Engineering a New Approach to Cartilage Repair

Engineering a New Approach to Cartilage Repair

Genetic reprogramming of OA chondrocytes to improve cartilage repair

Dr. Rhima Coleman is an Assistant Professor of Biomedical and Mechanical Engineering at the University of Michigan. Dr. Coleman’s research interests focus on two areas of manipulating cell behavior in order to regenerate cartilage tissue, namely genetic reprogramming of cells and cell-matrix interactions. Dr. Coleman received her Bachelor’s degree in Mechanical Engineering from the University of Rochester, followed by a Master’s in the same field and a PhD in Bioengineering from the Georgia Institute of Technology. Dr. Coleman then undertook a postdoctoral position at the Hospital for Special Surgery in New York City, where she investigated methods to prevent mineralization of cartilage. In 2012, Dr. Coleman joined the University of Michigan to form the Cartilage Healing and Regeneration Laboratory. Here, she strives to develop mechanically functional cartilage replacement, allowing the restoration of joint mechanics to physiologically normal levels.

In Your Genes

Dr. Coleman uses her unique background to approach arthritis research in a novel and thought-provoking manner, combining elements of engineering and medical sciences. She is focused on genetic reprogramming of early osteoarthritic cartilage cells as a way in which to increase their ability to repair any defects that lead to cartilage damage.

To achieve this, Dr. Coleman uses an adaptation of a relatively new state of the art technique known as autologous chondrocyte implantation (ACI). Chondrocytes are the cells in our bodies that are responsible for cartilage production. ACI is a two-stage operative procedure: Firstly, a small piece of cartilage is surgically removed from a patient. This is then sent to a laboratory where it is treated with enzymes in order to isolate chondrocytes. These are then grown and expand greatly in number. Around 6-8 weeks after the first procedure, these cells will be returned to the surgeon to be implanted back in to the patient. These graft procedures have proven to be very successful when the initial harvest is taken from healthy cartilage cells. Unfortunately, this success is decreased in patients who exhibit early symptoms of osteoarthritis, patients whom are often those with the greatest need for such intervention.

In an effort to improve how this technique could be used in situations with higher risk patients, Dr. Coleman is seeking to genetically re-program these faulty chondrocytes. This is achieved by inserting a gene circuit into the cells, before implantation, thereby improving the level of repair and success achieved (measured by increased cartilage tissue production) using ACI in patients that display signs of early osteoarthritis. By creating sound repair options before such cells are implanted back into the patient, Dr. Coleman is hopeful that this will slow their progression to late-stage osteoarthritis.

Not an Impossible Dream

Working on various aspects of cartilage tissue engineering throughout her career has been the mark of Dr. Coleman. As she progressed through her training, she came to the realization that techniques were necessary to control how a cell responds to the volatile environment created when a joint injury occurs. In order to achieve this, Dr. Coleman took the approach of working from the inside out – seeking to directly suppress the activity of factors inside the cell that caused cartilage degeneration. Many of the colleagues she approached who were working in the field of molecular biology thought this was a “pie in the sky” approach and would be extremely difficult to achieve in mammalian cells. Dr. Coleman was not deterred. Through hard work and persistence, her team has made incredible strides in this field, creating a cutting-edge technology that could help millions of patients suffering from arthritis related joint injuries. The ANRF grant was instrumental in validating Dr. Coleman’s decision to pursue a course of research considered high risk, but as she has demonstrated, with high risk comes the possibility of high reward. Furthermore, the creation of the gene circuit has led to an environment in which the trainees and post-doctoral researchers in the laboratory are highly motivated and enthusiastic, building on the momentum created by this research.

Where to from Here?

Dr. Coleman will continue to evaluate how modifications to the gene circuit will influence various populations of chondrocytes and stem cells for applications relating to cartilage tissue engineering. The influence on the gene circuits by cues from the environment in which the cells find themselves will also be addressed, with the ultimate goal to fine tune these gene circuits for optimal functioning and repair in the various physiological settings. This holds the potential to vastly improve the level of repair that patients with osteoarthritic injuries can expect, helping to achieve reduced pain and improved mobility.

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Article Author
Arthritis National Research Foundation

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. There are several ways to support research through the ANRF. Find out more and donate today.

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