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).

Human mesenchymal stromal cells attenuate graft-versus-host disease and maintain graft-versus-leukemia activity following experimental allogeneic bone marrow transplantation.

We sought to define the effects and underlying mechanisms of human, marrow-derived mesenchymal stromal cells (hMSCs) on graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity. Irradiated B6D2F1 mice given C57BL/6 BM and splenic T cells and treated with hMSCs had reduced systemic GvHD, donor T-cell expansion, and serum TNFα and IFNγ levels. Bioluminescence imaging demonstrated that hMSCs redistributed from lungs to abdominal organs within 72 hours, and target tissues harvested from hMSC-treated allogeneic BMT (alloBMT) mice had less GvHD than untreated controls.

Comparison of the effect of intra-tendon applications of recombinant human platelet-derived growth factor-BB, platelet-rich plasma, steroids in a rat achilles tendon collagenase model.

This study compared the effect of intra-tendon (IT) delivery of recombinant human platelet-derived growth factor-BB (rhPDGF-BB), platelet-rich plasma (PRP) and corticosteroids in a rat tendinopathy model. Seven days after collagenase induction of tendinopathy, a 30-µl IT injection was administered. Treatments included: saline; 3 µg rhPDGF-BB; 10 µg rhPDGF-BB; PRP; and 300 µg triamcinolone acetonide (TCA).

The role of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in orthopaedic bone repair and regeneration.

Recombinant human PDGF BB homodimer (rhPDGF-BB) is a potent recruiter of, and strong mitogenic factor for, cells crucial to musculoskeletal tissue repair, including mesenchymal stem cells (MSCs), osteogenic cells and tenocytes. rhPDGF-BB also upregulates angiogenesis. These properties allow rhPDGF-BB to trigger the cascade of bone and adjoining soft tissue repair and regeneration.

Assessing adipogenic potential of mesenchymal stem cells: a rapid three-dimensional culture screening technique.

Bone-marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate into a number of phenotypes, including adipocytes. Adipogenic differentiation has traditionally been performed in monolayer culture, and, while the expression of a fat-cell phenotype can be achieved, this culture method is labor and material intensive and results in only small numbers of fragile adherent cells, which are not very useful for further applications. Aggregate culture is a cell-culture technique in which cells are induced to form three-dimensional aggregates; this method has previously been used successfully, among others, to induce and study chondrogenic differentiation of MSCs.

Effect of implantation of Augment(®) Bone Graft on serum concentrations of platelet-derived growth factors: a pharmacokinetic study.

Background: Augment(®) Bone Graft is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Augment(®) Bone Graft is a combination device comprised of beta-tricalcium phosphate (β-TCP) and recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB).

Objective: This human pharmacokinetic study was undertaken to assess the effect of Augment(®) Bone Graft implantation on the serum concentration of platelet-derived growth factors (PDGFs).

Prostaglandin E2: a putative potency indicator of the immunosuppressive activity of human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are non-hematopoietic, pluripotent cells that give rise to stromal cells in the marrow. MSCs have been shown to be immunosuppressive and have become an attractive therapeutic option for the modulation of undesired immune responses. Currently, ex vivo expanded human (h)MSCs are being utilized in clinical trials both in the USA and in Europe to treat a variety of immune disorders.

Safety of recombinant human platelet-derived growth factor-BB in Augment(®) Bone Graft.

This article discusses nonclinical and clinical data regarding the safety of recombinant human platelet-derived growth factor-BB as a component of the Augment(®) Bone Graft (Augment). Augment is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Nonclinical studies included assessment of the pharmacokinetic profile of intravenously administered recombinant human platelet-derived growth factor-BB in rat and dog, effects of intravenous administration of recombinant human platelet-derived growth factor-BB in a reproductive and development toxicity study in rats, and chronic toxicity and carcinogenicity of Augment in a 12-month implantation model.

Growth factors and craniofacial surgery.

The specialty of craniofacial surgery is broad and includes trauma, aesthetics, reconstruction of congenital deformities, and regeneration of tissues. Moreover, craniofacial surgery deals with a diverse range of tissues including both "soft" and "hard" tissues. Technological advances in materials and biological sciences and improved surgical techniques have remarkably improved clinical outcomes.

Regenerative tendon and ligament healing: opportunities with recombinant human platelet-derived growth factor BB-homodimer.

Intrinsic tendon healing in response to injury is a reparative process that often results in formation of scar tissue with functional and mechanical properties inferior to those of the native tendon. Development of therapies that can promote regenerative, rather than reparative, healing hold the promise of improving patient recovery from tendon and ligament injuries by producing tissue that is morphologically and functionally equivalent to the native tissue. One therapeutic approach that has been a frequent topic of investigation in the preclinical literature is the use of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) to augment tendon and ligament repair.

Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response.

Amniotic fluid stem (AFS) cells are broadly multipotent, can be expanded extensively in culture, are not tumorigenic and can be readily cryopreserved for cell banking. Mesenchymal stem cells (MSC) show immunomodulatory activity and secrete a wide spectrum of cytokines and chemokines that suppress inflammatory responses, block mixed lymphocyte reactions (MLR) and other immune reactions, and have proven therapeutic against conditions such as graft-versus-host disease. AFS cells resemble MSCs in many respects including surface marker expression and differentiation potential.

