Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice

Abstract

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug treatment for ASD patients. Currently, stem cells, including human amniotic epithelial cell (hAEC) transplantation, seem to be a promising treatment for ASD, but the effectiveness needs to be verified, and the mechanism has not been clarified. Methods We intraventricularly transplanted hAECs into a 2-month-old BTBR T+tf/J (BTBR) mouse model of ASD. Behavior tests were detected 1 month later; hippocampal neurogenesis, neuroprogenitor cell (NPC) pool, and microglia activation were analyzed with immunohistochemistry and immunofluorescence; the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were determined by real-time PCR or western blotting. Results After intraventricular injection of hAECs into adult males, social deficits in BTBR mice were significantly ameliorated. In addition, hAEC transplantation restored the decline of neurogenesis and NPCs in the hippocampus of BTBR mice by expanding the stem cell pool, and the decreased levels of BDNF and TrkB were also rescued in the hippocampus of the hAEC-injected BTBR mice. Meanwhile, the transplantation of hAECs did not induce microglial overactivation or excessive production of pro-inflammatory cytokines in the hippocampus of BTBR mice. Conclusions Based on these results, we found that hAEC transplantation ameliorated social deficits and promoted hippocampal neurogenesis in BTBR mice. Our study indicates a promising therapeutic option that could be applied to ASD patients in the future.

Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

“…Autism spectrum disorder (ASD) is a complicated disorder in neural development involved in social connectivity and interaction [ 102 ]. Zhang et al observed that the intraventricular injection of hAESCs alleviated the social deficits by rescuing the function of hippocampus in BTBR mice [ 103 ]. Mucopolysaccharidosis type 1 (MPS1) is characterized by the dysfunction of lysosomal storage and is often accompanied by neurological degeneration [ 104 ] and hAESCs injection ameliorated the ability of sensorimotor coordination in MPS1 mice [ 105 ].…”

Immunomodulatory Properties of Amniotic Membrane Derivatives and Their Potential in Regenerative Medicine

“…The hAM has been studied since many years and is used in the treatment of burns, skin defects, and corneal injuries [15,16]. Because of their antiinflammatory and immunomodulatory properties, human amniotic cells have been considered as valid candidates for cell therapy in several degenerative disorders [17][18][19][20].…”

AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function

“…General exploratory locomotion in the open field apparatus was evaluated according to our previous described ( Zhang et al, 2019 ). During the test, a mouse was placed in the center of open field box and allowed to explore for 30 min.…”