TY - JOUR
T1 - Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis
AU - Li, Bo
AU - Lee, Carol
AU - O’Connell, Joshua S.
AU - Antounians, Lina
AU - Ganji, Niloofar
AU - Alganabi, Mashriq
AU - Cadete, Marissa
AU - Nascimben, Francesca
AU - Koike, Yuhki
AU - Hock, Alison
AU - Botts, Steven R.
AU - Wu, Richard Y.
AU - Miyake, Hiromu
AU - Minich, Adam
AU - Maalouf, Michael F.
AU - Zani-Ruttenstock, Elke
AU - Chen, Yong
AU - Johnson-Henry, Kathene C.
AU - De Coppi, Paolo
AU - Eaton, Simon
AU - Maattanen, Pekka
AU - Delgado Olguin, Paul
AU - Zani, Augusto
AU - Sherman, Philip M.
AU - Pierro, Agostino
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment. Amniotic fluid stem cells (AFSC) and AFSC-derived extracellular vesicles (EV) can be used to improve intestinal injury in experimental NEC. However, the mechanisms by which they affect the Wnt/β-catenin pathway and intestinal regeneration are unknown. In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway. AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium. EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction. AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NEC.
AB - Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment. Amniotic fluid stem cells (AFSC) and AFSC-derived extracellular vesicles (EV) can be used to improve intestinal injury in experimental NEC. However, the mechanisms by which they affect the Wnt/β-catenin pathway and intestinal regeneration are unknown. In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway. AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium. EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction. AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NEC.
UR - https://www.scopus.com/pages/publications/85090965770
U2 - 10.1038/s41419-020-02964-2
DO - 10.1038/s41419-020-02964-2
M3 - Article
C2 - 32929076
AN - SCOPUS:85090965770
SN - 2041-4889
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 9
M1 - 750
ER -