Compositions for proliferation of cells and related methods
AssigneeThe Hospital for Sick Children
InventorsFreda D. MILLER, David KAPLAN, Kristen SMITH, Maryline PARIS, Sibel NASKA
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Abstract
We have discovered that p63 inhibition results in increased cellular proliferation. We have also performed a screen for agents capable of increasing cellular proliferation, (e.g., of stem cells such as skin-derived precursors (SKPs)). The invention therefore invention provides compositions, methods, and kits for increasing proliferation of cells, using compounds that decrease p63 expression or activity or using the compounds described herein. The invention also features methods of using these compounds for increasing hair growth, improving skin health, or promoting skin repair in a subject.
Claims20
A method of increasing proliferation of a cell, said method comprising contacting said cell with a sufficient amount of one or more of:
- (a) a compound that decreases p63 expression or activity, or
- (b) a compound selected from the group consisting of acyclovir, alprostadil, aristolochic acid, carbadox, chlorpyrifos, cyclocreatine, 7,4′-dimethoxyisoflavone, dorzolamide, S(−)eticlopride, evoxine, guaifenesin, hydroxyprogesterone, kaempferol, linamarin, mexicanolide, MG 624, pramoxine, tannic acid, targinine, alpha-methyllycacontine, mecamylamine hexamethonium, alsterpaullone, and yohimbic acid, or an analog thereof, under conditions that support cell proliferation.
A composition comprising:
- (a) an isolated stem cell;
- and
- (b) one or more compounds that decrease p63 expression or activity and/or one or more compounds selected from the group consisting of acyclovir, alprostadil, aristolochic acid, carbadox, chlorpyrifos, cyclocreatine, 7,4′-dimethoxyisoflavone, dorzolamide, S(−) eticlopride, evoxine, guaifenesin, hydroxyprogesterone, kaempferol, linamarin, mexicanolide, MG 624, pramoxine, tannic acid, targinine, alpha-methyllycacontine, mecamylamine hexamethonium, alsterpaullone, and yohimbic acid, or an analog thereof, wherein said compound is present in an amount sufficient to promote proliferation of said stem cell.
A composition comprising:
- (a) one or more compounds that decrease p63 expression or activity and/or one or more compounds selected from the group consisting of acyclovir, alprostadil, aristolochic acid, carbadox, chlorpyrifos, cyclocreatine, 7,4′-dimethoxyisoflavone, dorzolamide, S(−)eticlopride, evoxine, guaifenesin, hydroxyprogesterone, kaempferol, linamarin, mexicanolide, MG 624, pramoxine, tannic acid, targinine, alpha-methyllycacontine, mecamylamine hexamethonium, alsterpaullone, and yohimbic acid, or an analog thereof;
- and
- (b) a carrier suitable for topical administration.
A method of increasing SKP proliferation in a subject, promoting hair growth, repairing skin, or improving skin health in a subject, said method comprising administering a sufficient amount of:
- (a) one or more compounds that inhibit p63 expression or activity;
- and/or
- (b) one or more compounds selected from the group consisting of acyclovir, alprostadil, aristolochic acid, carbadox, chlorpyrifos, cyclocreatine, 7,4′-dimethoxyisoflavone, dorzolamide, S(−)eticlopride, evoxine, guaifenesin, hydroxyprogesterone, kaempferol, linamarin, mexicanolide, MG 624, pramoxine, tannic acid, targinine, alpha-methyllycacontine, mecamylamine hexamethonium, alsterpaullone, and yohimbic acid, or an analog thereof.
A method of identifying a compound capable of altering cell proliferation, said method comprising:
- (a) contacting a SKP with a candidate compound;
- and
- (b) determining the proliferation rate of said SKP, wherein an alteration in the proliferation rate of said SKP in the presence of said compound as compared to in the absence of said compound, indicates that said compound alters the rate of cell proliferation.
Dependencies are inferred from the claim text.