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Scientists Differentiate First of Kind iPS cells from Human Plexiform Neurofibroma to Neural Crest and Schwann Cells

Scientists Differentiate First of Kind iPS cells from Human Plexiform Neurofibroma to Neural Crest and Schwann Cells

A group of researchers from the Center for Regenerative Medicine in Barcelona (CMR[B]) and the Germans Trias i Pujol Research Institute (IGTP) in Badalona (Barcelona), Spain, in collaboration with researchers, reported on January 31 in Stem Cell Reports the first ever reprogramming of plexiform neurofibroma (pNF)-derived NF1 cells into induced pluripotent stem cells (iPSCs). These are the first iPSCs to be generated from a tumor predisposition syndrome-related benign tumor, and represent a non-perishable source of cells not generally available for slow growing tumors.

“Generating iPS cells directly from plexiform neurofibroma cells and differentiating them back to cells within the Schwann cell lineage resulted in a good strategy for obtaining a non-perishable cell-based model for these benign tumors. Now, neurofibromatosis researchers have access to a cell based system with the same genomic state as primary pNFs for drug screening and experiments requiring a fair amount of cells”, says Dr. Edu Serra, the primary investigator of the project.

Neurofibromas are tumors of the peripheral nerves that are found most commonly in people with neurofibromatosis type I (NF1), a neurogenetic disease with an estimated birth incidence of 1/2500-3000. A type of neurofibroma called a plexiform neurofibroma (pNF) affects up to 50% of people with NF1. These tumors can cause weakness, sensory changes, deformity, pain and of particularly notable concern, can convert to a deadly sarcoma called malignant peripheral nerve sheath tumor (MPNST).

Stem cells are cells early in their development before they have ‘been assigned’ a specific purpose (e.g. red blood cells to carry oxygen, white blood cells to fight infection). Treatment of human cells with specific gene-carrying vectors (e.g. retroviruses, Sendai virus) can reprogram the cells back into stem cells which can then be turned into (or differentiated into) all of the cell types in the human body. Fibroblasts from the skin are the typical source of cells used for reprogramming, but in this novel work cells composing pNFs were converted into pluripotent cells in order to maintain their genomic status. These iPSCs were then differentiated back into cells of the Schwann cell and neural crest lineage were shown to retain the genetic background and proliferation properties of the original pNF-forming Schwann cells. The versatile and high fidelity nature of those iPSCs enable biological studies and drug testing at different stages of cellular development, and so these cells represent a valuable tool towards improving our understanding of the relative contribution of each cell type to pNF tumorigenesis and the effects of a drug treatment at each step of disease development. This is of great importance to accelerate therapeutic discovery for the NF1 field as well as other Rasopathies.

The pNF-derived iPSCs produced by the team (named as 3PNF_FiPSsv_PM_2, 3PNF_SiPSsv_MM_11, 5PNF_TDiPSsv_MM_4, 5PNF_TDiPSsv_PM_6, 6PNF_SiPSrv_PM_2, and 7PNF_SiPSrv_PM_12) have been banked in the Barcelona node of the Spanish National Cell Bank (Banco Nacional de Lineas Celulares), located at CMR[B] facilities, and are now available to the international research community. In addition, genomic data generated for characterizing these cells with comparison to their primary donor pNF cells is openly available through the NF Data Portal managed by Sage Bionetworks (

This work was a major cell culture initiative of the Neurofibromatosis Therapeutic Acceleration Program (NTAP). The goals of the initiative were to explore the degree of genomic, molecular and cellular variation within pNF and create a non-perishable source of cells to model NF1 pathogenesis and be compatible with drug-screening analyses for the identification of new therapeutics for pNF.

Enllaços relacionats
Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas

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