Transamniotic Stem Cell Therapy (TRASCET) Improves Fetal Outcomes in a Model of Intrauterine Growth Restriction (IUGR)
Ashlyn E Whitlock, MD1,2, Kamila Moskowitzova, MD1,2, Ina Kycia, PhD1,2, David Zurakowski, PhD1,2, Dario O Fauza, MD, PhD1,2
1Boston Childrens Hospital, Boston, MA; 2Harvard Medical School, Boston, MA
Background: We sought to determine whether transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) could improve fetal outcomes in intrauterine growth restriction (IUGR).
Methods: Fetuses (n=155) from twelve Sprague-Dawley dams were exposed to 12-hour hypoxia (10.5% O2) cycles from gestational-day 15 (E15) until term (E21). One group remained untreated (n=42 fetuses). Three groups received volume-matched intra-amniotic injections of either saline (sham, n=34), or amniotic fluid-derived MSCs, either in native state (TRASCET, n=36) or “primed” by exposure to inflammatory cytokines (TRASCET-Primed, n=43). Normal fetuses served as additional controls (n=30). Multiple morphometric and ELISA analyses were conducted at term.
Results: Placental efficiency was significantly decreased in untreated and sham (p=0.002 to <0.001) but normalized in both TRASCET groups. Brain weights were significantly decreased in the untreated and sham groups (p<0.001) but significantly increased in both TRASCET groups (p=0.003, <0.001). TRASCET-Primed had lower brain levels of pro-inflammatory TNF-? and IL-1? compared to untreated and sham (both p<0.001-0.017). Fetal heart to body weight ratio was increased in both the sham and untreated groups (p<0.001 for both) but normalized in both TRASCET groups (p=0.275, 0.069). Cardiac BNP levels were significantly decreased from sham and untreated in both TRASCET groups (p<0.0001-0.005). Lung TGF-? and Endothelin-1 levels were significantly increased in both sham and untreated groups (p<0.001, 0.003) but normalized in both TRASCET groups (p=0.303-.928).
Conclusion: TRASCET reverses core effects of IUGR in a rat model, apparently by reducing placental inflammation. Further study into this novel approach for the treatment of this disease is warranted.
Back to 2022 Program