Correction: Human adipose-derived mesenchymal stem cells for acute and sub-acute TBI.

[This corrects the article DOI: 10.1371/journal.pone.

Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model.

Traumatic brain injury (TBI) causes both physical disruption of the blood brain barrier (BBB) and altered immune responses that can lead to significant secondary brain injury and chronic inflammation within the central nervous system (CNS). Cell therapies, including mesenchymal stromal cells (MSC), have been shown to restore BBB integrity and augment endogenous splenic regulatory T cells (Treg), a subset of CD4+ T cells that function to regulate immune responses and prevent autoimmunity. We have recently shown that infusion of human cord blood-derived Treg decreased neuroinflammation after TBI in vivo and in vitro.

Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy.

The inflammatory response after traumatic brain injury (TBI) can lead to significant secondary brain injury and chronic inflammation within the central nervous system. Cell therapies, including mesenchymal stromal cells (MSC), have led to improvements in animal models of TBI and are under investigation in human trials. One potential mechanism for the therapeutic potential of MSC is their ability to augment the endogenous response of immune suppressive regulatory T cells (Treg).

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury.

The immune system plays critical roles in promoting tissue repair during recovery from neurotrauma but is also responsible for unchecked inflammation that causes neuronal cell death, systemic stress, and lethal immunodepression. Understanding the immune response to neurotrauma is an urgent priority, yet current models of traumatic brain injury (TBI) inadequately recapitulate the human immune response. Here, we report the first description of a humanized model of TBI and show that TBI places significant stress on the bone marrow.

Human adipose-derived mesenchymal stem cells for acute and sub-acute TBI.

In the U.S., approximately 1.

Human cord blood-derived regulatory T-cell therapy modulates the central and peripheral immune response after traumatic brain injury.

Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulate microglia activation and polarize them toward a reparative/anti-inflammatory phenotype have improved outcomes in preclinical models. However, no therapy to date has translated into proven benefits in human patients.

Procoagulant in vitro effects of clinical cellular therapeutics in a severely injured trauma population.

Clinical trials in trauma populations are exploring the use of clinical cellular therapeutics (CCTs) like human mesenchymal stromal cells (MSC) and mononuclear cells (MNC). Recent studies demonstrate a procoagulant effect of these CCTs related to their expression of tissue factor (TF). We sought to examine this relationship in blood from severely injured trauma patients and identify methods to reverse this procoagulant effect.

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges to Clinical Application.

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of models.

Pre-injury monocyte/macrophage depletion results in increased blood-brain barrier permeability after traumatic brain injury.

Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (M /M ) after a TBI may play an important role in preserving the blood-brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating M /M , we utilized a monocyte/macrophage depletion model in response to TBI in male rats.

Clinical Cellular Therapeutics Accelerate Clot Formation.

Clinical cellular therapeutics (CCTs) have shown preliminary efficacy in reducing inflammation after trauma, preserving cardiac function after myocardial infarction, and improving functional recovery after stroke. However, most clinically available cell lines express tissue factor (TF) which stimulates coagulation. We sought to define the degree of procoagulant activity of CCTs as related to TF expression.

Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury.

No current clinical intervention can alter the course of acute spinal cord injury (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells (MSCs) have been shown to modulate the injury sequelae of SCI largely via paracrine effects, although the mechanisms remain incompletely understood. One potential modality is through secretion of extracellular vesicles (EVs).

Inflammation-Stimulated Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Inflammation.

Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been proposed to be a key mechanistic link in the therapeutic efficacy of cells in response to cellular injuries through paracrine effects. We hypothesize that inflammatory stimulation of MSCs results in the release of EVs that have greater anti-inflammatory effects. The present study evaluates the immunomodulatory abilities of EVs derived from inflammation-stimulated and naive MSCs (MSCEv and MSCEv, respectively) isolated using a current Good Manufacturing Practice-compliant tangential flow filtration system.

Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal (GI) tract. Currently, it is treated with immunosuppressant or biologics that often induce severe adverse effects. Thus, there is an urgent clinical need for more specific treatments.

Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers.

Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier's surface and modulates its pharmacokinetics and biodistribution. Biomimicry-based approaches in nanotechnology attempt to imitate what happens in nature in order to transfer specific natural functionalities to synthetic nanoparticles.

Vascular Inflammation: A Novel Access Route for Nanomedicine.

Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD. In response to this new understanding, researchers are evaluating the potential cardiovascular benefits of new-generation therapies based on endogenous molecules with anti-inflammatory properties.

Local Inhibition of Macrophage and Smooth Muscle Cell Proliferation to Suppress Plaque Progression.

Atherosclerosis is a complex process responsible for a major burden of cardiovascular morbidity and mortality. Macrophages and smooth muscle cells (SMCs) are abundant within atherosclerotic plaques. This review discusses the role of macrophages and SMCs in plaque progression and provides an overview of nanoparticle-based approaches and other current methods for local targeting of atherosclerotic plaques.

Effects of the protein corona on liposome-liposome and liposome-cell interactions.

A thorough understanding of interactions occurring at the interface between nanocarriers and biological systems is crucial to predict and interpret their biodistribution, targeting, and efficacy, and thus design more effective drug delivery systems. Upon intravenous injection, nanoparticles are coated by a protein corona (PC). This confers a new biological identity on the particles that largely determines their biological fate.

The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery.

In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC).

Reconstructed stem cell nanoghosts: a natural tumor targeting platform.

The ultimate goal in cancer therapy is achieving selective targeting of cancer cells. We report a novel delivery platform, based on nanoghosts (NGs) produced from the membranes of mesenchymal stem cells (MSCs). Encompassing MSC surface molecules, the MSC-NGs retained MSC-specific in vitro and in vivo tumor targeting capabilities and were cleared from blood-filtering organs.