Métodos para generar células madre hematopoyéticas funcionales

• Main Authors: SHAH, Dhvanit I, DALEY, George Q
• Format: Patent
• Language: Spanish
• Published: 23.10.2023
• Subjects: AGRICULTURE; ANIMAL HUSBANDRY; BEER; BIOCHEMISTRY; CARE OF BIRDS, FISHES, INSECTS; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FISHING; FORESTRY; HUMAN NECESSITIES; HUNTING; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; NEW BREEDS OF ANIMALS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; TRAPPING; VINEGAR; WINE

Se describen métodos para preparar poblaciones de células madre hematopoyéticas (HSC), por ejemplo, HSC autólogas y/o alogénicas, usando estiramiento mecánico o agonistas del miembro 4 vanilloide de la subfamilia del canal catiónico potencial del receptor transitorio (Trpv4), y métodos de uso de las HSC en trasplante. proporcionó. Específicamente, los métodos comprenden proporcionar una población de células que comprende células endoteliales (HE) hemogénicas, poner en contacto las células HE con una cantidad de un agonista de Trpv4; y/o someter las células a un estiramiento bidimensional cíclico, durante un tiempo y en condiciones suficientes para estimular la transición endotelial a HSC. Además se describen métodos para tratar trastornos hematológicos, metabólicos o inmunes malignos o no malignos que comprenden administrar a un sujeto una cantidad terapéuticamente eficaz de HSC obtenidas mediante los métodos. (Traducción automática con Google Translate, sin valor legal) Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.