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Results for “Bone marrow mesenchymal stem cells”

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At least 19 recordsLinked to original sources

PubMed2005

Integral therapeutic potential of bone marrow mesenchymal stem cells.

Bone marrow derived mesenchymal stem cells (MSC) are adult stem cells that reside within the bone marrow compartment. In the traditional developmental model, adult stem cells are able to differentiate only to the tissue in which they reside. Recent data have challenged the committed fate of the adult stem cells, presenting evidence for their multi-lineage differentiation potential. In addition, potential therapeutic benefits of MSC administration have been the main concern of much research, including clinical trials. These studies promote adult stem cell therapy by shedding some light on the therapeutic potential of MSC and their mechanism of action. Many doubts have found their way into MSC research. They question MSC potency and beneficial contribution. However, these obstacles should not arrest but set a challenge to MSC researchers to examine their achievements under a magnifying glass. Therapeutic benefits of MSC exogenous delivery do not run counter to its possible participation in endogenous repair. Several reports imply MSC involvement in physiological repair but no explicit data support this hypothesis. This review tries to put MSC research into perspective. Possible therapeutic applications of MSC therapy for damaged tissue replacement, tissue engineering and the underlying repair mechanisms will be discussed. In addition, reported data about MSC possible involvement in physiological multiple tissue repair, their homing to injury and site-specific differentiation will be presented.

Animals↗

PubMed2005

Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells.

Bone marrow (BM) mesenchymal stem cells (MSCs) are cells capable of expanding and differentiating in vitro into nonhematopoietic cells. Neurotrophic cytokines, such as human epidermal growth factor (hEGF) and bovine fibroblast growth factor (bFGF) can induce differentiation into neural cells (NCs). When BM MSCs were cultured with hEGF and bFGF, RNA expression of neuronal specific markers Nestin, MAP-2, and tyrosine hydroxylase (TH) were observed. We tested a new cytokine combination to generate mature NCs. The plastic-adherent cells were collected and then split when they were 90% confluent from an enriched mononuclear cell layer. At passage 3, MSCs were cultured in neural differentiation media (dbcAMP, IBMX, FGF-8, BDNF, hEGF, and bFGF in NEUROBASAL media plus B27). Cells were counted on day 6. Immunofluorescent staining and reverse transcriptase (RT)-PCR were performed to evaluate the expression of neural markers. On day 6, 66% of cells developed dendrites and presented typical neural cell morphology. Some cells were positive for early neural markers Nestin and beta-tubulin III. Cells expressing mature neuronal markers (NF, NeuN, Tau, Nurr1, GABA, oligodendryte GalC, and glial GFAP) were also seen. By adding hEGF, bFGF, dbcAMP, IBMX, BDNF, and bFGF-8 into NEUROBASAL media plus B27, BM MSCs were directed toward becoming early and mature NCs.

Adult↗

PubMed2005

Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMMSCs) are pluripotent cells capable of differentiating into several cell types and are thus an attractive cell source for connective tissue engineering. A challenge in such a use is expansion and directed seeding in vitro, requiring proliferation and survival, and directed migration, respectively, prior to functional differentiation. The epidermal growth factor (EGF) receptor (EGFR) is the prototypal growth factor receptor and elicits these responses from a wide variety of stromal, epithelial, and endothelial cells. Ligands for this receptor are appealing for use in tissue engineering because they are relatively resistant to biological extremes and amenable to high-volume production. Therefore, we determined whether an EGFR ligand, EGF, could be used for ex vivo expansion of BMMSCs. EGF stimulated motility in rat and immortalized human BMMSCs. EGF-induced proliferation was observed in immortalized human BMMSCs but was not apparent in rat BMMSCs under our experimental conditions. EGF did not, however, rescue either type of BMMSC from apoptosis due to lack of serum. During our examination of key signaling intermediaries, EGF caused robust phosphorylation of extracellular signal-regulated protein kinase (ERK) and protein kinase B/akt (AKT) but only minimal phosphorylation of EGFR and phospholipase C-gamma in rat BMMSCs, whereas in the human BMMSCs these intermediaries were all strongly activated. EGF also induced robust ERK activation in primary porcine mesenchymal stem cells. EGF pretreatment or cotreatment did not interfere with secondarily induced differentiation of either type of BMMSC into adipogenic or osteogenic lineages. Platelet-derived growth factor (PDGF) effects were similar to but not additive with those elicited by EGF, with some quantitative differences; however, PDGF did interfere with the differentiation of these BMMSCs. These findings suggest that EGFR ligands could be used for ex vivo expansion and direction of BMMSCs.

