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 method for promoting wound healing in a subject, said method comprising administering to a human subject an effective dose of a formulation comprising:
(i) a population of stem cells that express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD44, CD45, and CD90, and
(ii) a pharmaceutically acceptable carrier,
in an amount sufficient to promote or improve the healing of said wound.
2. A method for promoting wound healing in a subject, said method comprising administering a formulation comprising:
(i) a population of stem cells that express a stem cell transcription factor but do not detectably express MHC Class I or cell surface CD44, CD45, and CD90,
(ii) at least one subpopulation of differentiated progeny cells, and
(iii) a pharmaceutically acceptable carrier,
in an amount sufficient to promote or improve the healing of said wound.
3. A method for promoting tissue generation in a subject, said method comprising transplanting into a subject at a surgical site a formulation comprising:
(i) a population of stem cells that express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD44, CD45, and CD90, and
(ii) a pharmaceutically acceptable carrier,
wherein the population of stem cells engrafts to target tissue, reduces inflammation in the target tissue and differentiates in vivo to match the tissue type and supplement the target tissue, thereby promoting tissue generation in the subject.
4. The method of claim 3 , where the surgical site is the site of a joint procedure.
5. The method of claim 4 , where the surgical site is the site of repair of articular cartilage.
6. The method of claim 5 , wherein transplanting is by implanting or injecting the formulation into a patient's injured cartilage tissue.
7. The method of claim 3 , where the surgical site is the site of a cosmetic procedure.
8. A method for promoting tissue generation in a subject, said method comprising transplanting into a subject at a surgical site a formulation comprising:
(i) a population of stem cells that express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD44, CD45, and CD90,
(ii) a cellular differentiating agent, and
(iii) a pharmaceutically acceptable carrier,
wherein the population of stem cells engrafts to target tissue, reduces inflammation in the target tissue and differentiates in vivo to match the tissue type and supplement the target tissue, thereby promoting tissue generation in the subject.
9. The method of claim 8 , where the surgical site is the site of an orthopedic, bone or cosmetic procedure.
10. The method of claim 1 , wherein the stem cells do not detectably express CD13 or CD105.
11. The method of claim 2 , wherein the stem cells do not detectably express CD13 or CD105.
12. The method of claim 3 , wherein the stem cells do not detectably express CD13 or CD105.
13. The method of claim 8 , wherein the stem cells do not detectably express CD13 or CD105.