These findings are particularly important given growing controversy in the scientific literature about whether subtle differences between iPSCs and ESCs should dampen enthusiasm for iPSCs to serve as an alternative source of differentiated precursor cells for various tissues, such as the liver, lung or blood. The new work provides compelling evidence that iPSCs have potential in regenerative medicine as an investigational tool for the development of treatments against diseases that affect endodermal-derived organs, such as cirrhosis, diabetes, cystic fibrosis and emphysema.
Darrell Kotton, MD, an associate professor of medicine and pathology at Boston University School of Medicine(BUSM), served as principal investigator and senior author for this study, which is published online in the Journal of Clinical Investigation (JCI). Constantina Christodoulou, BS, from BUSM’s program in genetics and genomics, was the lead author of the study.
iPSCs, discovered in 2006, are derived by reprogramming adult cells into a primitive stem cell state. They are similar to ESCs in terms of their ability to differentiate into different types of cells in vivo, including endoderm cells that give rise to liver and lung tissue. iPSCs do not require embryos and they are genetically identical to the patient’s cells, suggesting their future potential to be transplanted back into the same patient without risk of rejection. Additionally, iPSCs could reduce the reliance on ESCs, which remain highly controversial and have limited availability due to federal regulation.
Recently, however, there has been debate regarding whether the molecular differences found in iPSCs make them as functional for research as ESCs when used in regenerative medicine research.
Kotton and his colleagues set out to understand the limits and potential of iPSCs and whether they should be utilized in research as a basis for the development of potential therapies. They focused their research on the capacity of iPSCs to undergo differentiation in vitro into endodermal tissue.
Working together with the laboratory of Gustavo Mostoslavsky, MD, PhD, assistant professor of medicine at BUSM, the teams of CReM investigators generated their own iPSC lines by reprogramming skin fibroblasts using a special stem cell cassette vector (STEMCC). They interrogated the global gene expression profiles of each cell line during endodermal differentiation and also compared the resulting cells to authentic endoderm from early developing mouse embryos.
“We found that although there are subtle molecular differences between iPSCs and ESCs, their functional potential to differentiate was virtually indistinguishable in vitro,” said Kotton, who is a co-director of CReM. “It is important to understand that iPSCs offer many possibilities in regenerative medicine and developmental biology research and may hold the key to future medical treatments for many human diseases.”
The next step, said Kotton, is to further differentiate iPSCs into more specific cell types using both mouse and human stem cell lines. CReM currently has 100 stem cell lines from donors with lung-specific diseases that will be used in the research to develop potential treatments against diseases that affect the lungs.
The CReM-led research was done in collaboration with other researchers at BU, including the laboratory of Avi Spira, MD, chief of computational biomedicine at BUSM, the laboratory of Paul Gadue, PhD, at the University of Pennsylvania and the laboratory of Valerie Gouon-Evans, PhD, at Mount Sinai School of Medicine.
Jenny Eriksen | EurekAlert!
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences