Tailoring the Secretion of Biological Factors
OwnerAdam J. Mellott, Jacob G. Hodge +3inventors
InventorsAdam J. Mellott, Jacob G. Hodge, Heather Decker, Jennifer L. Robinson, David S. Zamierowski
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Abstract
Methods of externally reprogramming how cells behave and which biological factors are secreted from cells, such as by introducing an external (controllable) stimuli for obtaining a desired outcome for producing a target biological factor, are provided.
Claims4
A method of characterizing a therapeutically desirable constituent or constituent profile of a secretome composition secreted from a cell type of interest, comprising:
- (i) seeding a first tissue mimetic three-dimensional (3D) hydrogel block (TMHB) comprising a macrostructure defined by a continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material with a first cell type of interest;
- (ii) simulating in vitro cell growth and propagation of the first cell type of interest by feeding the first cell type of interest with a first culture media and allowing the first cell type of interest to propagate throughout the first TMHB and to secrete the secretome composition;
- (iv) collecting a secretome composition;
- (v) subjecting the secretome composition to a stratification operation based on molecular weight cut-off values providing a plurality of different strata each characterized by a different range of constituent-molecular weights;
- (vi) characterizing and/or identifying one or more individual constituents present with each strata of interest;
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- (v) testing each strata of interest for relative therapeutic benefit either by in vivo analysis or ex vivo analysis and identifying the strata of interest that provides a highest therapeutic benefit as the therapeutically constituent profile.
A method of tailoring a constituent profile of a natural secretome composition secreted from a cell type of interest, comprising:
- (i) seeding a first tissue mimetic three-dimensional (3D) hydrogel block (TMHB) comprising a macrostructure defined by a continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material with a first cell type of interest;
- (ii) feeding first cell type of interest with a first culture media;
- (iii) introducing at least one external stimuli configured to modify the natural secretome composition secreted from a cell type of interest to more closely track a target secretome composition having a target constituent or target constituent profile;
- wherein the at least one external stimuli comprises one or more controllable parameters, such as addition of a coating on an interface between the continuous polymeric matrix material and the network of microporous channels and/or chambers, adjusting an oxygen concentration, a pH, a temperature, and fluid dynamics through the first TMHB;
- (iv) allowing the first cell type of interest to propagate throughout the first TMHB and to secrete the secretome composition;
- (iv) collecting a modified secretome composition that is different than the natural secretome composition due to the external stimuli.
Dependencies are inferred from the claim text.