Biomedical subjects

P Conget

Publications and source records attributed to P Conget.

7 recordsLinked to original sources

PubMed2001

Mesenchymal stem cells.

Within the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal stem or mesenchymal progenitor cells. These cells can be ex vivo expanded and induced, either in vitro or in vivo, to terminally differentiate into osteoblasts, chondrocytes, adipocytes, tenocytes, myotubes, neural cells, and hematopoietic-supporting stroma. The multipotential of these cells, their easy isolation and culture, as well as their high ex vivo expansive potential make these cells an attractive therapeutic tool. In this work we will review the information dealing with the biology of mesenchymal progenitors as it has been revealed mainly by ex vivo studies performed with bone marrow-derived cells. The discussed topics include, among others, characteristics of mesenchymal progenitors, evidence for the existence of a vast repertoire of uncommitted and committed progenitors both in the bone marrow and in mesenchymal tissues, a diagram for their proliferative hierarchy, and comments on mobilization, microenvironment, and clinical use of mesenchymal progenitors. Despite the enormous data available at molecular and cellular levels, it is evident that a number of fundamental questions still need to be resolved before mesenchymal progenitors can be used for safe and effective clinical applications in the context of both cell and gene therapies.

Animals↗

PubMed2000

Mesenchymal progenitor cells in human umbilical cord blood.

Haemopoiesis is sustained by two main cellular components, the haematopoietic cells (HSCs) and the mesenchymal progenitor cells (MPCs). MPCs are multipotent and are the precursors for marrow stroma, bone, cartilage, muscle and connective tissues. Although the presence of HSCs in umbilical cord blood (UCB) is well known, that of MPCs has been not fully evaluated. In this study, we examined the ability of UCB harvests to generate in culture cells with characteristics of MPCs. Results showed that UCB-derived mononuclear cells, when set in culture, gave rise to adherent cells, which exhibited either an osteoclast- or a mesenchymal-like phenotype. Cells with the osteoclast phenotype were multinucleated, expressed TRAP activity and antigens CD45 and CD51/CD61. In turn, cells with the mesenchymal phenotype displayed a fibroblast-like morphology and expressed several MPC-related antigens (SH2, SH3, SH4, ASMA, MAB 1470, CD13, CD29 and CD49e). Our results suggest that preterm, as compared with term, cord blood is richer in mesenchymal progenitors, similar to haematopoietic progenitors.

Adipocytes↗

PubMed2000

Biology and clinical utilization of mesenchymal progenitor cells.

Within the complex cellular arrangement found in the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal progenitor cells (MPC). These cells can be expanded ex vivo and induced, either in vitro or in vivo, to terminally differentiate into at least seven types of cells: osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes and hematopoietic-supporting stroma. This broad multipotentiality, the feasibility to obtain MPC from bone marrow, cord and peripheral blood and their transplantability support the impact that the use of MPC will have in clinical settings. However, a number of fundamental questions about the cellular and molecular biology of MPC still need to be resolved before these cells can be used for safe and effective cell and gene therapies intended to replace, repair or enhance the physiological function of the mesenchymal and/or hematopoietic systems.

Animals↗

PubMed1995

Structure-antioxidative activity relationships in benzylisoquinoline alkaloids.

The antioxidative properties of the aporphines boldine, glaucine and apomorphine, and of the benzyltetrahydroisoquinolines (+/-)-coclaurine and (+/-)-norarmepavine were compared in the brain homogenate autoxidation model. The IC50 values found lay in the 16-20 microM range for the aporphines and were 131.7 microM, and 79.3 microM for coclaurine and norarmepavine, respectively. These results indicate that the antioxidative capacity (AC) of these compounds is related to the presence of the biphenyl system rather than phenol groups. The non-phenolic glaucine inhibited the 2,2'-azobis-(2-amidinopropane)(AAP)-induced inactivation of lysozyme with an IC50 value of 12 microM, while the corresponding values for the phenolic coclaurine and norarmepavine were 10 and 20 microM, respectively. N-Methylation of glaucine to its quaternary ammonium reduced its protective effect by two-thirds. This result suggests that a benzylic hydrogen neighbouring a nitrogen lone electron pair may be the key to the protective effect of non-phenolic aporphines.

