Kindlin-3 mutation in mesenchymal stem cells results in enhanced chondrogenesis.

Identifying patient mutations driving skeletal development disorders has driven our understanding of bone development. Integrin adhesion deficiency disease is caused by a Kindlin-3 (fermitin family member 3) mutation, and its inactivation results in bleeding disorders and osteopenia. In this study, we uncover a role for Kindlin-3 in the differentiation of bone marrow mesenchymal stem cells (BMSCs) down the chondrogenic lineage.

The Habitat Assay, a Platform to Study Properties of Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are at the forefront as therapeutic tools for an extensive number of tissue engineering and regenerative medicine applications. MSC differentiation properties have been extensively studied by this laboratory and many others. The generation and validation of potency assays would be a valuable tool for the study of cellular properties relevant for applications.

Human and Rat Bone Marrow-Derived Mesenchymal Stem Cells Differ in Their Response to Fibroblast Growth Factor and Platelet-Derived Growth Factor.

Tissue engineering requires large numbers of cells with enhanced differentiation properties. Thus, the effect of expansion conditions must be explored. Human and rat marrow-derived mesenchymal stem cells (hMSCs and rMSCs, respectively) were comparatively culture expanded through seven passages in the presence of either fibroblast growth factor-2 (FGF-2) or platelet-derived growth factor BB (PDGF-BB).

Mesenchymal Stem Cell Soluble Mediators and Cystic Fibrosis.

Human Mesenchymal stem cells (hMSCs) secrete products (supernatants) that are anti-inflammatory and antimicrobial. We have previously shown that hMSCs decrease inflammation and infection in the murine model of Cystic Fibrosis (CF). Cystic Fibrosis (CF) is a genetic disease in which pulmonary infection and inflammation becomes the major cause of morbidity and mortality.

Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment.

Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in the in vivo murine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness using Pseudomonas aeruginosa (gram negative bacteria) and Staphylococcus aureus (gram positive bacteria).

Validating continuous digital light processing (cDLP) additive manufacturing accuracy and tissue engineering utility of a dye-initiator package.

This study tested the accuracy of tissue engineering scaffold rendering via the continuous digital light processing (cDLP) light-based additive manufacturing technology. High accuracy (i.e.

The effects of crosslinking of scaffolds engineered from cartilage ECM on the chondrogenic differentiation of MSCs.

Scaffolds fabricated from cartilage extracellular matrix provide a chondroinductive environment that stimulates cartilaginous matrix synthesis in a variety of cell types. A limitation of these cartilage-derived matrix (CDM) scaffolds is that they contract during in vitro culture, which unpredictably alters their shape. The current study examined the hypothesis that collagen crosslinking techniques could inhibit cell-mediated contraction of CDM scaffolds.

Growth, differentiation capacity, and function of mesenchymal stem cells expanded in serum-free medium developed via combinatorial screening.

The presence of serum in cell culture medium presents an obstacle to safe and efficient production of hMSCs for therapeutic purposes. Availability of defined medium will be crucial to elucidating the mechanism of action of hMSCs in many indications as well as a prerequisite to consistently produce cells with predictable performance characteristics. Using a bioinformatics driven approach, which we call the BD Discovery Platform, we have developed a novel serum-free medium that supports highly efficient growth while maintaining the surface markers and functional characteristics defining hMSCs.

Efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities.

Long-term lentiviral transduction of human mesenchymal stem cells (hMSCs) greatly enhances the usefulness of these cells. However, such transduction currently requires the use of polybrene, which severely inhibits hMSC proliferation. In contrast, protamine sulfate at 100 μg/ml doubled transduction efficiencies without affecting proliferation or differentiation potential.

The effect of extended first passage culture on the proliferation and differentiation of human marrow-derived mesenchymal stem cells.

Human marrow-derived mesenchymal stem cells (hMSCs) have been investigated for more than 20 years. They have been shown to be therapeutic in a number of animal models and are currently in use in more than 200 clinical trials, thus documenting their importance in the field of translational medicine. Standard protocols for the passage and collection of hMSCs involve trypsinization of preconfluent cultures.