Augment bone graft products compare favorably with autologous bone graft in an ovine model of lumbar interbody spine fusion.

Study Design: This study was designed to determine whether Augment Bone Graft (Augment, Biomimetic Therapeutics, Inc., Franklin, TN) and Augment Injectable Bone Graft (Augment Injectable, Biomimetic Therapeutics, Inc., Franklin, TN), 2 combination devices comprising recombinant human platelet-derived growth factor-BB and β-tricalcium phosphate-containing matrices, promote bone bridging in an ovine model of lumbar spine fusion.

Fibroblast Growth Factor-2 Enhances Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells without Diminishing Their Immunosuppressive Potential.

Allogeneic hematopoietic stem cell transplantation is the main curative therapy for many hematologic malignancies. Its potential relies on graft-versus-tumor effects which associate with graft-versus-host disease. Mesenchymal stromal cells (MSCs) possess immunomodulatory properties that make them attractive therapeutic alternatives.

Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks.

It is well known that adult cartilage lacks the ability to repair itself; this makes articular cartilage a very attractive target for tissue engineering. The majority of articular cartilage repair models attempt to deliver or recruit reparative cells to the site of injury. A number of efforts are directed to the characterization of progenitor cells and the understanding of the mechanisms involved in their chondrogenic differentiation.

High-resolution kinetics of cytokine signaling in human CD34/CD117-positive cells in unfractionated bone marrow.

Cytokine-mediated phosphorylation of Erk (pErk), ribosomal S6 (pS6), and Stat5 (pStat5) in CD34(+)/CD117(+) blast cells in normal bone marrow from 9 healthy adult donors were analyzed over 60 minutes. Treatment with stem cell factor (SCF), Flt3-ligand (FL), IL-3, and GM-CSF and measurement by multiparametric flow cytometry yielded distinctive, highly uniform phosphoprotein kinetic profiles despite a diverse sample population. The correlated responses for SCF- and FL-stimulated pErk and pS6 were similar.

Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis.

Human mesenchymal stem cells (hMSCs) are being considered for clinical trials of multiple sclerosis (MS). We examined the effects of adult bone marrow-derived hMSCs on responses of primary human Th1, Th17, and Th1/17 double-expressing T-cell subsets, all implicated in MS. As expected, soluble products from hMSCs inhibited Th1 responses; however, Th17 responses were increased.

Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: current impact and future directions.

Regenerative stromal cell therapy (RSCT) has the potential to become a novel therapy for preventing and treating acute graft-versus-host disease (GVHD) in the allogeneic hematopoietic stem cell transplant (HSCT) recipient. However, enthusiasm for using RSCT in allogeneic HSCT has been tempered by limited clinical data and poorly defined in vivo mechanisms of action. As a result, the full clinical potential of RSCT in supporting hematopoietic reconstitution and as treatment for GVHD remains to be determined.

Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells.

We compared human mesenchymal stem cells (hMSCs), expanded long term with and without fibroblast growth factor (FGF) supplementation, with respect to proliferation, and the ability to undergo chondrogenesis in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than the control cells. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at all passages tested although, in some preparations, differentiation was diminished after seventh passage.

Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging.

Mesenchymal stem cells (MSCs) can differentiate into osteogenic, adipogenic, chondrogenic, myocardial, or neural lineages when exposed to specific stimuli, making them attractive for tissue repair and regeneration. We have used reporter gene-based imaging technology to track MSC transplantation or implantation in vivo. However, the effects of lentiviral transduction with the fluc-mrfp-ttk triple-fusion vector on the transcriptional profiles of MSCs remain unknown.

Long-lasting multiagent chemotherapy in adult high-risk Ewing's sarcoma of bone.

The outcome of Ewing's sarcoma depends on the anatomical site of the tumor. Studies conducted in high-risk patients are limited. We evaluated the outcome of high-risk Ewing's sarcoma patients that received long-term treatment protocol.

Unusual severe complication following transarterial chemoembolization for metastatic malignant melanoma: giant intrahepatic cyst and fatal hepatic failure.

We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material.

Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults.

The dose of graft-nucleated cells and CD34(+) haematopoietic progenitor cells are predictors of allogeneic engraftment and survival in umbilical cord blood (UCB) recipients. In this single institution prospective phase II trial, flow cytometric analyses of CD34(+) progenitor and lymphocyte populations in unmodified single unit human leucocyte antigen (HLA)-disparate UCB grafts infused into 31 consecutive adults (median age 41 years, range 20-64) receiving myeloablative conditioning were compared with clinical outcomes. Median infused UCB graft-nucleated cells and CD34(+) dose was 2.

Simplification of aggregate culture of human mesenchymal stem cells as a chondrogenic screening assay.

Aggregate culture provides a three-dimensional (3-D) environment for differentiating or differentiated cells; it is particularly useful to study in vitro chondrogenesis and cartilage biology. We have recently ported this method from a conical tube-based format to a 96-well plate format for the study of mesenchymal stem cell (MSC) chondrogenesis. The microplate format has greatly reduced the workload and materials cost, while maintaining reproducible chondrogenic differentiation.