Have you ever seen your nieces or nephews or a high school friend after a ten year hiatus? You are amazed at how much they have changed. You wonder when did they grow up? It seemingly happened overnight and that is slightly disconcerting.
Time and absence can play that trick on science too. In April 2008, I reported in these “pages” on the Stem cell frontier on display at Promega. In that conference, UW Scientist, Jamie Thomson, gave an update on his recent discovery on how to turn fully differentiated, mature cells into new stem cells that could, via biological magic, turn into any different mature tissue cell type. These he called induced pluripotent stem cells or iPSs. Thomson accomplished this breakthrough using inefficient gene transfer technology that was not easily available to all scientists. And, at that time, it was unclear how to control the process by which the iPSs morphed into the various mature cell types. Yet, it was heralded as an important advance that could remove ethical concerns around destroying human embryos in order to obtain stem cells to use for research and health.
Fast forward to April 19, 2017 and the Engineering Cells and Tissues for Discovery and Therapy symposium at the Promega BioPharmaceutical Technology Center in Fitchburg where it was clear that the iPS child is now a young adult.
The conference featured vendors marketing their special tissue culture media that could coax adult cells “back to the future” as stem cells and other commercial media could drive them to become specific adult cell types. This makes the technology available to anyone with a cell incubator and sterile tissue culture hood (i.e., any cell biology laboratory). If you wanted to, you could make stem cells in your garage as folks are doing with DIY biology. It now is not much more difficult to make stem cells than making a good chili from a recipe. Also, the speakers at the conference almost flippantly talked about human iPSs as if they were as common as common a tool as a screw driver—everyone has one. They talked about turning iPS cells into various adult cell types such as specialized heart cells from different regions of the organ, cells from the gut, stomach and esophagus, retinal cells and cells that can reform the blood-brain barrier in tissue culture. They also described making new immune cells that specifically target molecules on the surface of some types of cancers, and they talked about making vascular smooth muscle cells that stretch and resist pressure just as artery cells do when blood is pushed through them. It was a “wow” moment. When did all this happen?
In fact, the field has matured even beyond being able to easily make stem cells and have them do your bidding to become specific tissue types. Speaker Christine Mummery, PhD, Chair of Anatomy and Embryology, Leiden University Medical Center, The Netherlands, expressed this as “disease models in a dish.” Toward this end, stem cell derived adult cells have become very useful for screening the efficacy and toxicity of new drugs and even for finding new uses for existing drugs. For example, another speaker briefly talked about testing an already existing drug for its ability to also treat amyotrophic lateral sclerosis or ALS (Lou Gherig’s Disease).
James Wells, PhD, Director of the Pluripotent Stem Cell Center at the University of Cincinnati Medical School, described research using iPS cells to develop three-dimensional tissues from different regions of the gut, stomach and esophagus. These organoids contained the different cells types associated with these tissues, including functional nerve and smooth muscle cells that rendered them capable of peristaltic-type motility. His lab is using these tissues to investigate the response of gut organoids to Helicobacter pylori, the pathogen associated with gastric ulcers, and to model genetic forms of digestive diseases.
At the other end of the body, Eric Shusta, PhD, Howard Curler Distinguished Professor, Department of Chemical and Biological engineering at the University of Wisconsin-Madison described how iPS cells could be used to recreate the blood brain barrier (BBB) in tissue culture. These barriers grown in tissue culture are used to examine how diseases affect the brain and for testing drugs for BBB permeability. This has important implications for treating Alzheimer’s and Parkinson’s diseases as well as brain cancer.
Finally, Krishanu Saha, PhD, from UW-Madison and Michael Sadelain, MD, PhD, Memorial Sloan Kettering Cancer Center used new CRISPR-Cas9 “gene editing” tools to correct genomic problems and to insert genes encoding new chimeric antigen receptors (CAR) into stem cells that were coaxed into becoming T lymphocyte immune cells. This potentially provides investigators with renewable sources of engineered anti-cancer immune cells. Clinical trials to treat B cell lymphoma are underway at Sloan Kettering using these engineered stem-cell-derived immune cells and have shown very good preliminary results.
Yet, these advances, especially the work with gene editing in stem cells, raise new ethical concerns that need to be considered. Being able to modify the genomes of humans and animals raises a new class of ethical questions around the use of stem cells. It might be fine to use gene editing to replace diseased cells in a human, but would it be ok to engineer a human genome in a way that can be passed along to future generations?
A few years from now, I predict that there will be another stem cell conference that will represent an aged nephew of today’s stem cell science. It will talk about using organs developed in the laboratory for in vitro testing of new therapies. It will talk about early experiments on transplanting a functional pancreas into a diabetic patient or even a laboratory grown human heart into a patient.
This is when stem cell science will be mature. Kids and science sure grow up fast.
Steven S. Clark, Ph.D., is a former professor and medical researcher at the University of Wisconsin School of Medicine and Public Health. More recently he directed research development at the Milwaukee Institute for Drug Discovery and consults for universities, biotechnology companies and healthcare organizations. His blog BioScience Biz can be read at http://stevensclark.typepad.com/bioscience_biz
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