The inhibition by interleukin 1 of MSC chondrogenesis and the development of biomechanical properties in biomimetic 3D woven PCL scaffolds.

Tissue-engineered constructs designed to treat large cartilage defects or osteoarthritic lesions may be exposed to significant mechanical loading as well as an inflammatory environment upon implantation in an injured or diseased joint. We hypothesized that a three-dimensionally (3D) woven poly(ε-caprolactone) (PCL) scaffold seeded with bone marrow-derived mesenchymal stem cells (MSCs) would provide biomimetic mechanical properties in early stages of in vitro culture as the MSCs assembled a functional, cartilaginous extracellular matrix (ECM). We also hypothesized that these properties would be maintained even in the presence of the pro-inflammatory cytokine interleukin-1 (IL-1), which is found at high levels in injured or diseased joints.

Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.

Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons.

Defining human mesenchymal stem cell efficacy in vivo.

Allogeneic human mesenchymal stem cells (hMSCs) can suppress graft versus host disease (GvHD) and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo.

Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.

The potential of mesenchymal stem cells for neural repair.

Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults.

Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix.

Objectives: Adipose-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (MSCs) are multipotent adult stem cells with potential for use in cartilage tissue engineering. We hypothesized that these cells show distinct responses to different chondrogenic culture conditions and extracellular matrices, illustrating important differences between cell types.

Methods: Human ASCs and MSCs were chondrogenically differentiated in alginate beads or a novel scaffold of reconstituted native cartilage-derived matrix with a range of growth factors, including dexamethasone, transforming growth factor beta3, and bone morphogenetic protein 6.

A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans.

Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III).

Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis.

Cell-based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow-derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response.

MSC frequency correlates with blood vessel density in equine adipose tissue.

Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity to develop into different mature mesenchymal cell types. They were originally isolated from bone marrow, but MSC-like cells have also been isolated from other tissues. The common feature of all of these tissues is that they all house blood vessels.

Effects of initial seeding density and fluid perfusion rate on formation of tissue-engineered bone.

We describe a novel bioreactor system for tissue engineering of bone that enables cultivation of up to six tissue constructs simultaneously, with direct perfusion and imaging capability. The bioreactor was used to investigate the relative effects of initial seeding density and medium perfusion rate on the growth and osteogenic differentiation patterns of bone marrow-derived human mesenchymal stem cells (hMSCs) cultured on three-dimensional scaffolds. Fully decellularized bovine trabecular bone was used as a scaffold because it provided suitable "biomimetic" topography, biochemical composition, and mechanical properties for osteogenic differentiation of hMSCs.

Human mesenchymal stem cells signals regulate neural stem cell fate.

Neural stem cells (NSCs) differentiate into neurons, astrocytes and oligodendrocytes depending on their location within the central nervous system (CNS). The cellular and molecular cues mediating end-stage cell fate choices are not completely understood. The retention of multipotent NSCs in the adult CNS raises the possibility that selective recruitment of their progeny to specific lineages may facilitate repair in a spectrum of neuropathological conditions.

Effect of transforming growth factor beta 2 on marrow-infused foam poly(propylene fumarate) tissue-engineered constructs for the repair of critical-size cranial defects in rabbits.

This study investigates the osseointegration of poly(propylene fumarate) (PPF) with beta-tricalcium phosphate (beta-TCP) scaffolds in a critical-size (diameter, 1.6 cm), cranial defect in 4-month-old rabbits (n = 51), killed at 6 or 12 weeks. Two molecular weights of PPF were used to produce bilayer scaffolds with 0.

Adult stem cell driven genesis of human-shaped articular condyle.

Uniform design of synovial articulations across mammalian species is challenged by their common susceptibility to joint degeneration. The present study was designed to investigate the possibility of creating human-shaped articular condyles by rat bone marrow-derived mesenchymal stem cells (MSCs) encapsulated in a biocompatible poly(ethylene glycol)-based hydrogel. Rat MSCs were harvested, expanded in culture, and treated with either chondrogenic or osteogenic supplements.