Animals↗

PubMed2006

Comparative characterization of hair follicle dermal stem cells and bone marrow mesenchymal stem cells.

We compared the growth and differentiation characteristics of hair follicle-derived dermal stem cells with bone marrow mesenchymal stem cells (MSCs). Follicular dermal cells were isolated from whisker hairs of Wistar rats and bone marrow MSCs were isolated from femora of the same animals. The adherent hair follicle dermal cells showed a fibroblastic morphology in serum-containing culture medium, were CD44(+), CD73(+), CD90(+), and CD34(), and had a population doubling time of 27 h. MSCs isolated from the bone marrow showed a similar morphology and population doubling time and expressed the same cell-surface markers. Following exposure to appropriate induction stimuli, both cell populations had the capacity to differentiate into various mesenchymal lineages, such as osteoblasts, adipocytes, chondrocytes, and myocytes and expressed neuroprogenitor cell markers. The rate and extent of differentiation were remarkably similar for both hair follicleand bone marrow-derived cells, whereas interfollicular dermal cells failed to differentiate. We identified telomerase activity in follicle dermal stem cells and marrow MSCs and demonstrated that they were capable of clonal expansion. In ex vivo analyses, we identified the presence of putative dermal stem cells in the dermal sheath and dermal papillae of the hair follicle. Consequently, the hair follicle may represent a suitable, accessible source for MSCs.

Animals↗

PubMed2005

Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells.

Like mesenchymal stem cells from bone marrow (BM-MSCs), adipose tissue-derived adult stem cells (ADAS cells) can differentiate into several lineages and present therapeutical potential for repairing damaged tissues. The use of allogenic stem cells can enlarge their therapeutical interest, provided that the grafted cells could be tolerated. We investigate here, for the first time, the immunosuppressive properties of ADAS cells compared with the well-characterized immunosuppressive properties of BM-MSCs. ADAS cells did not provoke in vitro alloreactivity of incompatible lymphocytes and, moreover, suppressed mixed lymphocyte reaction (MLR) and lymphocyte proliferative response to mitogens. The impairment of inhibition when ADAS cells and BM-MSCs were separated from lymphocytes by a permeable membrane suggests that cell contact is required for a full inhibitory effect. Hepatocyte growth factor is secreted by both stem cells but, similar to interleukin-10 and transforming growth factor-beta (TGF-beta), the levels of which were undetectable in supernatants of MLR inhibited by ADAS cells or BM-MSCs, it did not seem implicated in the stem cell suppressive effect. These findings support that ADAS cells share immunosuppressive properties with BM-MSCs. Therefore, ADAS cell-based reconstructive therapy could employ allogenic cells and because of their immunosuppressive properties, ADAS cells could be an alternative source to BM-MSCs to treat allogenic conflicts.

Adipose Tissue↗

PubMed2002

[Bone regeneration and Mesenchymal stem cells].

Bone marrow mesenchymal stem cells have been considered to differentiate into cells in bone, cartilage, tendon, muscle, and fat. Further analyses revealed that these cell also give rise to myocardial cells, oval cells and nerve cells, indicating high plasticity of these cells. Recent researches have been focused to utilize these cells to regenerate not only bone but also the life-maintaining major organs. As a cell source for the future regeneration of multiple organs, regeneration of the bone marrow is critical and thus studies on the process of bone marrow regeneration will benefit not only bone physiology field alone but also that of many other organs.

English Abstract↗

PubMed2005

Isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells.

