Scientists at USC untangle the mysteries of cellular reprogramming- a method that could be used to treat diseases

Dr. Justin Ichida, Assistant Professor at USC and lead author of the study

Scientists have long tried to repurpose cells in order to potentially treat various types of conditions. This process, called reprogramming, involves changing one type of cell into another, such as a blood cell into a muscle cell or nerve cell. Although the technique has been around for decades, it has only been effective 1% of the time.

Fortunately, thanks in part to a CIRM grant, Dr. Justin Ichida and other researchers at USC have been able to untangle this complicated process to ensure reprogramming happens more efficiently. The researchers were able to figure out a process that reprograms cells much more reliably than previous methods.

USC scientists have found a solution to untangle twisty DNA, removing kinks so the molecules can be used to reprogram cells to advance regenerative medicine to treat disease.
Photo courtesy of Illustration/iStock

The technique the scientists developed uses an enzyme to untangle reprogramming DNA, similar to how a hairdresser conditions untangled hair. Since DNA molecules are twisty by nature, due to the double helix configuration, they do not respond well when manipulated to change itself. Therefore, reprogramming DNA requires uncoiling, yet when scientists begin to unravel the molecules, they knot up tighter.

“Think of it as a phone cord, which is coily to begin with, then gets more coils and knots when something is trying to harm it,” Dr. Ichida said in a press release by USC.

To smooth the kinks, the researchers treated cells with a chemical and genetic cocktail that activates enzymes that open up the DNA molecules. This process releases the coiled tension and lays out the DNA smoothly, leading to more efficient cellular reprogramming.

This new technique works almost 100% of the time and has been proven in human and mouse cells. The increased efficiency of this techniques opens the possibilities for studying disease development and drug treatments. New cells could be created to replace lost cells or acquire cells that can’t be extracted from people, a problem observed in Parkinson’s, ALS, and other neurological diseases.

Moreover, since these reprogrammed cells are the same age as the parent cell, they could be used to better understand age-related diseases. It is possible that the reprogrammed cells may be better at creating age-accurate models of human disease, which are useful to study a wide array of degenerative diseases and accelerated aging syndromes.

To summarize his work, Dr. Ichida states in the USC press release that,

“A modern approach for disease studies and regenerative medicine is to induce cells to switch their identity. This is called reprogramming, and it enables the attainment of inaccessible tissue types from diseased patients for examination, as well as the potential restoration of lost tissue. However, reprogramming is extremely inefficient, limiting its utility. In this study, we’ve identified the roadblock that prevents cells from switching their identity. It turns out to be tangles on the DNA within cells that form during the reprogramming process. By activating enzymes that untangle the DNA, we enable near 100% reprogramming efficiency.”

The full findings of this study can be found in Cell Stem Cell.

One thought on “Scientists at USC untangle the mysteries of cellular reprogramming- a method that could be used to treat diseases

  1. I’m seeking clinical trials or a clinic in (1)California, (2) Pennsylvania or (3)Florida.
    My son; Erick is an individual who had a severe disruption of the normal developmental process that occurred in the first 24 – 30 months of his life. This condition resulted in impaired language, cognitive, social and adaptive functioning which caused Erick to fall further and further behind his peers as he grew older. Prior to the disruption Erick was functioning at about 4 – 6-year level in all areas of development. Erick is now a young adult.
    Also, I would like some information on successful clinical trials with stem cell treatment/therapy individuals of all ages with autism.
    A case of an adult with autism (33 year old), administered with autologous BMMNCs twice at an interval of 6 months was also reported. Over a period of 9 months, his ISAA scores reduced from 94 (Mild autism with 60% disability) to 64 (no autism). The CGI showed improvement by change in severity of illness from 3 (mildly ill) to 1 (borderline mentally ill). Global improvement on CGI was scored 2 (much improved) with an efficacy index of 5 (moderate therapeutic effect). PET CT scan repeated at 6 months, showed a balancing effect in the metabolism of frontal, temporal, mesial temporal, amygdale, hippocampus, para hippocampus, parietal, para hippocampus, basal
    ganglia, cerebellum amongst others. Functionally, improvements were observed in his attention span, tongue movements, eye contact, eye-hand co-ordination, behavior pattern, language and communication, sensory aspects, problem solving. There was significant decrease in aggressive behavior and hyperactivity [58].

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