Chondrogenic potential of mesenchymal stem cells from patients with rheumatoid arthritis and osteoarthritis: measurements in a microculture system.

BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct mesenchymal tissues; including cartilage and bone, they can be an attractive cell source for cartilage tissue engineering approaches. Our objective here was to compare the in vitro chondrogenic potential of MSCs isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) with cells from normal donors. METHODS: Marrow samples were removed during bone surgery and adherent cell cultures were established. The cells were then passed into a newly developed microaggregate culture system in a medium containing transforming growth factor beta3, insulin, dexamethasone and/or demineralized bone matrix. In vitro chondrogenic activity was measured as metabolic sulfate incorporation and type II collagen expression in pellet cultures. RESULTS: Culture-expanded MSCs from RA and OA patients did not differ significantly from the normal population with respect to their chondrogenic potential in vitro. Capability of total protein and proteoglycan synthesis as well as collagen II mRNA expression by cell aggregates was similar for all cell preparations in the presence of the appropriate growth and differentiation factors. Chondroprotective drugs such as chondroitin sulfate and glucosamine enhanced, whereas chloroquine inhibited chondrogenesis in normal donor-derived or patient-derived MSC cultures. Galectin-1, a beta-galactoside-binding protein with marked anti-inflammatory activity, stimulated the chondrogenic differentiation of mesenchymal cells in low (<2 microg/ml) concentration. DISCUSSION: These findings show that MSCs from RA and OA patients possess similar chondrogenic potential as MSCs isolated from healthy donors, therefore these cells may serve as a potential new prospect in cartilage replacement therapy.

[Mesenchymal stem cells and the immune system--immunosuppression without drugs?]. / A mesenchymalis ôssejtek és az immunrendszer--immunszuppresszió gyógyszerek nélkül?

Mesenchymal stem cells (MSC) - isolated from various tissues in humans and other species - are one of the most promising adult stem cell types due to their availability and the relatively simple requirements for in vitro expansion. They have the capacity to differentiate into several tissues, including bone, cartilage, tendon, muscle and adipose, and produce growth factors and cytokines that promote hematopoietic cell expansion and differentiation. In vivo, MSCs are able to repair damaged tissue from kidney, heart, liver, pancreas and gastrointestinal tract. Furthermore, they also have anti-proliferative, immunomodulatory and anti-inflammatory effects, but evoke only little immune reactivity. Although the mechanism underlying the immunosuppressive effects of MSCs has not been clearly defined, their immunosuppressive properties have already been exploited in the clinical setting. Therefore, in the future, MSCs might have implications for treatment of allograft rejection, graft-versus-host disease, rheumatoid arthritis, autoimmune inflammatory bowel disease and other disorders in which immunomodulation and tissue repair are required. The aim of this review is to critically analyze the field of MSC biology, particularly with respect to their immunomodulatory properties and potential clinical use in the future.

A novel anti-inflammatory function of human galectin-1: inhibition of hematopoietic progenitor cell mobilization.

OBJECTIVE: The immunosuppressive and anti-inflammatory activity of mammalian galectin-1 (Gal-1) has been well established in experimental in vivo animal models and in vitro studies. Since the proliferation and migration of leukocytes represent a necessary and important step in response to the inflammatory insult, we have investigated whether Gal-1 affects the mobilization of hematopoietic progenitor cells (HPC) induced by cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF). METHODS: Bone marrow HPCs were mobilized with CY/G-CSF or CY/G-CSF plus human recombinant Gal-1 in BDF1 mice. Bone marrow (BM) and blood cells were taken at different time points and analyzed for their in vivo repopulating ability in lethally irradiated syngeneic animals. The number of myeloid progenitor cells in BM and blood samples was determined by colony-forming cell assay. Expression of surface markers (Sca-1, CD3epsilon, CD45R/B220, Ter-119, GR-1, and CD11b) on nucleated marrow cells was measured by flow cytometry. The lymphocytes, granulocytes, and monocytes in blood samples were counted after Giemsa staining. RESULTS: Gal-1 dramatically inhibited CY/G-CSF-induced HPC migration to the periphery as well as decreased peripheral neutrophilia and monocytosis in a dose- and time-dependent manner. In contrast, Gal-1 itself stimulated HPC expansion and accumulation within the BM. The presence of the lectin for inhibition of HPC mobilization was essential during the second half of the treatment. Moreover, Gal-1 inhbited transendothelial migration of BM-derived HPCs in response to SDF-1 in vitro. CONCLUSION: Gal-1 blocked BM progenitor cell migration induced by CY/G-CSF treatment, indicating a novel anti-inflammatory function of the lectin. We suggest that the inhibition of HPC mobilization occurs mainly via obstructing the transendothelial migration of BM-derived cells including primitive hematopoietic and committed myeloid progenitor cells and mature granulocytes and monocytes.

[Mesenchymal stem cells as potential source cartilage repair]. / A mesenchymalis ossejtek felhasználáisainak lehetoségei a porckárosodással járó mozgásszervi betegségek kezelésében.

Articular cartilage damaged by disease or trauma has a limited capacity for regeneration. The end stage of cartilage loss frequently leads to osteoarthritis resulting in a significantly decreased quality of life in millions of people. The surgical treatment of articular cartilage injury has always posed difficult problems for orthopedic surgeons and regarding long-term outcomes the currently available methods are unsatisfactory. The main lack of the applied methods is the appearance of the mechanically inadequate resident fibrocartilage instead of hyalin cartilage in the place of the cartilage defect. To find reliable methods for early repair of cartilage injuries seems of huge importance. Using techniques of tissue engineering, artificial cartilage fabricated in vitro has been applied for the repair and regeneration of damaged cartilage. Mesenchymal stem cells provide a source of cells for the repair of musculoskeletal tissue. Mesenchymal stem cells are multipotent cells that are capable of differentiating into cartilage, tendon, muscle, cartilage or hematopoiesis supporting marrow stroma. To ensure the successful durable integration and function of the engineered tissue requires suitable biomechanical and biochemical circumstances, and poses the challenge of handling in vitro culture of human cells, cell biology and molecular biology.

Biphasic effect of recombinant galectin-1 on the growth and death of early hematopoietic cells.

Galectin-1 is a member of the family of beta-galactoside binding animal lectins, galectins. Its presence in the bone marrow has been detected; however, its role in the regulation of hematopoiesis is unknown. In the present study, we have evaluated the effect of recombinant human galectin-1 on the proliferation and survival of murine and human hematopoietic stem and progenitor cells. We show that low amount of galectin-1 (10 ng/ml) increases the formation of granulocyte-macrophage and erythroid colonies and the frequencies of day-7 cobblestone area-forming cells on a lactose-inhibitable fashion. In contrast, high amount of galectin-1 (10 microg/ml) dramatically reduces the growth of the committed blood-forming progenitor cells as well as the much younger, lineage-negative hematopoietic cells (day-28 to -35 cobblestone area-forming cells). This inhibition is not blocked by lactose and, therefore, is largely independent of the beta-galactoside-binding site of the lectin. Furthermore, assays to detect apoptosis render it likely that the high amount of galectin-1 acts as a classical proapoptotic factor for the premature hematopoietic cells.