all hypoxia groups (pairwise p < 0.001), however only the afMSC group showed higher adjusted-fetal weights than sham (p < 0.001). Placental efficiency was de-creased in untreated, sham, and pMSC groups (p < 0.001-0.056) but normalized in the afMSC group (p = 0.205). Maternal-adjusted placental weights were lower than normal in all hypoxia groups (p < 0.001-0.045), except for the pMSC group (p = 0.387). Conclusions: Amniotic fluid-derived mesenchymal stem cells are superior to their placenta-derived coun-terparts in transamniotic stem cell therapy for intrauterine growth restriction in a rat model. Level of Evidence: Basic/Translational science. (c) 2022 Elsevier Inc. All rights reserved.