Animals↗

PubMed1995

IL-3 increases surface proteoglycan synthesis in haemopoietic progenitors and their adhesiveness to the heparin-binding domain of fibronectin.

Haemopoietic progenitor cells (HPC) synthesize and accumulate a single type of membrane-associated chondroitin sulphate proteoglycan (MA-PG), which participates in HPC adhesiveness to fibronectin by interacting with its heparin-binding domain. Shortly after incubating cells with IL-3, we observed an increase in MA-PG synthesis in the multipotent (FDCP-mix) but not in the bipotent (FDCP-1) progenitor cell line. The charge density, hydrodynamic size, nature of the glycosaminoglycan (GAG) chains and stability of MA-PG from IL-3-treated and non-treated FDCP-mix cells were the same, suggesting that IL-3 affects the amount of MA-PG. The latter was evaluated by flow cytometry using monoclonal antibodies to the core protein and GAG residues. In all cases the mean fluorescence intensities were higher for IL-3-treated than for untreated cells. Cell adhesion studies to dishes coated with the fibronectin 40 kD fragment, containing the heparin-binding domain, demonstrated that adhesiveness of IL-3-treated cells was higher than that of untreated cells. These results suggest that in multipotent haemopoietic cells IL-3 regulates the amount of membrane-associated proteoglycans, which in turn modify the adhesive interactions of cells with the heparin-binding domain of fibronectin.

Animals↗

PubMed1995

The sulfation degree of membrane-associated proteoglycan from a hemopoietic cell line is determined by changes in the growth state of the cell.

Multipotential hemopoietic progenitor cells (FDCP-mix) proliferate in culture medium supplemented with horse serum. When transferred to a medium without serum, cells do not proliferate and enter a quiescent state. Both proliferative and quiescent cells synthesize only chondroitin sulfate proteoglycan (CS-PG) which is associated to the cell membrane. Incorporation of 35SO4 into CS-PG was 4-fold higher in quiescent than in proliferative cells. Flow cytometric studies using monoclonal antibodies which recognize the core protein or the CS chains, showed that the increased uptake of sulfate was not the consequence of an increase in the abundance of CS-PG. Further characterization demonstrated that CS-PG isolated from quiescent cells exhibited a slightly higher hydrodynamic size than CS-PG from proliferative cells. However, the glycosaminoglycan chains from PG derived from proliferative and quiescent cells have the same hydrodynamic size. Through ion-exchange chromatography we observed that the mean charge density of PG from quiescent cells was higher than in proliferative cells, suggesting a higher sulfation degree from PG synthesized by quiescent cells. This was confirmed by flow cytometric studies using monoclonal antibody 2B6, which recognizes the unsaturated terminal disaccharide of chondroitin-4-O-sulfate.

Animals↗

PubMed1994

Modifications in the synthesis of membrane-associated chondroitin sulfate proteoglycans in hemopoietic progenitor cells are accompanied by alterations in their adhesive properties.

In vitro studies in our laboratory have indicated that murine hemopoietic progenitor cell (HPC) lines, irrespective of their differentiation stage, synthesize and accumulate in the cell membrane a unique species of chondroitin sulfate proteoglycan (CS-PG). It has been postulated that CS-PG participates in HPC adhesion to pericellular stromal fibronectin by interacting with its heparin-promoting binding region. To further support this contention, we first attempted to modify CS-PG synthesis in HPC by the use of chlorate and p-nitrophenyl beta-D-xyloside, which inhibit sulfation and glycosaminoglycan (GAG) addition in proteoglycans, respectively. We then studied the effect that these modifications may have in the adhesive capacity of HPC to interact with fibronectin and its cell- and heparin-promoting binding chymotryptic fragments. Treatment with chlorate which resulted in a decreased sulfation of membrane-associated 35 S-labeled CS-PG, as judged by ion exchange chromatography, did not affect HPC adhesion to fibronectin or its fragments. However, beta-xyloside treatment which reduces the abundance of membrane-associated CS-PG, as evidenced by molecular sieve chromatography, produced a major and specific decrease in HPC adhesion to the heparin-promoting binding fragment of fibronectin. These results indicate that CS-PG are involved in HPC interaction with fibronectin, in a mode that seems to be dependent on the differentiation stage of HPC.

Animals↗