Humanized Skeletal Muscle in Pig: Novel Model and Tissue Source for VML
Abstract
Objectives and Rational: Battlefield casualty and trauma often results in major injury to the extremities, one example of this is volumetric muscle loss (VML) injuries. While advances in prolonged field care have saved many Service members’ lives, those with VML injures are left with long-term functional complications. Unlike more simple muscle injuries, VML injuries are not capable of healing significantly, leading to permanent disability. VML is hard to study because animal models are limited. As a result, discovering new treatments is difficult. Currently, there is no way to transplant skeletal muscle into injuries. Herein, we propose the development of an unprecedented new animal model in pigs which have human muscles that we will use to test new therapies for VML. The humanized skeletal muscle may also one day be a source of skeletal muscle to treat injured Soldiers. Our objective will be reached in the proposed studies by engineering live pigs that lack native pig muscle and instead have human skeletal muscle. Achieving this objective will result in the development of two unprecedented products: (1) a humanized model of VML to test new treatments and eventually (2) an unlimited supply of human muscle to treat VML injuries. These products will greatly increase our chances of making significant advances in the treatment of VML. These products will address an unmet need for some of the most significantly wounded Service members evacuated from current conflicts. Research Applicability: The proposed work directly addresses the Fiscal Year 2018 Peer Reviewed Orthopaedic Research Program Applied Research Awards Focus Areas of (1) Animal Models and (2) Tissue Regeneration, which respectively represent the immediate and long-term benefits of this work. Approximately 14,500 Service members were evacuated from war between 2001 and 2013, and about 77% had some form of musculoskeletal injuries. Of injuries that limit Service members from returning to duty ~83% are orthopaedic, and many have VML injury. Extremity combat casualties cost the Department of Defense $42.4 billion in initial treatment costs. They contribute to a total lifetime cost of $108.8 billion in disability benefits to injured Service members and require long hospitalization and rehabilitation times. Using the Army Physical Evaluation Board, it has been shown that disability ratings following VML-related injuries do not improve over time, even when Soldiers are given additional time to recover and rehabilitate. Currently, there are no good treatment options for VML. Surgical reconstruction does little to improve skeletal muscle function and requires taking healthy tissues from other parts of the patient’s body. This work will have immediate and long-term impact on the care of Wounded Warriors and all patients with VML. In the near future, this work will result in an unprecedented model of human VML, which will allow novel exploration of bold therapies in the absence of human risk. We expect to have a working humanized animal model that can be used to test new treatments for VML within the funding period of this proposal. Depending on treatments tested (that others are currently developing), it is reasonable to expect that direct improvements in patient outcomes might be seen within 1 additional year. Once the model is established, work may also begin to use muscles from humanized pigs to treat patients with VML. Service Member Benefit: This proposal is expected to benefit injured Service members. This work addresses the most significant and devastating extremity injuries among military Service members evacuated from the battlefield. Development of both a humanized skeletal muscle model and tissue source for transplantation are expected to revolutionize clinical care and provide a necessary treatment option the can improve skeletal muscle function for those patients that undergo limb salvage. The long-term functional limitations of
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910610
Entities
People
- Mary G Garry
Organizations
- United States Army
- University of Minnesota