Bone marrow mesenchymal stem cells (MSCs) are adult pluripotent cells that are considered to be an important resource for human cell-based therapies. Understanding the clinical potential of MSCs may require their use in preclinical large-animal models, such as pigs. The objectives of the present study were 1) to establish porcine MSC (pMSC) cultures; 2) to optimize in vitro pMSC culture conditions, 3) to investigate whether pMSCs are amenable to genetic manipulation, and 4) to determine pMSC reprogramming potential using somatic cell nuclear transfer (SCNT). The pMSCs isolated from bone marrow grew, attached to plastic with a fibroblast-like morphology, and expressed the mesenchymal surface marker THY1 but not the hematopoietic marker ITGAM. Furthermore, pMSCs underwent lipogenic, chondrogenic, and osteogenic differentiation when exposed to specific inducing conditions. The pMSCs grew well in a variety of media, and proliferative capacity was enhanced by culture under low oxygen atmosphere. Transient transduction of pMSCs and isogenic skin fibroblasts (SFs) with a human adenovirus carrying the gene for green fluorescent protein (GFP; Ad5-F35eGFP) resulted in more pMSCs expressing GFP compared with SFs. Cell lines with stable genetic modifications and extended expression of transgene were obtained when pMSCs were transfected with a plasmid containing the GFP gene. Infection of pMSC and SF cell lines by an adeno-associated virus resulted in approximately 12% transgenic cells, which formed transgenic clonal lines after propagation as single cells. The pMSCs can be expanded in vitro and used as nuclear donors to produce SCNT embryos. Thus, pMSCs are an attractive cell type for large-animal autologous and allogenic cell therapy models and for SCNT transgenesis.

Animals↗

PubMed2005

Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells.

The bone is the third most common site of cancer metastasis. To invade the bone, tumor cells produce osteoclast-activating factors that increase bone resorption by osteoclasts. Here we report that human neuroblastoma cells that form osteolytic lesions in vivo do not produce osteoclast-activating factors but rather stimulate osteoclast activity in the presence of human bone marrow mesenchymal stem cells. This alternative pathway of osteoclast activation involves a nonadhesive interaction between neuroblastoma cells and bone marrow mesenchymal stem cells. Stimulated bone marrow mesenchymal stem cells express markedly increased levels of interleukin-6, which is then responsible for osteoclast activation. This report describes a critical role of bone marrow mesenchymal stem cells in bone destruction in cancer.

Animals↗

PubMed2004

Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells.

Bone marrow mesenchymal stem cells (MSCs) can differentiate into a variety of cell types, including vascular smooth muscle cells (SMCs), and have tremendous potential as a cell source for cardiovascular regeneration. We postulate that specific vascular environmental factors will promote MSC differentiation into SMCs. However, the effects of the vascular mechanical environment on MSCs have not been characterized. Here we show that mechanical strain regulated the expression of SMC markers in MSCs. Cyclic equiaxial strain downregulated SM alpha-actin and SM-22alpha in MSCs on collagen- or elastin-coated membranes after 1 day, and decreased alpha-actin in stress fibers. In contrast, cyclic uniaxial strain transiently increased the expression of SM alpha-actin and SM-22alpha after 1 day, which subsequently returned to basal levels after the cells aligned in the direction perpendicular to the strain direction. In addition, uniaxial but not equiaxial strain induced a transient increase of collagen I expression. DNA microarray experiments showed that uniaxial strain increased SMC markers and regulated the expression of matrix molecules without significantly changing the expression of the differentiation markers (e.g., alkaline phosphatase and collagen II) of other cell types. Our results suggest that uniaxial strain, which better mimics the type of mechanical strain experienced by SMCs, may promote MSC differentiation into SMCs if cell orientation can be controlled. This study demonstrates the differential effects of equiaxial and uniaxial strain, advances our understanding of the mechanical regulation of stem cells, and provides a rational basis for engineering MSCs for vascular tissue engineering and regeneration.

Biomarkers↗

PubMed2003

[Advances of studies on mesenchymal stem cells].

Bone marrow mesenchymal stem cells (MSCs) are defined as pluripotent cells which have high self-renewal capacity and multipotentiality for differentiation. Because of their characteristics of supporting hematopoietisis, multipotentiality for differentiation and their possible use for both cell and gene engineerings, MSCs will have important value in clinic use.

Animals↗

PubMed2003

Isolation and identification of putative mesenchymal stem cells from bone marrow.

