Tissue Engineering Methods and Compositions

Abstract

A composition for use in the treatment of osteoarthritis in a subject includes an adipose-derived stem cell and an effective amount of a biologically active agent. The composition also includes a pharmaceutically acceptable carrier or excipient. The biologically activate agent is a BMP-6 polypeptide or a functional fragment thereof. The treatment includes exposing the ADS cell to an effective amount of said biologically active agent. The effective amount of the biologically active agent is sufficient to induce the adipose-derived stem cell to differentiate into a cell capable of treating the osteoarthritis in the subject upon administration of the composition to the subject.

What is claimed is: 
     
         1 . A composition for use in the treatment of osteoarthritis in a subject, the composition comprising:
 an adipose-derived stem cell and an effective amount of a biologically active agent; and   a pharmaceutically acceptable carrier or excipient, wherein:   the biologically activate agent is a BMP-6 polypeptide or a functional fragment thereof,   the adipose-derived stem cell is exposed to the effective amount of said biologically active agent, and   the effective amount of the biologically active agent is sufficient to induce the adipose-derived stem cell to differentiate into a cell capable of treating the osteoarthritis in the subject upon administration of the composition to the subject.   
     
     
         2 . The composition of  claim 1 , further comprising:
 a scaffold comprising a biocompatible material,   wherein the adipose-derived stem cell is disposed on or in the scaffold.   
     
     
         3 . The composition of  claim 1 , wherein:
 the biologically active agent is disposed on or in a scaffold in such a way as to allow controlled release of the biologically active agent over time.   
     
     
         4 . The composition of  claim 2 , wherein:
 the biocompatible material comprises a material selected from the group consisting of: an absorbable material, a non-absorbable material, and combinations thereof.   
     
     
         5 . The composition of  claim 4 , wherein the biocompatible material comprises a non-absorbable material selected from the group consisting of: a polytetrafluoroethylene (PTFE), an expanded PTFE (ePTFE), a polyamide, a nylon, a polysulfone, a cellulosic, an acrylic, tantalum, polyvinyl alcohol, carbon, ceramic, a metal, an acrylic, a polycarbonate, a polyester, a polyether, a poly(ether ketone), a poly(ether ether ketone), a poly(aryl ether ketone), a poly(ether ether ketone ether ketone), a poly(ethylene terephthalate), a poly(methyl (meth)acrylate), a polyolefin, a polysulfone, a polyurethane, a polyethylene, a polypropylene, a poly(vinyl chloride), a carbon fiber reinforced composite, a glass fiber reinforced composite, and combinations thereof. 
     
     
         6 . The composition of  claim 4 , wherein the biocompatible material comprises an absorbable material selected from the group consisting of: a polyglycolic acid (PGA), a polylactic acid (PLA), a polyglycolidelactide, a polycaprolactone, a polydioxanone, a polyoxalate, a polyanhydride, a poly(phosphoester), catgut suture, collagen, silk, alginate, agarose, chitin, chitosan, hydroxyapatite, bioabsorbable calcium phosphate, hyaluronic acid, elastin, a polyorthoester, a poly(amino acid), a pluronic/F-12, a poly(ethylene oxide)/poly(ethylene glycol) (PEO/PEG), gelatin, a blood derivative, plasma, synovial fluid, serum, fibrin, a proteoglycan, and combinations thereof. 
     
     
         7 . The composition of  claim 1 , wherein the effective amount of BMP-6 is in a range from approximately 1 picomole/mL to approximately 10 millimoles/mL. 
     
     
         8 . The composition of  claim 1 , wherein:
 the composition is configured to be administered to a target tissue selected from the group consisting of: articular cartilage, growth plate cartilage, meniscus, labrum, intervertebral disc, tendon, ligament, periodontal ligament, fascia, and muscle, and   the target tissue comprises multiple tissue types that are integrated with one another selected from the group consisting of: bone and cartilage, muscle and tendon, and ligament and bone.   
     
     
         9 . The composition of  claim 1 , wherein the adipose-derived stem cells are cells that have been isolated from an adipose depot selected from the group consisting of subcutaneous abdomen, thigh, buttocks, infrapatellar fat pad, and combinations thereof. 
     
     
         10 . The composition of  claim 1 , wherein the adipose-derived stem cell is selected from the group consisting of: adipose-derived stem cells autologous to the subject, adipose-derived stem cells allogeneic to the subject, adipose-derived stem cells xenogeneic to the subject, and combinations thereof. 
     
     
         11 . The composition of  claim 9 , wherein:
 the isolated adipose-derived stem cells have been transfected or transduced with an expression construct encoding at least one of BMP-6 polypeptide, a BMP-6 receptor polypeptide, or a functional fragment thereof, and   the expression construct comprises a regulatable promoter operatively linked to at least one coding sequence encoding the biologically active agent or at least one of the BMP-6 polypeptide, the BMP-6 receptor polypeptide, or the functional fragment thereof.   
     
     
         12 . The composition of  claim 1 , wherein in addition to the differentiated cell, an expression vector encoding the biologically active agent or a BMP-6 polypeptide or a functional fragment thereof is administered to the subject. 
     
     
         13 . The composition of  claim 12 , wherein the expression vector is selected from the group consisting of: a viral vector, an adenovirus vector, an adeno-associated virus vector, a plasmid, and a deoxyribonucleic acid molecule. 
     
     
         14 . The composition of  claim 1 , wherein:
 the adipose-derived stem cell has been exposed in culture to at least one other growth factor or cytokine, and   the at least one other growth factor or cytokine is selected from the group consisting of: another TGF-6 superfamily member, an IGF-1, an FGF, an EGF, a PDGF, a parathyroid hormone related peptide (PTHrP), an interleukin, and combinations thereof.   
     
     
         15 . The composition of  claim 1 , wherein:
 along with the adipose-derived stem cell, another cell type other than the adipose-derived stem cell is administered to the subject,   the another type of cell is selected from the group consisting of: a chondrocyte, a fibroblast, an osteoblast, a myoblast, a neuron, a progenitor cell, and combinations thereof, and   human embryonic stem cells are excluded.   
     
     
         16 . The composition of  claim 15 , wherein:
 the adipose-derived stem cell and the another cell has been exposed in culture to at least one other growth factor or cytokine in addition to the BMP-6 polypeptide or the functional fragment thereof.   
     
     
         17 . The composition of  claim 1 , wherein:
 differentiated adipose-derived stem cells are selected based on:
 expression of at least one cell surface marker selected from the group consisting of: CD10, CD13, CD31, CD34, CD36, CD44, CD49, CD54, CD55, CD59, CD65, CD105, and CD166, 
 differential expression of aldehyde dehydrogenase (ALDH), 
 differential expression of collagen I, 
 differential expression of collagen II, 
 efflux of a dye or nucleic acid label, 
 telomere length or the expression of telomerase, 
 expression of BMP-6, 
 expression of a BMP-6 receptor polypeptide, 
 expression of other members of the TGF-β superfamily or receptors thereof, or 
 combinations of any of the forgoing. 
   
     
     
         18 . The composition of  claim 17 , wherein:
 the differentiated adipose-derived stem cells are selected based on efflux of the dye, and   the dye comprises Hoechst 33342.   
     
     
         19 . The composition of  claim 17 , wherein the differentiated adipose-derived stem cells are selected by repeated passage in culture.