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Mesenchymal Progenitor Cells (mesenchymal + progenitor_cell)
Selected AbstractsIn vitro multipotentiality and characterization of human unfractured traumatic hemarthrosis-derived progenitor cells: A potential cell source for tissue repairJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Sang Yang Lee Mesenchymal progenitor cells (MPCs) are a very attractive tool in the context of repair and regeneration of musculoskeletal tissue damaged by trauma. The most common source of MPCs to date has been the bone marrow, but aspirating bone marrow from the patient is an invasive procedure. In an attempt to search for alternative sources of MPCs that could be obtained with minimal invasion, we looked into traumatic hemarthrosis of the knee. In this study, we determined whether a population of multipotent MPCs could be isolated from acute traumatic knee hemarthrosis in the absence of intra-articular fractures. Mononuclear cells were isolated from the aspirated hemarthrosis by density gradient separation, and cultured. We were able to obtain plastic adherent fibroblast-like cells from the mononuclear cell fractions. Flow cytometry analysis revealed that the adherent fibroblast-like cells were consistently positive for CD29, CD44, CD105, and CD166, and were negative for CD14, CD34, and CD45. These were similar to control bone marrow stromal cells. These cells could differentiate in vitro into osteogenic, adipogenic, and chondrogenic cells in the presence of lineage-specific induction factors. In conclusion, acute unfractured traumatic hemarthrosis of the knee contains MPCs with multipotentiality. Because knee hemarthrosis is easy to harvest with minimal pain and without unnecessary invasion, we regard hemarthrosis-derived cells as an additional progenitor cell source for future tissue engineering and cell-based therapy in knee injuries. J. Cell. Physiol. 210: 561,566, 2007. © 2006 Wiley-Liss, Inc. [source] Primary mouse embryonic fibroblasts: A model of mesenchymal cartilage formation,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2004Christopher J. Lengner Cartilage formation is an intricate process that requires temporal and spatial organization of regulatory factors in order for a mesenchymal progenitor cell to differentiate through the distinct stages of chondrogenesis. Gene function during this process has best been studied by analysis of in vivo cartilage formation in genetically altered mouse models. Mouse embryonic fibroblasts (MEFs) isolated from such mouse models have been widely used for the study of growth control and DNA damage response. Here, we address the potential of MEFs to undergo chondrogenic differentiation. We demonstrate for the first time that MEFs can enter and complete the program of chondrogenic differentiation ex vivo, from undifferentiated progenitor cells to mature, hypertrophic chondrocytes. We show that chondrogenic differentiation can be induced by cell,cell contact or BMP-2 treatment, while in combination, these conditions synergistically enhance chondrocyte differentiation resulting in the formation of 3-dimensional (3-D) cartilaginous tissue ex vivo. Temporal expression profiles of pro-chondrogenic transcription factors Bapx1 and Sox9 and cartilaginous extracellular matrix (ECM) proteins Collagen Type II and X (Coll II and Coll X) demonstrate that the in vivo progression of chondrocyte maturation is recapitulated in the MEF model system. Our findings establish the MEF as a powerful tool for the generation of cartilaginous tissue ex vivo and for the study of gene function during chondrogenesis. © 2004 Wiley-Liss, Inc. [source] To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGFJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2004Jörg Fiedler Abstract The recruitment of mesenchymal progenitor cells (MPCs) and their subsequent differentiation to osteoblasts is mandatory for bone development, remodeling, and repair. To study the possible involvement of platelet-derived growth factor (PDGF) isoforms, primary human MPCs and osteogenic differentiated progenitor cells (dOB) were examined for chemotaxic response to homodimeric human platelet-derived growth factor AA, -BB, and heterodimeric PDGF-AB. The role of PDGF receptors was addressed by preincubation with PDGF receptor alpha and beta chain specific antibodies. Migration of MPCs, dOB, and primary osteoblasts (OB) was stimulated by the addition of rhPDGF-AA, rhPDGF-BB, and rhPDGF-AB. The effect was highest in MPCs and for rhPDGF-BB, and declining with osteogenic differentiation. Preincubation with the receptor alpha specific antibody decreased the CI to borderline values while pretreatment with the receptor beta specific antibody led to a complete loss of chemotactic response to PDGF isoforms. In control experiments, basal migration values and rhBMP-2 as well as rxBMP-4 induced chemotaxis of MPC were not influenced by the addition of receptor alpha or beta antibodies. Interestingly, without preincubation the parallel exposure of MPC to rhTGF-,1 instantaneously leads to a selective loss of migratory stimulation by rhPDGF-AA. The chemotactic effect of PDGF isoforms for primary human MPCs and the influence of osteogenic differentiation suggest a functional role for recruitment of MPCs during bone development and remodeling. Moreover, these observations may be useful for novel approaches towards guided tissue regeneration or tissue engineering of bone. © 2004 Wiley-Liss, Inc. [source] Alterations in the temporal expression and function of cadherin-7 inhibit cell migration and