Imagine you could go back in time and become anything you wanted to be. Maybe you’d become a fireman, or an astronaut, or a doctor. Your options would be wide open. That’s what researchers have been able to do for certain cells in the body. They can coax cells back to a child-like state where they have the option to become any other cell in the body. These cells are called induced pluripotent stem cells, and they could be the key to curing diabetes and treating its complications.
Researchers at Joslin Diabetes Center are using induced pluripotent stem cells (or iPSCs for short) in all kinds of research.
“iPSCs are fabulous models for complex genetic diseases like diabetes,” says Amy Wagers, Ph.D., Investigator in the Section on Developmental and Stem Cell Biology and Core Director of the iPS Core Facility at Joslin Diabetes Center and Professor of Stem Cell and Regenerative Biology at Harvard University,. They are being used to study the development of complications and the progression of autoimmunity and insulin resistance. They are being turned into beta cells, muscle cells, brown fat. They are being used to study the effects of certain drugs on cells from people with diabetes. In short, they are allowing researchers to probe all aspects of a complicated disease.
iPSCs have the remarkable power to become anything in the human body. Unlike the more familiar (and controversial) embryonic stem cell, iPSCs start as any other normal cells in your body (though skin cells are the most easily accessible to doctors and therefore most commonly used). One day they get plucked from the surface of the body and brought into a lab. After some tinkering, they find themselves reverted back to what they were before they became skin cells, back to the early stem cell state. This process gives IPSCs the chance to do it all over again—they can become anything in the human body.
Being full of all these possibilities is known as “pluripotency.” This pluripotency is induced by processes in a lab. And so, we get induced pluripotent stem cells—iPSCs.
The scientific community used to believe that once a cell grew up (or differentiated, in scientific lingo), it sealed its fate; a skin cell couldn’t change its mind, go back to the stem cell state (or dedifferentiate) and suddenly become a cell of the heart, for example.
But in 2006 a Japanese scientist named Shinya Yamanaka figured out how to catalyze this reversion to a stem cell state in a lab, using certain proteins that reprogram the cell at a molecular level. Cells for iPSC creation can come from a skin biopsy or a blood sample. Then, researchers bathe their harvest in a solution full of those reprogramming proteins for about a month, until enough iPSCs emerge. Once in their stem cell state, researchers begin to push them forward again into whatever cells they need.
One promising area involves replacing damaged cells of different organs with refreshed cells made from the patient’s own body. Treatments using iPSCs would avoid transplant rejections, since the cells are already made up of the patient’s own DNA.
“We are looking at cell based therapy for many of the organs,” says George King, M.D., Chief Scientific Officer at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. Dr. King is working on treating problematic wound healing due to diabetic neuropathy using iPS cells.
Rohit Kulkarni, M.D., Ph.D., Senior Investigator in the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School,, is working on creating beta cells out of skin cells, which could then be transplanted back into the diabetic patients.
“[In regards to heart failure,] can you regenerate some of the heart muscles? [Or for brown fat,] can you actually stimulate brown fat progenitor cells and transplant brown fat and that could decrease obesity? There are people working on regenerating of the kidney, a certain part of the kidney that’s destroyed in diabetes, so that would be very important,” says Dr. King. “All these are potentially possible.”
The promise of these types of treatments is exciting, but could be far in the future. But iPSCs are delivering benefits to diabetes researchers already in the realm of understanding the progression of disease.
In the past, most diabetes research has been conducted in mice and other non-human organisms due to the problems inherent in studying humans on a cellular level. Mouse models have been helpful, but sometimes findings from mice don’t translate to humans. Now, with iPS cells, researchers have a model of human disease to work with. The can study the progression of the disease from the earliest cell state and pinpoint what goes wrong, and when.
“It’s a human model, and it’s a model where we can test [the functions of] specific candidate genes by either reducing their activity or turning them on,” says Mary Elizabeth Patti, M.D., Co-Director of the Joslin Advanced Genetics and Genomics Core and Director of the Hypoglycemia Clinic at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School. These human-models-in-a-culture-dish also allow researchers to target drugs to specific genes in the hopes of discovering new therapies. Dr. Patti and C. Ronald Kahn, M.D., Chief Academic Officer and Senior Investigator at Joslin Diabetes Center and the Mary K. Iacocca Professor of Medicine at Harvard Medical School, worked together to create the first human model of insulin resistance. They are using iPSCs to track metabolic changes throughout the differentiation of cells pulled from people with varying degrees of insulin resistance.
Dr. Kulkarni is also studying the progression of diabetes using iPSCs within the framework of a form of diabetes caused by a single gene mutation. He has also used iPSCs to study the development of complications within type 1 diabetes.
Dr. Wagers is working on new treatments for muscular dystrophy. She is using genetic modification (and a technique we’ll discuss here on the Speaking of Diabetes blog next week) within iPSCs to alter the more devastating form of muscular dystrophy into a variant of the disease that allows the patients to have longer, fuller lives.
“I want to emphasize the opportunity of using iPS cells because cell types such as those that make up the pancreas, liver, heart, eye, kidney or brain in living patients are not easily accessible for research,” said Dr. Kulkarni. “So one cannot go and take a small part of the heart cell or the nervous system, but the iPS cell allows us to derive these important cell types for investigation and make it a very unique resource which would otherwise not be possible.”