Soluble components from mesenchymal stromal cell processing exert anti-inflammatory effects and facilitate ischemic muscle regeneration.

Background Aims: Skeletal muscle regeneration after severe damage is reliant on local stem cell proliferation and differentiation, processes that are tightly regulated by macrophages. Peripheral artery disease is a globally prevalent cardiovascular disease affecting millions of people. Progression of the disease leads to intermittent claudication, subsequent critical limb ischemia and muscle injury.

Apoptotic body-inspired nanoparticles target macrophages at sites of inflammation to support an anti-inflammatory phenotype shift.

Chronic inflammation is a significant pathological process found in a range of disease states. Treatments to reduce inflammation in this family of diseases may improve symptoms and disease progression, but are largely limited by variable response rates, cost, and off-target effects. Macrophages are implicated in many inflammatory diseases for their critical role in the maintenance and resolution of inflammation.

Cell-Inspired Biomaterials for Modulating Inflammation.

Inflammation is a crucial part of wound healing and pathogen clearance. However, it can also play a role in exacerbating chronic diseases and cancer progression when not regulated properly. A subset of current innate immune engineering research is focused on how molecules such as lipids, proteins, and nucleic acids native to a healthy inflammatory response can be harnessed in the context of biomaterial design to promote healing, decrease disease severity, and prolong survival.

Modulating inflammatory macrophages with an apoptotic body-inspired nanoparticle.

Macrophages play a critical role in the initiation, maintenance, and resolution of inflammation because of their diverse and plastic phenotypic responses to extracellular stimuli. Inflammatory stimuli drive the recruitment and activation of inflammatory (M1) macrophages, capable of significant cytokine production that potentiates inflammation. Local environmental signals including apoptotic cell efferocytosis drive a phenotypic transition toward pro-reparative (M2) macrophages to facilitate the resolution of inflammation.

Therapeutic assessment of mesenchymal stem cells delivered within a PEGylated fibrin gel following an ischemic injury.

The intent of the current study was to investigate the therapeutic contribution of MSCs to vascular regeneration and functional recovery of ischemic tissue. We used a rodent hind limb ischemia model and intramuscularly delivered MSCs within a PEGylated fibrin gel matrix. Within this model, we demonstrated that MSC therapy, when delivered in PEGylated fibrin, results in significantly higher mature blood vessel formation, which allows for greater functional recovery of skeletal muscle tissue as assessed using force production measurements.