Mesenchymal stem cells are pluripotent progenitor cells found in bone marrow that have the capacity of differentiating into bone, cartilage, tendon, fat, muscle, and early progenitors of neural cells under certain conditions. It has also been shown that they support haematopoiesis in culture. We have successfully isolated mesenchymal stem cells from a bone marrow sample of an anaemic patient by using DMEM supplemented with 10% of FBS. They could be distinguished from other cells by their tendency to adhere to tissue culture plastic. The adherent time was about three to seven days. Microscopically, the cultured cells showed morphology resembling fibroblast and they divided actively. Early passage cultures were heterogenous and contained four morphologically distinct cell types; long spindle-shaped cells, star-shaped cells, petal-shaped cells and large flattened granular cells with vacuoles. Identification of mesenchymal stem cells was carried out by cytochemical analysis and immunophenotyping by flow cytometry. Identification of these cells is vital as they have properties that appear to make them ideal candidates for studying differentiation and make them suitable for cellular and gene therapy.

Biomarkers↗

PubMed2004

Lectins induce resistance to proteases and/or mechanical stimulus in all examined cells--including bone marrow mesenchymal stem cells--on various scaffolds.

Transplantation of bone marrow mesenchymal stem cells (MSC), chondrocytes, osteoblasts, or muscle cells promotes regeneration. However, these cells adhere poorly to some scaffolds--depending upon the scaffold material--and are often damaged by proteases or mechanical stimuli at site of transplantation. We found, however, that MSC, chondrocytes, and osteoblasts--along with some other cells--that were exposed to phaseolus vulgaris erythroagglutinin (PHA-E) or concanavalin A (ConA) increased their adhesion capacity on plastic tissue culture dishes and on plates of hydroxyapatite, titanium and poly-DL-lactic-co-glycolic acid (PLGA), and that these cells, moreover, built up resistance to proteases and/or mechanical stimuli. Thus, lectins may have great potential in tissue engineering and cell therapy.

Animals↗

PubMed2004

Direct cell contact influences bone marrow mesenchymal stem cell fate.

Adult bone marrow-derived mesenchymal stem cells (MSC) can differentiate into various cell types of mesenchymal origin, but mechanisms regulating such cellular changes are unclear. We have conducted co-culture experiments to examine whether mesenchymal stem cell differentiation is influenced by indirect or direct contact with differentiated cells. Cultured adult mesenchymal stem cells showed some characteristics of synthetic state vascular smooth muscle cells (SMC). When co-cultured with vascular endothelial cells (EC) without cell contact, they exhibited abundant well-organised smooth muscle alpha-actin (alpha-actin) filaments. Direct co-culture with endothelial cells resulted in increased smooth muscle alpha-actin mRNA and protein, yet also comprehensive disruption of smooth muscle alpha-actin filament organisation. In order to assess whether these cell contact effects on mesenchymal stem cells were cell type specific, we also analysed direct co-cultures of mesenchymal stem cells with dermal fibroblasts. However, these experiments were characterised by the appearance of abundant spindle-shaped myofibroblast-like cells containing organised smooth muscle alpha-actin filaments. Thus, direct contact with distinct differentiated cells may be a critical determinant of mesenchymal stem cell fate in blood vessels and other connective tissues.

Actin Cytoskeleton↗

PubMed2004

Isolation and multilineage differentiation of bovine bone marrow mesenchymal stem cells.

The bone marrow harbors a population of mesenchymal stem cells (MSCs) that possess the potential to differentiate into bone, cartilage, and fat, and along other tissue pathways. To date, MSCs from various species have been studied. Despite the bovine experimental model being widely used in experiments in vivo and in vitro, only a limited amount of information regarding bovine MSCs is available. The aim of this study was to isolate and induce the multilineage mesenchymal differentiation of bovine MSCs, thereby initiating further research on these cells. Bovine MSCs were isolated from eight calves, and osteogenic, chondrogenic, and adipogenic differentiation was induced by using a combination of previously reported protocols for other species. The level of differentiation was evaluated by histological examination and by analyzing the expression of tissue-specific genes by a quantitative "real time" reverse transcription/polymerase chain reaction technique. Following osteoinduction, the isolated fibroblast-like cells transformed into cuboidal cells and formed alkaline-phosphatase-positive colonies; during differentiation, these colonies transformed into mineralized nodules. In addition, osteogenesis was followed by osteocalcin and collagen type I mRNA expression. Chondrogenesis was confirmed by the demonstration of collagen type II, aggrecan, and sox9 mRNA expression in the cells stimulated by transforming growth factor beta1 in monolayer culture. After being cultured in an adipogenesis-inducing medium, the MSCs responded by the accumulation of lipid vacuoles and the expression of adipocyte-specific genes. We have therefore demonstrated that cells harvested from bovine bone marrow are capable of in vitro extensive multiplication and multilineage differentiation, making them a relevant and invaluable model in the field of stem cell research.

