Kristina Bernardi, Jun Luo, Matthew Weaver, Robert Welikson
Dr. Margaret Allen's tissue engineering research is focused upon the active repair of muscle. This includes repair of heart muscle following myocardial infarction (heart attack) to prevent heart failure, and repair and reconstruction of skeletal muscle after trauma or injury. Projects include:
Inflammation and Cardiac Repair: After a heart attack, cardiac tissue goes through an immune response that orchestrates the removal of damaged tissue and the initiation of repair. If the removal phase, the inflammatory phase, is too robust the wall of the heart becomes very thin and is susceptible to rupture. If the repair phase is too modest, insufficient repair tissue is formed. The Allen Laboratory is working on methods to direct this immune response to decrease the inflammatory phase while preserving the repair phase. Using Glucan Encapsulated RNA-loaded Particles (GeRPs), the Allen laboratory can directly modulate the macrophages that invade cardiac tissue immediately post-myocardial infarct. GeRPs loaded with interfering RNA to the molecule MAP4K are injected into infarcted hearts and the GeRPs are ingested by infiltrating macrophages which then inhibits their inflammatory response without harming their ability to initiate repair. The goal is to develop a treatment for patients having experienced a heart attack to improve their natural repair, thus improving heart function and longevity.
Fixing Broken Hearts: After a heart attack, the wall of the heart often thins and loses its ability to pump blood efficiently. The Allen Laboratory is investigating the use of natural cardiac patches from the atrial appendage to patch those thinned regions of the heart. To improve the viability of the transplanted patches, a cytoprotective agent, cobalt protoporphyrin, is used to enhance the survival of the patch tissue and promote repair. Recent results have shown increased survival of patches treated with cobalt protoporphyrin and increased heart function in hearts receiving a patch. The long-term goal is to develop a treatment for patients who have experienced a major myocardial infarction.
Limb Reconstruction: After severe traumatic injuries, there is often insufficient muscle tissue available to retain limb function. As a means to reconstruct limbs, the Allen laboratory is developing methods to fabricate skeletal muscle constructs from a patient’s own cells that can be used to rebuild muscle tissue. The cytoprotective agent cobalt protoporphyin is used to increase the survival of these implanted muscle constructs and thus promote repair. The goal of these studies is to develop methods to efficiently extract and grow a patient’s own cells, and use those cells to fabricate implantable repair muscle tissue.
Cross-section of skeletal muscle showing muscle fibers (green) and a nerve (red). Cell nuclei are stained blue.
The Allen Laboratory
Margaret Allen, MD, FACS, Dr. Sc. (Hon.)
Jun Luo, MD
Robert Welikson, PhD
Matthew Weaver, PhD