Lyophilized Extracellular Vesicles from Adipose-Derived Stem Cells Increase Muscle Reperfusion but Degrade Muscle Structural Proteins in a Mouse Model of Hindlimb Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury is a complication impacting multiple organs and tissues in clinical conditions ranging from peripheral arterial disease to musculoskeletal trauma and myocardial infarction. Stem cell-derived extracellular vesicles (EVs) may represent one therapeutic resource for preventing the tissue damage associated with I/R injury. Here we tested the hypothesis that lyophilized extracellular vesicles derived from adipose stem cells could serve as an "off-the-shelf" treatment modality for I/R injury in a mouse hindlimb ischemia model.

Hindlimb Immobilization Increases IL-1β and Cdkn2a Expression in Skeletal Muscle Fibro-Adipogenic Progenitor Cells: A Link Between Senescence and Muscle Disuse Atrophy.

Loss of muscle mass and strength contributes to decreased independence and an increased risk for morbidity and mortality. A better understanding of the cellular and molecular mechanisms underlying muscle atrophy therefore has significant clinical and therapeutic implications. Fibro-adipogenic progenitors (FAPs) are a skeletal muscle resident stem cell population that have recently been shown to play vital roles in muscle regeneration and muscle hypertrophy; however, the role that these cells play in muscle disuse atrophy is not well understood.

The cyclophilin inhibitor NIM-811 increases muscle cell survival with hypoxia in vitro and improves gait performance following ischemia-reperfusion in vivo.

Acute ischemia-reperfusion injury in skeletal muscle is a significant clinical concern in the trauma setting. The mitochondrial permeability transition inhibitor NIM-811 has previously been shown to reduce ischemic injury in the liver and kidney. The effects of this treatment on skeletal muscle are, however, not well understood.

Targeting the Mitochondrial Permeability Transition Pore to Prevent Age-Associated Cell Damage and Neurodegeneration.

The aging process is associated with significant alterations in mitochondrial function. These changes in mitochondrial function are thought to involve increased production of reactive oxygen species (ROS), which over time contribute to cell death, senescence, tissue degeneration, and impaired tissue repair. The mitochondrial permeability transition pore (mPTP) is likely to play a critical role in these processes, as increased ROS activates mPTP opening, which further increases ROS production.

Therapeutic application of extracellular vesicles for musculoskeletal repair & regeneration.

Traumatic musculoskeletal injuries are common in both the civilian and combat care settings. Significant barriers exist to repairing these injuries including fracture nonunion, muscle fibrosis, re-innervation, and compartment syndrome, as well as infection and inflammation. Recently, extracellular vesicles (EVs), including exosomes and microvesicles, have attracted attention in the field of musculoskeletal regeneration.

Freeze-Dried Extracellular Vesicles From Adipose-Derived Stem Cells Prevent Hypoxia-Induced Muscle Cell Injury.

Cellular therapies have tremendous potential for the successful treatment of major extremity wounds in the combat setting, however, the challenges associated with transplanting stem cells in the prolonged field care (PFC) environment are a critical barrier to progress in treating such injuries. These challenges include not only production and storage but also transport and handling issues. Our goal is to develop a new strategy utilizing extracellular vesicles (EVs) secreted by stem cells that can resolve many of these issues and prevent ischemic tissue injury.