Induced pluripotent stem cells have been generated for the first time from tumor cells in order to study therapies for tumors developed in patients with hereditary diseases with predisposition to cancer

The Hereditary Cancer Research Group at the Germans Trias i Pujol Research Institute (IGTP) on the Can Ruti Campus, Badalona has for the first time generated induced pluripotent stem cells (iPSCs) from tumors from people with the hereditary disease Neurofibromatosis type 1 (NF1). The work has been carried out in conjunction with Angel Raya of the Centre for Regenerative Medicine of Barcelona (CMRB) and published in Stem Cell Reports, the official journal for the International Society for Stem Cell Research (ISSCR).

iPSCs are stem cells capable of giving rise to most other types of cell in the body. It is quite normal to generate stem cells by reprogramming skin cells extracted from patients with hereditary diseases such as NF1 to study them as a model for the disease, but the IGTP researchers have now generated iPSCs for the first time as a valid model for NF1 from cells from tumors. Instead of using skin cells, we have reprogrammed cells from tumors from patients with NF1 in order to have a model of cells genetically identical to the tumor cells, explains Eduard Serra, leader of the work at the IGTP.

One of the difficulties of studying these pathologies with cells obtained directly from benign tumors is that they are finite, but now we have achieved a cellular model which will not run out because, due to their characteristics, we can culture these iPSCs indefinitely and then convert them into the same cells that make up a tumor, Serra adds. The work has invested most of the efforts in converting these iPSCs into Schwann cells, which are cells which make up plexiform neurofibromas, typical of NF1. The resulting cells have the same capacity to proliferate as the original tumor cells. As iPSCs are an endless source of cells, we have been able to generate the resource we needed. Now we can test drugs that inhibit proliferation, study the mechanisms by which these tumors develop and try to stop them developing into malignant tumors, explains Meritxell Carri, first author of the article.

New ways to study NF1

The Hereditary Cancer Research Group at the IGTP has been studying Neurofibromatoses for many years, this includes NF1, a minority disease that affects 1 in every 3,000 people in the world. It is a hereditary disease, which brings a high predisposition to develop tumors in the peripheral nervous system. One of these types of tumor is the plexiform neurofibromas. It is a tumor that appears at birth, or in the first years of life, and forms on major nerves in the body, disorganizing and thickening the tissue surrounding the nerve and forming a tumor mass that can reach great dimensions. These tumors can impede functionality and disfigure the part of the body where they appear, which can be on the extremities or even on the face. Additionally, there is a risk that these tumors progress to become malignant; a sarcoma of the peripheral nerve sheath.

Although they start as benign tumors, we do not have drugs to put the patient into remission. To develop effective drugs for this type of tumor we need cellular models that are faithful copies of the tumor and that do not run out, this is the model that now has been achieved.

Available to the scientific community

The cell lines generated have been deposited in the Carlos III Stem Cell Bank at the node kept at the CMRB in Barcelona. They are available to other researchers in the world who want to study this disease and these tumors.

This work was led by Eduard Serra at the IGTP and carried out in collaboration with Angel Raya at the CMRB alongside other participating institutions such as the Catalan Institute of Oncology (ICO), Sage Bionetworks, and the Germans Trias Hospital. This project has been financed by the Neurofibromatosis Therapuetic Acceleration Program (NTAP, http://www.n-tap.org), a program based at the Johns Hopkins University School of Medicine in Baltimore, Maryland in the United States, whose mission is to accelerate the development of therapies for Neurofibromatosis Type 1. The team has also had the support of the Spanish and Catalan Associations of Neurofibromatosis Patients.

The Johns Hopkins University, and the Germans Trias i Pujol Research Institute (IGTP) (http://www.germanstrias.org/) are academic institutions based respectively in Baltimore, Maryland, and Badalona (Barcelona), Spain.

The Center of Regenerative Medicine in Barcelona (CMR[B]) (www.cmrb.eu) is a public research centre (non-profit foundation) based in Barcelona, Spain. The overall mission of the CMR[B] is to conduct fundamental research of excellence forthe advancement inthe clinical translation of regenerative medicine strategies basedin pluripotent stem cells, mainly in the context of heart failure, neurodegenerative diseases, non-malignant hematological diseases and age-related macular degeneration.

Sage Bionetworks is a nonprofitbiomedical research and technology organization. We develop and apply open practices to data-driven research for the advancement of human health. Our interdisciplinary team of scientists and engineers work together to provide researchers access to technology tools and scientific approaches to share data, benchmark methods, and explore collective insights, all backed by Sages gold-standard governance protocols and commitment to user-centered design.Sage, founded in Seattle in 2009, is supported through a portfolio of competitive research grants, commercial partnerships, and philanthropic contributions. Learn more atwww.sagebionetworks.org.

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