MULTIPOTENT STEM CELLS AND USES THEREOF
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 tissue regenerative formulation comprising:
a population of stem cells that express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD13, CD44, CD45, CD90, and CD105;
and a pharmaceutically acceptable carrier.
2 . The formulation of claim 1 , further comprising a cellular differentiating agent.
3 . The formulation of claim 2 , wherein the cellular differentiating agent is a chondrogenic agent.
4 . The formulation of claim 3 , wherein the chondrogenic agent is a corticosteroid, a cytokine or a growth factor.
5 . The formulation of claim 4 , wherein the chondrogenic agent is selected from the group consisting of: dexamethasone, TGF-beta and BMPs.
6 . The formulation of claim 2 , wherein the cellular differentiating agent is a tenocyte inducing agent.
7 . The formulation of claim 6 , wherein the tenocyte inducing agent is a BMP.
8 . The formulation of claim 2 , wherein the cellular differentiating agent is an osteoinductive agent.
9 . The formulation of claim 8 , wherein the cellular osteoinductive agent is a BMP.
10 . The formulation of claim 2 , wherein the cellular differentiating agent is an endothelial cell-inductive agent.
11 . The formulation of claim 10 , wherein the endothelial cell-inductive agent is a growth factor.
12 . The formulation of claim 2 , wherein the population of stem cells is committed to differentiate.
13 . The formulation of claim 1 , further comprising at least one subpopulation of differentiated progeny cells.
14 . The formulation of claim 1 , further comprising at least one subpopulation of differentiated immune cells.
15 . The formulation of claim 1 , further comprising an extracellular matrix component.
16 . The formulation of claim 1 , wherein the population of stem cells further comprise a subpopulation of stem cells having a transgene that expresses a polypeptide or oligonucleotide.
17 . The formulation of claim 1 , wherein the population of stem cells is autologous with respect to an intended recipient of the formulation.
18 . The formulation of claim 1 , wherein the population of stem cells is allogeneic with respect to an intended recipient of the formulation.