condensation during chondrogenesis of chick limb mesenchymal cells in vitroJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2009Dongkyun Kim Endochondral bone formation requires a complex interplay among immature mesenchymal progenitor cells to form the cartilaginous anlagen, which involves migration, aggregation and condensation. Even though condensation of chondrogenic progenitors is an essential step in this process, its mechanism(s) has not been well studied. Here, we show that cadherin-7 plays a central role in cellular condensation by modulating cell motility and migration. In this study, many mesenchymal cells failed to migrate, and precartilage condensation was inhibited, after knockdown of endogenous cadherin-7 levels. Exposure of mesenchymal cells to SB203580 (a specific inhibitor of p38MAPK), LiCl (an inhibitor of GSK-3,) or overexpression of ,-catenin resulted in inhibition of cadherin-7 levels and, subsequently, suppression of cell migration. Collectively, our results suggest that cadherin-7 controls cell migration in chick limb bud mesenchymal cells, and that p38MAPK and GSK signals are responsible for regulating cadherin-7-mediated cell migration. J. Cell. Physiol. 221: 161,170, 2009. © 2009 Wiley-Liss, Inc [source] Putative heterotopic ossification progenitor cells derived from traumatized muscle,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2009Wesley M. Jackson Abstract Heterotopic ossification (HO) is a frequent complication following combat-related trauma, but the pathogenesis of traumatic HO is poorly understood. Building on our recent identification of mesenchymal progenitor cells (MPCs) in traumatically injured muscle, the goal of this study was to evaluate the osteogenic potential of the MPCs in order to assess the role of these cells in HO formation. Compared to bone marrow-derived mesenchymal stem cells (MSCs), a well-characterized population of osteoprogenitor cells, the MPCs exhibited several significant differences during osteogenic differentiation and in the expression of genes related to osteogenesis. Upon osteogenic induction, MPCs showed increased alkaline phosphatase activity, production of a mineralized matrix, and up-regulated expression of the osteoblast-associated genes CBFA1 and alkaline phosphatase. However, MPCs did not appear to reach terminal differentiation as the expression of osteocalcin was not substantially up-regulated. With the exception of a few genes, the osteogenic gene expression profile of traumatized muscle-derived MPCs was comparable to that of the MSCs after osteogenic induction. These findings indicate that traumatized muscle-derived MPCs have the potential to function as osteoprogenitor cells when exposed to the appropriate biochemical environment and are the putative osteoprogenitor cells that initiate ectopic bone formation in HO. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1645,1651, 2009 [source] Multilineage mesenchymal differentiation potential of human trabecular bone-derived cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2002Ulrich Nöth Abstract Explant cultures of adult human trabecular bone fragments give rise to osteoblastic cells, that are known to express osteoblast-related genes and mineralize extracellular matrix. These osteoblastic cells have also been shown to undergo adipogenesis in vitro and chondrogenesis in vivo. Here we report the in vitro developmental potential of adult human osteoblastic cells (hOB) derived from explant cultures of collagenase-pretreated trabecular bone fragments. In addition to osteogenic and adipogenic differentiation, these cells are capable of chondrogenic differentiation in vitro in a manner similar to adult human bone marrow-derived mesenchymal progenitor cells. High-density pellet cultures of hOB maintained in chemically defined serum-free medium, supplemented with transforming growth factor-,1, were composed of morphologically distinct, chondrocyte-like cells expressing mRNA transcripts of collagen types II, IX and X, and aggrecan. The cells within the high-density pellet cultures were surrounded by a sulfated prote-oglycan-rich extracellular matrix that immunostained for collagen type II and proteoglycan link protein. Osteogenic differentiation of hOB was verified by an increased number of alkaline phosphatase-positive cells, that expressed osteoblast-related transcripts such as alkaline phosphatase, collagen type I, osteopontin and osteocalcin, and formed mineralized matrix in monolayer cultures treated with ascorbate, ,-glycerophosphate, and bone morphogenetic protein-2. Adipogenic differentiation of hOB was determined by the appearance of intracellular lipid droplets, and expression of adipocyte-specific genes, such as lipoprotein lipase and peroxisome proliferator-activated receptor ,2, in monolayer cultures treated with dexamethasone, indomethacin, insulin and 3-isobutyl-l-methylxanthine. Taken together, these results show that cells derived from collagenase-treated adult human trabecular bone fragments have the potential to differentiate into multiple mesenchymal lineages in vitro, indicating their developmental plasticity and suggesting their mesenchymal progenitor nature. