Comparative Effects on Fetal Hematopoiesis and Placental Inflammation from Mesenchymal and Hematopoietic Stem Cells as Agents of Transamniotic Stem Cell Therapy (TRASCET) in a Syngeneic Model of Intrauterine Growth Restriction

Purpose We compared transamniotic stem cell therapy (TRASCET) using either mesenchymal (MSCs) or hematopoietic (HSCs) stem cells on fetal hematopoiesis in a syngeneic model of intrauterine growth restriction (IUGR). Methods Lewis dams exposed to cycling hypoxia (10.5% O2) in late gestation had their fetuses (n=83) either receiving no intervention (untreated; n=9), or intra-amniotic injections of either HSCs (HSC; n=34), MSCs primed to an enhanced anti-inflammatory phenotype (primed-MSC; n=28), or saline (sham; n=12). Normal controls (n=18) were also studied. Complete peripheral blood counts and placental ELISA for inflammation and angiogenesis markers were performed at term. Results Overall survival from hypoxia was 41% (34/83). Red blood count (RBC), hematocrit (Hct) and hemoglobin levels (Hb) were all significantly decreased from normal in all hypoxia groups. TRASCET with primed-MSC had significantly higher RBC, Hct, and Hb levels than sham (p=0.01-0.03, pairwise), though not than untreated (which had no surgical blood loss). The HSC group had only significantly higher Hb levels than sham (p=0.005). TRASCET with primed-MSC had significantly lower levels of placental TNF-α than sham (p=0.04), but not untreated. Conclusions: MCSs seem more effective than HSCs in enhancing hematopoiesis when used as donor cells for TRASCET in a syngeneic model of IUGR. Level of Evidence N/A (animal and laboratory study)