Tissue-specific differentiation matrices and uses thereof

Abstract

In some aspects, this invention provides a method of making a bone marrow-derived tissue-specific stem cell proliferation, expansion, isolation and rejuvenation extracellular matrix. In other aspects, this invention provides a method of making a tissue-specific fibroblast-derived stem cell differentiation extracellular matrix. Also provided are methods of using such a cell-derived preservation or differentiation matrices to induce tissue-specific differentiation of pluripotent cells, repair damaged tissue, and treat a subject having a physiologic deficiency using the same.

1 . A method of repairing damaged tissue comprising:
 a) inducing tissue-specific differentiation of isolated stem cells into a differentiated cell type comprising:
 i) generating a first differentiation factor comprising a differentiation-inducing extracellular matrix by culturing fibroblast cells on a surface; and 
 ii) contacting the isolated stem cells with the first differentiation factor, thereby inducing the stem cells to differentiate into the differentiated cell type, 
 wherein the damaged tissue and differentiated cell type are of the same tissue type as the fibroblast cells, wherein the fibroblast cells have been removed from the differentiation-inducing extracellular matrix before contacting the isolated stem cells with the differentiation-inducing extracellular matrix, and wherein the damaged tissue, fibroblast cells, and differentiated cells are all from one of the following tissue types: neural tissue, epidermal tissue, dermal tissue, adipose tissue, cardiac tissue, kidney tissue, muscle tissue, liver tissue, cartilage tissue, pancreas tissue, tissue of the endometrium of uterus, umbilical cord tissue, or dental pulp tissue; 
   b) isolating the differentiated cells from the first differentiation factor; and   c) administering the differentiated cells to a subject to produce a therapeutic effect or repair of the damaged tissue.   
     
     
         2 . The method of  claim 1 , wherein the differentiated cell type is a neuron, epithelial cell, dermal cell, adipocyte, cardiomyocyte, renal cell, myocyte, hepatocyte, chondrocyte, islet cell, endothelial cell, or dental pulp cell. 
     
     
         3 . The method of  claim 1 , wherein the fibroblast cells are human or mouse fibroblast cells. 
     
     
         4 . The method of  claim 1 , wherein the isolated stem cells are from bone marrow, periosteum, trabecular bone, adipose tissue, synovium, skeletal muscle, deciduous teeth, fetal pancreas, lung, liver, amniotic fluid, umbilical cord blood and umbilical cord tissues. 
     
     
         5 . The method of  claim 1 , wherein the isolated stem cells are naturally occurring stem cells or are engineered stem cells. 
     
     
         6 . The method of  claim 1 , wherein the isolated stem cells are embryonic stem cells, mesenchymal stem cells or induced pluripotent stem cells. 
     
     
         7 . The method of  claim 6 , wherein the isolated stem cells are mesenchymal stem cells (MSCs) and are obtained by a method comprising:
 i) contacting a MSC-containing sample with a cell-derived preservation matrix generated by human bone marrow cells; and   ii) isolating the MSCs from the cell-derived preservation extracellular matrix.   
     
     
         8 . The method of  claim 7 , further comprising:
 iii) expanding the isolated MSCs on a cell-derived preservation extracellular matrix generated by human bone marrow cells.   
     
     
         9 . The method of  claim 7 , wherein the MSC-containing sample is from bone marrow, periosteum, trabecular bone, adipose tissue, synovium, skeletal muscle, deciduous teeth, fetal pancreas, lung, liver, amniotic fluid, umbilical cord blood and umbilical cord tissues. 
     
     
         10 . The method of  claim 1 , wherein the differentiation-inducing extracellular matrix is a 3D matrix. 
     
     
         11 . The method of  claim 1 , wherein the differentiation-inducing extracellular matrix is free of feeder cells. 
     
     
         12 . The method of  claim 1 , wherein the differentiation-inducing extracellular matrix is free of fibroblast cells. 
     
     
         13 . The method of  claim 1 , wherein the surface is a surface of a cell culture dish or plate. 
     
     
         14 . The method of  claim 1 , wherein the method further comprises contacting the differentiated cell type cells with a second differentiation factor. 
     
     
         15 . The method of  claim 14 , wherein the differentiated cell type cells are cardiomyocytes and the second differentiation factor is bFGF and azacytidine.