Molecular signature of amniotic fluid derived stem cells in the fetal sheep model of myelomeningocele

详细信息    查看全文

• 作者：Gabriele Ceccarelli^a ; ¹ ; Enrico Pozzo^a ; ^b ; ¹ ; Federico Scorletti^c ; ¹ ; Laura Benedetti^a ; Gabriella Cusella^a ; Flavio Lorenzo Ronzoni^d ; Vardine Sahakyan^b ; Elisa Zambaiti^c ; Maria Chiara Mimmi^e ; Valeria Calcaterra^f ; Jan Deprest^g ; Maurilio Sampaolesi^a ; ^b ; ^{sampa@unipv.it" class="auth_mail" title="E-mail the corresponding author} ; Gloria Pelizzo^c
• 关键词：Myelomeningocele ; Amniotic fluid derived stem cells ; Sheep model ; Gene signature
• 刊名：Journal of Pediatric Surgery
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：50
• 期：9
• 页码：1521-1527
• 全文大小：957 K

文摘

Abnormal cord development results in spinal cord damage responsible for myelomeningocele (MMC). Amniotic fluid-derived stem cells (AFSCs) have emerged as a potential candidate for applications in regenerative medicine. However, their differentiation potential is largely unknown as well as the molecular signaling orchestrating the accurate spinal cord development. Fetal lambs underwent surgical creation of neural tube defect and its subsequent repair. AFSCs were isolated, cultured and characterized at the 12th (induction of MMC), 16th (repair of malformation), and 20th week of gestation (delivery). After performing open hysterectomy, AF collections on fetuses with sham procedures at the same time points as the MMC creation group have been used as controls. Cytological analyses with the colony forming unit assay, XTT and alkaline-phosphatase staining, qRT-PCR gene expression analyses (normalized with aged match controls) and NMR metabolomics profiling were performed. Here we show for the first time the metabolomics and molecular signature variation in AFSCs isolated in the sheep model of MMC, which may be used as diagnostic tools for the in utero identification of the neural tube damage. Intriguingly, PAX3 gene involved in the murine model for spina bifida is modulated in AFSCs reaching the peak of expression at 16 weeks of gestation, 4 weeks after the intervention. Our data strongly suggest that AFSCs reorganize their differentiation commitment in order to generate PAX3-expressing progenitors to counteract the MMC induced in the sheep model. The gene expression signature of AFSCs highlights the plasticity of these cells reflecting possible alterations of embryonic development.