Multipotent stem cells and uses thereof

Abstract

The invention provides a quiescent stem cell having the capacity to differentiate into ectoderm, mesoderm and endoderm, and which does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. The invention further provides a proliferative stem cell, which expresses genes including Oct-4, Nanog, Sox2, GDF3, P16INK4, BMI, Notch, HDAC4, TERT, Rex-1 and TWIST but does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. The cells of the invention can be isolated from adult mammals, have embryonic cell characteristics, and can form embryoid bodies. Methods for obtaining the stem cells, as well as methods of treating diseases and the differentiated stem cells, are also provided.

1 . A method of enhancing recovery from joint surgery, comprising administering to the joint during surgery to repair the joint a composition comprising stem or progenitor cells in an amount effective to enhance recovery, and a pharmaceutically acceptable carrier. 
     
     
         2 . The method of  claim 1 , wherein the stem cells express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD13, CD44, CD45, CD90, and CD105. 
     
     
         3 . The method of  claim 2 , wherein the stem cells are capable of proliferating and differentiating into ectoderm, mesoderm and endoderm. 
     
     
         4 . The method of  claim 2 , wherein the stem cells are synovial fluid derived, blood derived or tissue derived. 
     
     
         5 . The method of  claim 2 , wherein the stem cells are isolated from a mammal. 
     
     
         6 . The method of  claim 4 , wherein the stem cell is isolated from a human. 
     
     
         7 . The method of  claim 4 , wherein the stem cells are isolated from an adult mammal. 
     
     
         8 . The method of  claim 1 , wherein the stem cells are autologous with respect to a recipient undergoing the joint surgery. 
     
     
         9 . The method of  claim 1 , wherein the stem cells are allogeneic with respect to a recipient undergoing the joint surgery. 
     
     
         10 . The method of  claim 1 , wherein the stem cells are committed to differentiate. 
     
     
         11 . The method of  claim 1 , wherein the composition further comprises at least one subpopulation of differentiated progeny cells. 
     
     
         12 . The method of  claim 11 , further comprising at least one subpopulation of differentiated immune cells. 
     
     
         13 . A method of differentiating a stem or progenitor cell, the method comprising: culturing a stem or progenitor cell that expresses a stem cell transcription factor but does not detectably express MHC Class I or cell surface markers CD13, CD44, CD45 and CD90, under conditions to form a desired cell type, thereby differentiating the stem or progenitor cell. 
     
     
         14 . The method of  claim 13 , wherein the stem or progenitor cell is synovial fluid derived, blood derived or tissue derived. 
     
     
         15 . The method of  claim 13 , wherein the stem or progenitor cell is differentiated into a cell lineage of a germ layer selected from the group consisting of ectoderm, mesoderm and endoderm, and/or a specific cell type selected from the group consisting of: a neural, glial, chondroblast, osteoblast, adipocyte, hepatocyte, a smooth muscle cell, a skeletal muscle cell, cardiac cell, pancreatic cell, pulmonary cell, and endothelial cell. 
     
     
         16 . The method of  claim 15 , wherein the stem or progenitor cell is differentiated into a chondroblast. 
     
     
         17 . The method of  claim 16 , wherein the stem or progenitor cell are cultured under conditions for forming a chondroblast comprising culturing with at least one growth factor selected from the group consisting of: EGF, PDGF, TGF-β1, BMP-2, BMP-12, BMP-13, and BMP-4. 
     
     
         18 . The method of  claim 16 , further comprising a step of confirming chondroblast differentiation. 
     
     
         19 . The method of  claim 18 , wherein the step of confirming chondroblast differentiation quantitative reverse-transcription-polymerase chain reaction (Q-RT-PCR) for collagen type II and aggrecan transcripts and/or staining with Alcian Blue to demonstrate cartilage matrix production. 
     
     
         20 . The method of  claim 1 , wherein the stem or progenitor cell expresses at least one of Oct-4, Nanog, Sox-2, KLF4, c-Myc, Rex-1, GDF-3, LIF receptor, and Stella. 
     
     
         21 . The method of  claim 13 , wherein the stem or progenitor cell expresses at least one of Oct-4, Nanog, Sox-2, KLF4, c-Myc, Rex-1, GDF-3, LIF receptor, and Stella.