Understanding and Tuning Macrophage Phenotype in Volumetric Muscle Loss (VML) Injury
Wednesday, May 1, 2024
1:00 PM-3:00 PM
BIOMED PhD Thesis Defense
Title:
Understanding and Tuning Macrophage Phenotype in Volumetric Muscle Loss (VML) Injury
Speaker:
Ricardo Checchia Whitaker, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Kara Spiller, PhD
URBN Professor of Biomedical Innovation
School of Biomedical Engineering, Science and Health Systems
Drexel University
Details:
Volumetric Muscle Loss (VML) is defined as the sudden loss of 20% or more of muscle mass, leading to tissue impairment. The current standard of care, consisting of rehabilitation, surgery, or amputation, is clearly ineffective. The sole therapy in clinical trials attempts to promote tissue regeneration via implantation of a decellularized matrix scaffold, nonetheless this approach also falls short of entirely reestablishing tissue function. The existing gap in knowledge behind the underpinning mechanisms driving VML pathology hinders the development of better therapeutics.
Recent studies uncovered the presence of dysfunctional macrophages following critical size VML injuries. Macrophages have been shown in vitro and in other models of muscle repair to be crucial for muscle regeneration due to its vital influence on supporting cells, such as stem cells, endothelial cells, and fibroblasts. Nonetheless, the mechanism(s) driving macrophages dysfunction following VML remain elusive. The goals of this thesis are to establish these mechanisms driving immune dysregulation, particularly on macrophages following VML, and make strides on the development of better therapeutics.
In this work, we have established a full timeline of macrophage dysfunction, both in the protein and gene level, from injury onset to the establishment of fibrosis. Next, we have uncovered previously unknown systemic changes in immune response, such as immune cell presence in the bone marrow, changes in splenic macrophage phenotype and blood serum cytokine levels, derived from this localized injury. In addition, we identified neutrophils as potential mediator of macrophage dysfunction. Lastly, we identified potential drugs and biomaterials to leverage a novel macrophage cell therapy approach for the treatment of VML.
The results from this thesis deepen our knowledge on some of the previously unknown mechanisms driving immune dysfunction and therefore tissue impairment after VML. It also lays down groundbreaking advances in possible treatments for VML patients.
Contact Information
Natalia Broz
njb33@drexel.edu