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] The Effects of Ethanol Consumption on Vasculogenesis Potential in Nonhuman PrimatesALCOHOLISM, Issue 1 2008J. Koudy Williams Background:, Vasculogenesis is essential to the preservation and repair of damaged or diseased vessels. Alcohol is the most commonly abused drug among young adults, but its effects on vessel growth and repair are unknown. The basis of vascular repair is endothelial progenitor cell (EPC) recruitment to assist in the formation of new vascular network (vasculogenesis). Therefore, the objective of this study was to measure the effects of ethanol consumption on the production, mobilization and vasculogenesis potential EPCs in nonhuman primates. Methods:, Four to five year-old (young adult) male rhesus monkeys consumed monkey chow and water (Control, n = 7), or chow and water + ethanol (Alcohol, 2.45 g/d, n = 7) for 12 months. Peripheral blood (PB) and bone marrow (BM) samples were collected for fluorescence-activated cell-sorting analysis of cell surface antigens (CD45, CD31, CD44, CD133, VEGF-R2 , or KDR); and for capillary formation on Matrigel-coated plates. Results:, There were greater numbers of nonhematopoeitic stromal cells (CD45,) and putative mesenchymal progenitor cells (CD45,/CD44+) in the PB and BM of Alcohol versus Control monkeys (p < 0.05). Additionally, there were greater numbers of EPCs (CD45,/CD133+/KDR+) in the BM and PB of Alcohol versus Control monkeys (p < 0.05). However, the EPCs of Alcohol monkeys were less likely to form capillaries on matrigel-coated plates than Control monkeys (p < 0.05). Conclusions:, Ethanol consumption in monkeys markedly increased the production and mobilization of EPCs, but decreased their ability to form capillaries. The pathophysiologic consequences of such effects are unclear, but may represent an ethanol-induced chronic stress on the BM, resulting in EPC. [source] Regeneration of large bone defects in sheep using bone marrow stromal cellsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 5 2008P. Giannoni Abstract Bone repair was addressed in a critical-sized defect model in sheep, combining a ceramic biomaterial and mesenchymal progenitor cells. The defects in the tibial mid-diaphysis were treated with autologous bone or with a silicon-stabilized tricalcium phosphate biomaterial, implemented or not by the addition of expanded bone marrow stromal cells. An internal locking compression plate and an external fixator were applied for stabilization. Radiographies were taken during the 8 months follow-up: the pixel grey levels of the lesion areas were determined to evaluate the repair process radiologically. Microradiography, histology and vascular density tests were performed. The autologous bone-treated group performed best, as assessed radiologically, within 20,24 weeks after surgery. Very limited healing was detected in the other experimental group: a partial bone deposition occurred at the periphery of the bony stumps only in the cell-seeded scaffolds. Interestingly, this effect ended within 20,24 weeks, as for the autologous bone, suggesting similar kinetics of the repair processes involved. Moreover, bone deposition was located where a significant reduction of the ceramic scaffold was detected. Faxitron microradiography and histology data confirmed these results. Vascular density analysis evidenced that cell-seeded scaffolds supported an increased vascular ingrowth. Thus, the interactions with the proper microenvironment and the oxygen and nutrient supply in the inner part of the constructs seem fundamental to initiate scaffold substitution and to improve cell performance in tissue-engineered approaches to bone repair. Copyright © 2008 John Wiley & Sons, Ltd. [source] Plasticity of clonal populations of dedifferentiated adult human articular chondrocytesARTHRITIS & RHEUMATISM, Issue 5 2003Andrea Barbero Objective To investigate whether adult human articular chondrocytes (AHACs), dedifferentiated by monolayer expansion, can differentiate toward diverse mesenchymal lineages and, if so, whether this ability is regulated by growth factors during monolayer expansion. Methods AHACs were expanded as multiclonal or clonal populations in medium without (control) or with factors enhancing cell dedifferentiation (transforming growth factor ,1, fibroblast growth factor 2, and platelet-derived growth factor type BB [TFP]). Cells were then cultured under conditions promoting chondrogenic, osteogenic, or adipogenic differentiation, and the acquired phenotypes were assessed histologically, biochemically, and by real-time reverse transcriptase,polymerase chain reaction. Results Multiclonal populations of both control- and TFP-expanded AHACs differentiated toward the chondrogenic, osteogenic, and adipogenic lineages. Compared with control-expanded AHACs, TFP-expanded cells displayed enhanced chondrogenic differentiation capacity (2.4-fold higher glycosaminoglycan/DNA content and 2,500-fold higher up-regulation of type II collagen) and osteogenic differentiation capacity (9.4-fold higher increase in alkaline phosphatase activity and 12.4-fold higher up-regulation of bone sialoprotein), but reduced formation of adipocytes (5.2-fold lower oil red O,positive cells/area). Clonal populations of AHACs could be efficiently expanded in TFP, but not in control medium. Most TFP-expanded clones were able to redifferentiate only into chondrocytes (7 of 20) or were unable to differentiate (6 of 20). However, some clones (2 of 20) differentiated toward all of the lineages investigated, thus displaying characteristics of mesenchymal progenitor cells. Conclusion Dedifferentiated AHACs exhibit differentiation plasticity, which is modulated by growth factors used during monolayer expansion and is highly heterogeneous across different clones. Clonal culture of AHACs in the presence of regulatory molecules could lead to the identification of AHAC subpopulations with enhanced cartilage repair capacity. [source] | |||||||||||||