Intravenous Autologous Bone Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns.

Freeze-dried platelets are a promising alternative in bleeding thrombocytopenic patients with hematological malignancies.

Thrombosomes are trehalose-stabilized, freeze-dried group O platelets with a 3-year shelf life. They can be stockpiled, rapidly reconstituted, and infused regardless of the recipient's blood type. Thrombosomes thus represent a potential alternative platelet transfusion strategy.

Freeze-dried platelets promote clot formation, attenuate endothelial cell permeability, and decrease pulmonary vascular leak in a murine model of hemorrhagic shock.

Background: Hemorrhagic shock (HS) and trauma induce endothelial barrier compromise, inflammation, and aberrant clotting. We have shown that fresh human platelets (Plts) and Plt extracellular vesicles mitigate vascular leak in murine models of injury. Here, we investigate the potential of freeze-dried platelets (FDPlts) to attenuate pulmonary vascular permeability, decrease inflammation, and promote clotting in a murine model of HS.

Evaluation of sepsis using compensatory reserve measurement: A prospective clinical trial.

Background: Sepsis, a leading cause of morbidity and mortality worldwide, characterized by metabolic and hemodynamic changes that can lead to multiorgan failure and death. The evaluation of a patient's condition is routinely performed by several objective criteria. The compensatory reserve measurement (CRM) represents a new paradigm that measures the total of all physiological compensatory mechanisms, using noninvasive photoplethysmography to read changes in arterial waveforms.

Cryopreserved mesenchymal stem cells regain functional potency following a 24-h acclimation period.

Background: Mesenchymal stem cells (MSCs) are attractive cell-therapy candidates. Despite their popularity and promise, there is no uniform method of preparation of MSCs. Typically, cells are cryopreserved in liquid nitrogen, thawed, and subsequently administered to a patient with little to no information on their function post-thaw.

Prehospital trauma experience of the Israel defense forces on the Syrian border 2013-2017.

Background: The Israeli Defense Force Medical Corps (IDF-MC) is routinely collecting prehospital data to establish a prehospital registry. Since February 2013, Israel has been providing medical care to Syrian refugees. This unique humanitarian aid begins in prehospital settings and typically culminates in Israeli civilian hospitals.

Mesenchymal Stem Cells Reconditioned in Their Own Serum Exhibit Augmented Therapeutic Properties in the Setting of Acute Respiratory Distress Syndrome.

Mesenchymal stem cells (MSCs) are a promising form of therapy for acute respiratory distress syndrome (ARDS). The objective of this study was twofold: (a) to characterize cytokine expression in serum from ARDS subjects receiving MSCs and (b) to determine MSC function following "preconditioning" with ARDS serum. In phase I, serum from three cohorts of animals (uninjured [no ARDS, n = 4], injured untreated [n = 5], and injured treated with approximately 6 million per kilogram MSCs [n = 7]) was analyzed for expression of inflammatory mediators.

Preconditioning in an Inflammatory Milieu Augments the Immunotherapeutic Function of Mesenchymal Stromal Cells.

Multipotent mesenchymal stromal cells (MSCs) have emerged as potent therapeutic agents for multiple indications. However, recent evidence indicates that MSC function is compromised in the physiological post-injury milieu. In this study, bone marrow (BM)- and adipose-derived (AD)-MSCs were preconditioned in hypoxia with or without inflammatory mediators to potentiate their immunotherapeutic function in preparation for in vivo delivery.

Bench-to-bedside optimization of mesenchymal stem cell isolation, processing, and expansion for administration.

In this study, we aimed at identifying the optimal conditions for isolation, processing and expansion of mesenchymal stem cells (MSCs). Porcine bone marrow was obtained from either small- or large-volume bone marrow aspirate (BMA). Next, three BMA processing methods were compared.

Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease.

Multipotent mesenchymal stem/stromal cells (MSCs) possess robust self-renewal characteristics and the ability to differentiate into tissue-specific cells. Their therapeutic potential appears promising as evident from their efficacy in several animal models of pulmonary disorders as well as early-phase clinical trials of acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). Such therapeutic efficacy might be attributed to MSC-derived products (the "secretome"), namely conditioned media (CM) and extracellular vesicles (EVs), which have been shown to play pivotal roles in the regenerative function of MSCs.

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells.

Background: In the bone marrow, MSCs reside in a hypoxic milieu (1-5% O) that is thought to preserve their multipotent state. Typically, in vitro expansion of MSCs is performed under normoxia (~ 21% O), a process that has been shown to impair their function. Here, we evaluated the characteristics and function of MSCs cultured under hypoxia and hypothesized that, when compared to normoxia, dedicated hypoxia will augment the functional characteristics of MSCs.

The effect of acute respiratory distress syndrome on bone marrow-derived mesenchymal stem cells.

