ABSTRACT
The in vitro generation of hematopoietic stem cells (HSCs) and mature hematopoietic cells from hemangioblast derived from embryonic stem (ES) or induced pluripotent stem (iPS) cells promises to provide an alternative source of cells that could replace total bone marrow cells or HSC-enriched fractions. This mini-review deals with innovation related to hemangioblast-based methods for blood cells production as disclosed in recent patent literature and current barriers to clinical translation are discussed.
Subject(s)
Embryonic Stem Cells/cytology , Hemangioblasts/transplantation , Induced Pluripotent Stem Cells/cytology , Humans , Patents as TopicABSTRACT
In order to better understand the mechanism of destabilization of liposomes used as drug carriers for oral administration by bile salts, the insertion and partition of sodium taurocholate (TC) into small unilamellar vesicles (SUV) and multilayers (ML) of dipalmitoylphosphatidylcholine (DPPC) were examined by continuous turbidity analysis and DSC. Optical density was recorded during the progressive solubilisation of DPPC SUV and ML into DPPC/TC mixed micelles by varying the rate of TC addition and the temperature. The results show that the insertion and diffusion of TC in the DPPC membrane is a slow process influenced by the polymorphism of the lipid, independently of its organisation. This dynamic study mimics physiological phenomena of the digestion of liposomes. In the gastrointestinal tract, DPPC SUV would be more resistant to TC than egg phosphatidylcholine (EPC) SUV [K. Andrieux, L. Forte, S. Lesieur, M. Paternostre, M. Ollivon, C. Grabielle-Madelmont, Insertion and partition of sodium taurocholate into egg phosphatidylcholine vesicles, Pharm. Res. 21 (2004) 1505-1516] because of the lower insertion of TC into DPPC bilayer at 37 degrees C at low TC concentration in the medium (fasted conditions). At high TC concentration (postprandially or after lipid absorption), the use of DPPC to prepare liposomes will delay or reduce the liberation of a drug encapsulated into liposomes in the gastrointestinal tract. As a conclusion, the addition of DPPC appears an attractive strategy to formulate orally administered liposomes.
Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Drug Carriers/chemistry , Gastrointestinal Tract/metabolism , Taurocholic Acid/metabolism , 1,2-Dipalmitoylphosphatidylcholine/metabolism , Administration, Oral , Calorimetry, Differential Scanning , Crystallization , Drug Carriers/metabolism , Liposomes , Models, Biological , Nephelometry and Turbidimetry , Phosphatidylcholines/chemistry , Postprandial Period , Solubility , TemperatureABSTRACT
PURPOSE: To get a continuous description of the insertion and partition processes of sodium taurocholate (TC) into the lipid bilayers of vesicles that can serve as a model for understanding the mechanism of destabilization by the bile salts of liposomes used as drug carriers for oral administration. METHODS: The progressive solubilization of egg phosphatidylcholine vesicles during TC addition at controlled rates was followed by continuous turbidity (OD) and resonance energy transfer (RET) between two fluorescent probes. The influence of the lipid and TC concentrations as well as the rate of TC addition on the processes were examined. RESULTS: Continuous turbidity recordings allowed following of the size and composition evolutions of the mixed TC/lipid aggregates formed at different steps of the vesicle-micelle transition. The solubilization mechanism is governed by complex kinetics that depend on the surfactant concentration and its addition rate. A two-step process characterizes the evolution of the vesicular state: interaction of TC molecules with the external monolayer of the vesicles first occurs. The homogeneous distribution of TC within the lipid matrix after its insertion is a very slow process. A micellar structural reorganization is observed when TC is added rapidly. CONCLUSIONS: This work provides detailed information on the slow insertion and diffusion kinetics of TC in liposomal bilayers by using a dynamic study which mimics physiological phenomena of digestion.
Subject(s)
Detergents/chemistry , Liposomes/chemistry , Phosphatidic Acids/chemistry , Phosphatidylcholines/chemistry , Taurocholic Acid/chemistry , Micelles , Nephelometry and Turbidimetry , Solubility , Spectrometry, FluorescenceABSTRACT
Studies on hematopoiesis have focused on the function and composition of human bone marrow stroma. Stroma function gives hematopoietic stem cells the microenvironment appropriate for self-renewal and/or prompt differentiation into hematopoietic progenitor cells, then into terminal specialized cells. Human bone marrow stroma has been dissected into hematopoietic and nonhematopoietic components. The former includes hematopoietic-derived cells, mainly macrophages, while the latter, still poorly characterized, is composed mainly of endothelial and mesenchymal stem cells and their derivatives (adipocytes, chondrocytes, cells of the osteogenic lineage). Isolation of bone marrow mesenchymal stem cells has made available a population of adherent cells, belonging to the non-hematopoietic stroma, which are morphologically and phenotypically homogeneous. This review will focus on: (i) definition of bone marrow stroma and mesenchymal stem cells; (ii) methods of mesenchymal stem cell isolation, morphological and phenotypic characterization; (iii) mesenchymal stem cell functional and differentiation properties and (iv) therapeutic applications of mesenchymal stem cells.
