Browsing by Subject "Muscle regeneration"

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SDF-1/IGF-1 conjugated to a PEGylated fibrin matrix as a treatment for an ischemia reperfusion injury in skeletal muscle repair
(2012-12) Pham, Chantal Bich Phuong; Farrar, Roger P.; Suggs, Laura J
Ischemia/reperfusion (I/R) injury causes extensive damage to skeletal muscle, often resulting in prolonged functional deficits. This current study determines the efficacy of controlled release of SDF-1α and IGF-1 by conjugation to biodegradable, polyethylene glycol, (PEG)ylated fibrin gel matrix in skeletal muscle repair of an I/R injury. Male Sprague-Dawley rats underwent a 2-hour tourniquet induced I/R injury on their hind limbs. Twenty-four hours post injury the following treatments were administered: PEGylated fibrin gel (PEG-Fib), SDF-1 conjugated PEGylated fibrin gel (PEG-Fib/SDF-1), or dual protein IGF-1 and SDF-1 conjugated PEGylated fibrin gel (PEG-Fibrin/SDF-1/IGF-1. Following 14 days after injury, functional and histological evaluations were performed. There was no significant difference in maximum tetanic force production recovery between PEG-Fib and PEG-Fib/SDF-1 groups. However, PEG-Fib/SDF-1/IGF-1 group resulted in significant improvement of force production relative to the other treatment groups. The same results were found for specific tension. Histological analysis revealed a greater distribution of small myofibers in the PEG-Fib/SDF-1 group than the PEG-Fib group, while the PEG-Fib/SDF-1/IGF-1 group had the smallest distribution of small fibers and similar to controls (uninjured). There were also a greater number of centrally located nuclei in the PEG-Fib/SDF-1 group than the PEG-Fib group, while the PEG-Fib/SDF-1/IGF-1 group had similar values to controls. Although these results confirm the protective role of exogenous IGF-1, SDF-1 did not have an effect on skeletal muscle repair.
The immunoregulation of dying cell components on macrophages and their therapeutic potential in ischemic muscle regeneration
(2021-11-29) Huang, Wenbai; Suggs, Laura J.; Farrar, Roger P.; Stone, Audrey; Zoldan, Janet; Ehrlich, Lauren
Skeletal muscle regeneration after serious injury highly relies on local stem cell proliferation and differentiation which are processes that are tightly regulated by macrophages. Utilization of tissue-derived and ex-vivo expanded mesenchymal stromal cells (MSCs) in skeletal muscle regeneration has been heavily researched for the past decades but the results have not been consistent and the potential therapeutic mechanism or mechanisms remains unclear. In this project, we characterized the cell components of MSCs after inducing cell death under different conditions and confirmed their anti-inflammatory and pro-regenerative effects on macrophage polarization in vitro. We further investigated the underlying mechanisms of macrophage polarization by different components resulting from cell death. We found potent therapeutic effects from freeze and thaw (F&T) induced cell debris, and these effects are dependent on the externalization of phosphatidylserine (PtS) on the plasma membrane. In contrast, effects from the supernatant of F&T induced cell death primarily depends on the released protein content. Based on the findings from our in vitro studies, we applied the F&T induced cell supernatant to an animal model of peripheral artery disease (PAD) to treat muscle injury caused by a severe ischemia. This treatment resulted in significantly improved muscle functional and histological recovery as well as increased blood flow to the affected muscles 2 weeks after the injury procedure, validating the therapeutic potential of cell components of MSCs induced by F&T process, obviating the need for a viable cell population to treat injury. This result has implications for cell-free therapeutic approaches for ischemic injury to muscle.