Adipocytes↗

PubMed2005

A comparative qualitative histological analysis of tissue-engineered bone using bone marrow mesenchymal stem cells, alveolar bone cells, and periosteal cells.

For tissue-engineered bone formation, autogenous osteogenic cells are of paramount importance for successful bone formation. In order to investigate the donor cell-related differences in tissue-engineered bone, cultured bone marrow mesenchymal stem cells, cultured alveolar bone cells, and cultured periosteal cells were examined for their in vivo potential to form bone. These cells were isolated from dogs, expanded in vitro, mixed with autologous fibrin glue and BMP-2, and then injected into the subcutaneous space on the dorsum of nude mice. Bone formation was evaluated at 12 weeks. Histomorphometric analysis demonstrated that the subcutaneous nodules formed in nude mice contained 26.9% newly formed bone when using the bone marrow mesenchymal stem cells, 41.1% newly formed bone when using the alveolar bone cells, and 58.2% newly formed bone when using the periosteal cells. The results suggest that periosteal cells are the best choice for enhancing bone formation in tissue engineering of bone regeneration.

Alveolar Process↗

PubMed2006

Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells.

The presence within bone marrow of a population of mesenchymal stem cells (MSCs) able to differentiate into a number of different mesenchymal tissues, including bone and cartilage, was first suggested by Friedenstein nearly 40 years ago. Since then MSCs have been demonstrated in a variety of fetal and adult tissues, including bone marrow, fetal blood and liver, cord blood, amniotic fluid and, in some circumstances, in adult peripheral blood. MSCs from all of these sources can be extensively expanded in vitro and when cultured under specific permissive conditions retain their ability to differentiate into multiple lineages including bone, cartilage, fat, muscle, nerve, glial and stromal cells. There has been great interest in these cells both because of their value as a model for studying the molecular basis of differentiation and because of their therapeutic potential for tissue repair and immune modulation. However, MSCs are a rare population in these tissues. Here we tried to identify cells with MSC-like potency in human placenta. We isolated adherent cells from trypsin-digested term placentas and examined these cells for morphology, surface markers, and differentiation potential and found that they expressed several stem cell markers. They also showed endothelial and neurogenic differentiation potentials under appropriate conditions. We suggest that placenta-derived cells have multilineage differentiation potential similar to MSCs in terms of morphology and cell-surface antigen expression. The placenta may prove to be a useful source of MSCs.

Adult↗

PubMed2004

Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow.

Mesenchymal stem cells (MSCs) are multipotent cells and can be induced in vitro and in vivo to differentiate not only into the variety of mesodermal cells, but into either ectodermal or endodermal cells. This capability indicates the usefulness of MSCs for tissue engineering. Cell surface antigen analyses using various types of CD antibodies demonstrated that adherent fibroblastic cells derived from fresh human bone marrow are mesenchymal types and the cells showed extensive capability for proliferation and/or differentiation. We labeled the adherent cultured marrow cells as MSCs and, significantly, found the MSCs could even proliferate from aged marrow cells. After about sixteen days of culturing, we were able to harvest 100 million MSCs from only 3 ml of fresh human marrow. Moreover, the MSCs could be cryopreserved at -80 degrees C without noticeable loss of viability and capability of osteoblastic differentiation. These results indicate that MSCs hold promise for utilization in hard tissue regeneration.

Bone Marrow Cells↗

PubMed2005

[Immunomodulation of bone marrow mesenchymal stem cells in hematopoietic stem cell transplantation--review].

Bone marrow mesenchymal stem cells (BM-MSC) have the characteristics of self-renewal and multipotency. They secrete a variety of cytokines and provided and ideal microenvironment for the division, proliferation and differentiation of hematopoietic stem cells (HSC) through the interaction with other stromal cells. Previous studies indicated that MSC could enhance engrafment and alleviate GVHD in allo-HSC and MSC co-transplantation. This effect on transplantation immunity may associate with escaping MHC compatible HSC from antigen recognition and suppressing activation and proliferation of nonspecific lymphocytes. In this paper, the characteristics of BM-MSC influencing transplantation immunity and its mechanism were reviewed.

Bone Marrow Cells↗