Methods of enhancing fibroblast therapeutic activity

Abstract

Disclosed are compositions of matter, cells, protocols and procedures useful for augmentation of one or more therapeutic activities of fibroblast cellular populations. In one embodiment fibroblasts are pretreated with growth factor-comprising composition(s), wherein the growth factor(s) may be cytokines, peptides, and/or proteins. In another embodiment fibroblasts are cultured with platelet rich plasma and/or derivatives from platelet rich plasma. In another embodiment, fibroblasts are cultured under hypoxic conditions prior to administration to an individual. The disclosure further provides means of assessment of fibroblast activity in vitro, including wound repair assay and cytokine production, for example.

1 . A method of augmenting efficacy of fibroblasts for regeneration of cells and/or tissues, comprising the steps of contacting fibroblasts with one or more biologically active substances; and/or culturing the fibroblasts under conditions to enhance efficacy of said fibroblast for regeneration. 
     
     
         2 . The method of  claim 1 , wherein said biologically active substance comprises one or more cytokines. 
     
     
         3 . The method of  claim 2 , wherein said cytokine comprises one or more growth factors. 
     
     
         4 . The method of  claim 3 , wherein said growth factor is FGF-alpha. 
     
     
         5 . The method of  claim 3 , wherein said growth factor is FGF-beta. 
     
     
         6 . The method of  claim 3 , wherein said growth factor is a member of the TGF-beta family. 
     
     
         7 . The method of  claim 1 , wherein said biologically active substance comprises platelet rich plasma. 
     
     
         8 . The method of  claim 1 , wherein said regeneration comprises immune modulation. 
     
     
         9 . The method of  claim 1 , wherein said regeneration comprises angiogenesis. 
     
     
         10 . The method of  claim 1 , wherein said regeneration is regeneration of spinal discs. 
     
     
         11 . The method of  claim 1 , wherein the fibroblast cells are selected from the group consisting of (a) fibroblasts obtained by biopsy, cultured and proliferated; (b) subsets thereof having greater ability to differentiate; and (c) a combination thereof. 
     
     
         12 . The method of  claim 1 , wherein the fibroblasts express stage specific embryonic antigen 3 (SSEA3). 
     
     
         13 . The method of  claim 1 , wherein said fibroblasts are comprised in a pharmaceutically acceptable carrier selected from the group consisting of sterile solutions, hydrogels, implantable cell matrices, devices and a combination thereof. 
     
     
         14 . The method of  claim 1 , wherein the fibroblasts are derived from tissues comprising skin, heart, blood vessels, bone marrow, skeletal muscle, liver, pancreas, brain, adipose tissue, foreskin, placental, and/or umbilical cord. 
     
     
         15 . The method of  claim 1 , wherein the fibroblasts are placental, fetal, neonatal, adult or a combination thereof.