Activating Fetal Regeneration in Adult Tissue
Abstract
Topic Area: Tissue Regeneration (treatment for volumetric muscle loss [VML] and regeneration of neuromuscular junction [NMJ]). Central Problem: In recent years, advanced body armor, battlefield medicine, evacuation, and protective equipment have resulted in better survival rates than at any time in the history. But there is a flipside to the statistics. Many young wounded Soldiers are now returning home with life-changing disabilities such as scars. In addition to cutaneous scar, massive skeletal muscle loss sustained during battlefield injuries results in scar tissue formation. According to the Department of Veterans Affairs’ Annual Benefits Report for Fiscal Year 2016, there are approximately 4.4 million disabled Veterans with over 21 million disabilities. Of all the battlefield-associate extremity injuries, 53% of extremity injuries are penetrating soft-tissue wounds of various etiology such as strain, crush, and blast trauma. The primary factor that leads to partial disability in soft-tissue wounds is VML. VML is a major cause of Service-disqualifying disability in Service members. Bulk loss of muscle tissue (>20% by mass) in battlefield is often associated with damage to NMJ. In the aftermath of injury, NMJ regenerate very slowly and often suffer some months without function, leading to further muscle deterioration. Poor regeneration of the NMJ impairs functionality of the affected skeletal muscle. Additionally, traumatic scars affect patients physically, psychologically, and socially, leading to depression or anxiety, thereby affecting the quality of life. Innovation: The primary strength of this proposal is the notion that we have identified a molecular switch that, when activated, turns on highly efficient pathway of tissue regeneration that are characteristics of fetal tissue and typically not seen in adult tissue. The innovation of this proposal is in the discovery of the fetal mechanism by which such efficient regenerative potential can be engaged in the context of adult tissue healing. This pathway works across multiple organ system, making this lucrative for further development as a therapeutic intervention. Ultimate Applicability and Impact of Research: The observation that molecular switch proposed works across multi-organ system broadens the applicability of the proposed research. Success of the proposed project will provide a new strategy to recover neuromuscular function in those affected with significant loss of muscle during trauma. The same principle can be applied to achieve scar minimizing of the skin following burn. Successful completion of this project has the potential to contribute significantly to both basic and translational research involving tissue regeneration. From a basic research standpoint, this project will establish the pathway by which tissue regeneration can be achieved in adult conditions. This will also highlight potential roadblocks that need to be overcome to achieve successful tissue regeneration. At the translational research level, the project will also identify key molecules for pharmacological intervention for successful regeneration of NMJ.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010251
Entities
People
- Chandan K. Sen
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army