Brain protection by transamniotic stem cell therapy (TRASCET) in a model of intrauterine growth restriction (IUGR) | Animal and laboratory study | Pregnant Sprague-Dawley dams | Alternating 12h hypoxia | Fetus with IUGR | 4 Groups | 1. Untreated | 2. Sham = Only saline | 3. TRASCET = Treated only with Stem Cells (MSC) | 4. TRASCET - Primed = MSC + IFN-γ and IL-1 β | RESULTS | Gross brain weights were significantly increased in both TRASCET groups when compared to untreated and sham (p = 0.003 to < 0.001) | TRASCET-Primed had lower levels of TNF-α and IL-1 β compared to untreated (both p < 0.001) and sham (p = 0.017 // p = 0.011) | Conclusion: TRASCET primed reverses some of the central nervous system effects of intrauterine growth restriction in a rat model | DOI: 10.1016/j.jpedsurg.2022.09.018 | Source: Ashlyn E Whitlock et al. | Department of Surgery, Boston Children's Hospital/ Harvard Medical School, Boston, MA, United States | @StayCurrentMD | @cecilipstick | Cincinnati Children's | Journal of Pediatric Surgery
Brain protection by transamniotic stem cell therapy (TRASCET) in a model of intrauterine growth restriction (IUGR)
Infographic · Mar 2023 · 2 min read
In brief
In brief
Experimental study demonstrates that transamniotic injection of primed mesenchymal stem cells reduces brain inflammation and improves brain growth in a rat model of intrauterine growth restriction. The therapy appears to work by modulating neuroinflammation, offering a potential prenatal intervention for IUGR-related neurodevelopmental complications.
- Transamniotic MSC therapy (TRASCET) significantly increased fetal brain weights in IUGR model compared to untreated controls
- IFN-γ/IL-1β primed MSCs reduced brain TNF-α and IL-1β more effectively than non-primed MSCs in hypoxia-induced IUGR
- TRASCET-Primed achieved significant reduction in neuroinflammation markers vs both untreated and sham groups
- Intra-amniotic MSC delivery may protect fetal brain development by attenuating neuroinflammation in IUGR
- Priming donor MSCs before administration enhanced therapeutic efficacy for neuroprotection in this rat IUGR model
Written by the GCMD Library team from the infographic.
The infographic uses a teal and yellow color scheme with four main sections. The top shows the study model with test tube icons on the left and a flow diagram on the right. The middle section displays four experimental groups in white text boxes. The bottom contains results in white text and a yellow conclusion box. Institutional logos appear at the bottom.
New Infographic by Dr. Gigena Cecilia
"Brain protection by transamniotic stem cell therapy (TRASCET) in a model of intrauterine growth restriction (IUGR)"
Authors: Ashlyn E Whitlock, Kamila Moskowitzova, Daniel F Labuz, Ina Kycia, David Zurakowski, Dario O Fauza
Full article: https://www.jpedsurg.org/article/S0022-3468(22)00611-X/fulltext
Abstract
Purpose
Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown experimentally to reverse some of the effects of intrauterine growth restriction (IUGR), apparently by attenuating placental inflammation. Neurodevelopmental deficits driven by neuroinflammation are major complications of IUGR. We sought to determine whether MSC-based TRASCET also mitigates inflammation in the fetal brain.
Methods
Pregnant Sprague-Dawley dams (n = 8) were exposed to alternating 12-hour hypoxia (10.5% O2) cycles from gestational day 15 (E15) until term (E21). One group remained untreated (n = 28 fetuses). Three groups received volume-matched intra-amniotic injections into all fetuses (n = 72) of either saline (sham; n = 19), or a suspension of amniotic fluid-derived MSCs, either in native state (TRASCET; n = 20), or primed by exposure to interferon-gamma (IFN-γ) and interleukin-1beta (IL-1β) for 24 h prior to administration in vivo (TRASCET-Primed; n = 29). Donor MSCs were syngeneic Lewis rat cells phenotyped by flow cytometry. Normal fetuses served as controls (n = 20). Multiple analyses were performed at term, including ELISA in fetal brains for the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and IL-1β. Statistical comparisons were by Wilcox-rank sum test, including Bonferroni-adjusted significance.
Results
Overall survival was 75% (88/116). Gross brain weights were significantly decreased from normal in both the untreated and sham groups (both p<0.001) and significantly increased in both TRASCET groups when compared to untreated and sham (p = 0.003 to <0.001). TRASCET-Primed led to significantly lower levels of TNF-α and IL-1β compared to untreated (both p<0.001) and sham (p = 0.017 and p = 0.011, respectively). Non-primed TRASCET led to significantly lower levels of TNF-α and IL-1β compared to untreated (p = 0.009 to <0.001), but not sham (p = 0.133 and p = 0.973, respectively).
Conclusions
Transamniotic stem cell therapy with primed mesenchymal stem cells reverses some of the central nervous system effects of intrauterine growth restriction in a rat model, possibly by modulating neuroinflammation.