Hereditary Cancer Group, Germans Trias i Pujol Research Institute (IGTP)-PMPPC-CIBERONC, Can Ruti Campus, Badalona, Barcelona 08916, Spain.
Center of Regenerative Medicine in Barcelona (CMRB), Hospitalet de Llobregat, Barcelona 08098, Spain; Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Hospitalet de Llobregat, Barcelona 08098, Spain.
Stem Cell Reports. 2019 Feb 12;12(2):411-426. doi: 10.1016/j.stemcr.2019.01.001. Epub 2019 Jan 31.
Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disease caused by mutations in the NF1 tumor suppressor gene. Plexiform neurofibromas (PNFs) are benign Schwann cell (SC) tumors of the peripheral nerve sheath that develop through NF1 inactivation and can progress toward a malignant soft tissue sarcoma. There is a lack of non-perishable model systems to investigate PNF development. We reprogrammed PNF-derived NF1(-/-) cells, descendants from the tumor originating cell. These NF1(-/-)-induced pluripotent stem cells (iPSCs) captured the genomic status of PNFs and were able to differentiate toward neural crest stem cells and further to SCs. iPSC-derived NF1(-/-) SCs exhibited a continuous high proliferation rate, poor myelination ability, and a tendency to form 3D spheres that expressed the same markers as their PNF-derived primary SC counterparts. They represent a valuable model to study and treat PNFs. PNF-derived iPSC lines were banked for making them available.
神经纤维瘤病 1 型（NF1）是一种由 NF1 肿瘤抑制基因突变引起的肿瘤易感性遗传疾病。丛状神经纤维瘤（PNFs）是周围神经鞘的良性雪旺氏细胞（SC）肿瘤，通过 NF1 失活发展而来，并可能向恶性软组织肉瘤进展。目前缺乏可用于研究 PNF 发展的非易腐模型系统。我们对源自肿瘤起始细胞的 PNF 衍生 NF1(-/-)细胞进行了重编程。这些 NF1(-/-)诱导多能干细胞（iPSC）捕获了 PNF 的基因组状态，并能够向神经嵴干细胞分化，并进一步分化为 SC。iPSC 衍生的 NF1(-/-)SCs 表现出持续的高增殖率、较差的髓鞘形成能力以及形成 3D 球体的趋势，这些球体表达与其 PNF 衍生的原发性 SC 对应物相同的标记物。它们代表了研究和治疗 PNF 的有价值的模型。已经储存了 PNF 衍生的 iPSC 系，以备将来使用。