Background: It is known that, following a physiological insult, bone marrow-derived mesenchymal stem cells (MSCs) mobilize and home to the site of injury. However, the effect of injury on the function of endogenous MSCs is unknown. In this study, MSCs harvested from the bone marrow of swine with or without acute respiratory distress syndrome (ARDS) were assessed for their characteristics and therapeutic function.

Antibiotic Treatment - What Can Be Learned from Point of Injury Experience?

Introduction: Early antibiotic administration after trauma reduces infection rates of open wounds. A clinical practice guideline (CPG) was created to ensure that wounded personnel who are not expected to arrive at the hospital within an hour receive antibiotic treatment in the field. This study evaluated how well-advanced life saver (ALS) providers complied with Israeli Defense Force (IDF) CPG.

The promise of mesenchymal stem cell therapy for acute respiratory distress syndrome.

This review describes the current state of the science on mesenchymal stem cell (MSC) treatment for acute lung injury (ALI). The general characteristics, regenerative potential, and mechanism of action of MSCs are first presented. Next, particular emphasis is placed on the application of MSCs for the treatment of acute respiratory distress syndrome (ARDS) in preclinical and clinical studies.

Battlefield pain management: A view of 17 years in Israel Defense Forces.

Background: Pain control in trauma is an integral part of treatment in combat casualty care (CCC). More soldiers injured on the battlefield will need analgesics for pain than those who will need lifesaving interventions (LSI). It has been shown that early treatment of pain improves outcomes after traumatic injury, whereas inadequate treatment leads to higher rates of PTSD.

Analysis of injury patterns and roles of care in US and Israel militaries during recent conflicts: Two are better than one.

Background: As new conflicts emerge and enemies evolve, military medical organizations worldwide must adopt the "lessons learned." In this study, we describe roles of care (ROCs) deployed and injuries sustained by both US and Israeli militaries during recent conflicts. The purpose of this collaborative work is facilitate exchange of medical data among allied forces in order to advance military medicine and facilitate strategic readiness for future military engagements that may involve less predictable situations of evacuation and care, such as prolonged field care.

Controlling Arteriogenesis and Mast Cells Are Central to Bioengineering Solutions for Critical Bone Defect Repair Using Allografts.

Although most fractures heal, critical defects in bone fail due to aberrant differentiation of mesenchymal stem cells towards fibrosis rather than osteogenesis. While conventional bioengineering solutions to this problem have focused on enhancing angiogenesis, which is required for bone formation, recent studies have shown that fibrotic non-unions are associated with arteriogenesis in the center of the defect and accumulation of mast cells around large blood vessels. Recently, recombinant parathyroid hormone (rPTH; teriparatide; Forteo) therapy have shown to have anti-fibrotic effects on non-unions and critical bone defects due to inhibition of arteriogenesis and mast cell numbers within the healing bone.

BMP6-Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study.

Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF), suffer grave financial and clinical burden. Current clinical treatments focus on symptoms' management but do not combat the issue at the source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing the BMP6 gene (MSC-BMP6), were suspended in fibrin gel and implanted into a vertebral defect to investigate their effect on bone regeneration in a clinically relevant, large animal pig model.

PTH Induces Systemically Administered Mesenchymal Stem Cells to Migrate to and Regenerate Spine Injuries.

Osteoporosis affects more than 200 million people worldwide leading to more than 2 million fractures in the United States alone. Unfortunately, surgical treatment is limited in patients with low bone mass. Parathyroid hormone (PTH) was shown to induce fracture repair in animals by activating mesenchymal stem cells (MSCs).

Stromal-cell-derived extracellular matrix promotes the proliferation and retains the osteogenic differentiation capacity of mesenchymal stem cells on three-dimensional scaffolds.

To date, expansion of bone-marrow-derived mesenchymal stem cells (MSCs) is typically carried out on two-dimensional (2D) tissue culture plastic. Since this 2D substratum is very different from the physiological situation, MSCs gradually lose their unique multipotent properties during expansion. Recently, the role of the extracellular matrix (ECM) microenvironment ("niche") in facilitating and regulating stem cell behavior in vivo has been elucidated.

Stem cell therapy for osteoporosis.

Osteoporosis is a debilitating disease that affects millions of people worldwide. Current osteoporosis treatments are predominantly bone-resorbing drugs that are associated with several side effects. The use of stem cells for tissue regeneration has raised great hope in various fields of medicine, including musculoskeletal disorders.

Biomimetic collagen-hydroxyapatite composite fabricated via a novel perfusion-flow mineralization technique.

Prevalent three-dimensional scaffolds for bone tissue engineering are mineralized collagen-hydroxyapatite (Col/HA) composites. Conventional mineralization techniques are either to coat collagen scaffold surfaces with minerals or to simply mix collagen and mineral nanoparticles together. These conventional in vitro collagen mineralization methods are different from the in vivo bone formation process and often result in scaffolds that are not suitable for bone tissue engineering.