Browsing by Subject "Macrophages"

Now showing 1 - 4 of 4

Characterization of atherosclerotic plaques using ultrasound guided intravascular photoacoustic imaging
(2011-05) Wang, Bo, 1981-; Emelianov, Stanislav Y.; Sokolov, Konstantin; Smalling, Richard; Litovsky, Silvio; Dunn, Andrew; Aglyamov, Salavat
Rupture of atherosclerotic plaque is closely related to plaque composition. Currently, plaque composition cannot be clinically characterized by any imaging modality. The objective of this dissertation is to use a recently developed imaging modality – ultrasound-guided intravascular photoacoustic (IVPA) imaging – to detect the distribution of two critical components in atherosclerotic plaques: lipid and phagocytically active macrophages. Under the guidance of intravascular ultrasound imaging, spectroscopic IVPA imaging is capable of detecting the spatially resolving optical absorption property inside a vessel wall. In this study, contrast in spectroscopic IVPA imaging was provided by either the endogenous optical property of lipid or optically absorbing contrast agent such as gold nanoparticles (Au NPs). Using a rabbit model of atherosclerosis, this dissertation demonstrated that ultrasound guided spectroscopic IVPA imaging could simultaneously image lipid deposits as well as macrophages labeled in vivo with Au NPs. Information of macrophage activity around lipid rich plaques may help to identify rupture-prone or vulnerable plaques. The results show that ultrasound guided IVPA imaging is promising for detecting plaque composition in vivo. Clinical use of ultrasound guided IVPA imaging may significantly improve the accuracy of diagnosis and lead to more effective treatments of atherosclerosis.
The development of immunomodulatory approaches to restore skeletal muscle function after injury
(2015-05) Rybalko, Viktoriya Yurievna; Farrar, Roger P.; Suggs, Laura J; Brothers, Robert M; Thompson, Wesley J; Adamo, Martin L
Efficient restoration of skeletal muscle function after severe injury is a major goal of intervention therapies. Ischemia/reperfusion (I/R) injury to skeletal muscle leads to exaggerated inflammatory response and significant ultrastructural tissue damage slowing restoration of muscular structure and function. Herein, we used animal model of tourniquet-induced ischemia/reperfusion injury (TK-I/R) to test the effects of exogenously delivered growth factors and cells on skeletal muscle regeneration. The delivery of PEGylated fibrin along with stromal cell derived factor-1α and/or insulin-like growth factor-I into acutely injured muscle, differentially affected functional muscle regeneration. These data suggest that local balance and release kinetics of growth factors in the tissue microenvironment can significantly impact the success of skeletal muscle repair. Cell-mediated treatment of I/R-injured muscle demonstrated significant tissue regeneration using adoptively transferred and in vitro polarized macrophages. Functional activation status of transplanted macrophage populations impacted the outcome of muscle repair. We showed that increasing macrophage populations at the site of injury in temporally regulated manner is beneficial for efficient recovery of muscle force and function.
Electrophoretically decellularized xenogeneic extracellular matrix for large volume skeletal muscle regeneration
(2015-08) Merscham, Melissa Marie; Farrar, Roger P.; Suggs, Laura; Thompson, Wesley; Brothers, Robert; Baker, Aaron
Large volume skeletal muscle injuries, such as those that occur through traumatic or surgical means, are complex injuries that are unable to repair through the body’s native repair processes. These injuries, termed volumetric muscle loss (VML), result in fibrotic scar tissue formation and functional impairments. Within the last decade, there has been an immense push towards bioscaffold research and development to regenerate functional skeletal muscle tissue in VML injuries. The most promising bioscaffold is the use of a decellularized skeletal muscle-derived extracellular matrix (ECM). However, the use of skeletal muscle derived ECMs to replace lost tissues is limited by the inability to produce ECMs of clinically relevant sizes and shapes. Therefore, the purpose of this study was to develop an electrophoresis-based decellularization method that can render large volumes of porcine skeletal muscle ECM acellular time while also retaining the native ECM ultrastructure. Analysis of the resulting decellularized porcine skeletal muscle ECM determined most soluble proteins and DNA were removed, and the collagen framework of the ECM resembled that of native skeletal muscle. The decellularized ECM was implanted into a rodent lateral gastrocnemius (LGAS) VML injury model previously developed in our lab. Repair of the VML injury with the electrophoretically decellularized porcine ECM improved morphology of the LGAS and resulted in myofiber, blood vessel, and nerve growth throughout the ECM implant in vivo, and promoted an M2 macrophage profile. Addition of mesenchymal stem cells (MSCs) to the implanted ECM increased functional recovery, myofiber and blood vessel infiltration, and reduced fibrosis within the ECM implant region compared to saline treated implants 84 days after injury. The direct contribution of the injected MSCs tagged with green fluorescent protein (GFP) to myofiber development was not detected. These data demonstrate an electrophoresis-based decellularization protocol may be a better alternative to produce clinically relevant ECMs that can be used to repair VML injuries, and resulting porcine ECMs serve as a viable platform for muscle regeneration. Additionally, injection of MSCs into the ECM improves myofiber ingrowth, vascularization, and function most likely through modulation of the tissue microenvironment rather than differentiation and fusion into skeletal muscle.
Therapeutic potential of macrophages in ischemic skeltal muscle repair
(2016-08) Hsieh, Pei-Ling; Farrar, Roger P.; Suggs, Laura J.; Baker, Aaron B.; Thompson, Wesley J.; Stone, Audrey J.
Peripheral arterial disease (PAD) affects more than 8 million patients in the US. The gradual obstruction of blood supply causes skeletal muscle to degenerate and regenerate. Among various cells mediating these processes, it has been indicated that macrophages (MPs) are important for efficient muscle repair. In this project, we characterized the temporal transition of monocyte/ MP phenotype in muscle following ischemia in response to regenerative events to decide the timing of treatment. Then we tested the effect of MPs-mediated cell therapy through adoptive transfer of MPs in ischemic muscle. Our data showed that transplantation of in vitro polarized pro-inflammatory M1 MPs on day 1 post-FAE generated the best results with increased myofiber size, perfusion, capillary density and muscle contractile force. On the other hand, delivery of anti-inflammatory M2 MPs on day 3 post-FAE showed improvement of muscle recovery. In order to eliminate the cytokine manipulation, we exploited the immunoregulatory property of ASCs and examined the effect of co-delivering ASCs and unpolarized M0 MPs on ischemic muscle regeneration. Co-injection of ASCs and M0 MPs resulted in greatly improved muscle morphology and function with enhanced tissue perfusion. These data demonstrated that intramuscular administration of MPs hastened the muscle regeneration and may serve as a promising therapeutic approach for PAD.