Production of reprogrammed pluripotent cells
View Patent ↗The present invention provides a method of producing a reprogrammed cell, said method comprising exposing Stro-1 + multipotential cells and/or progeny cells thereof to one or more potency-determining factors under conditions sufficient to reprogram the cells. The present invention also provides cells produced by such a method and cells differentiated therefrom in addition to various uses of those cells.
1. A method of producing a cell having increased stem cell potency, said method comprising exposing a population of human cells enriched for Stro-1 positive mesenchymal precursor cells (MPCs) to factors that increase stem cell potency under conditions sufficient to reprogram the cells, wherein the factors comprise OCT4, SOX2, KLF4 and cMYC or nucleic acids encoding the factors, and wherein the population of human cells enriched for Stro-1 positive MPCs is derived from adipose tissue or dental pulp tissue.
2. The method according to claim 1 additionally comprising culturing the exposed population to produce cells having increased stem cell potency.
3. The method according to claim 1 additionally comprising isolating the cells having increased stem cell potency.
4. The method according to claim 1 , comprising culturing the exposed population to obtain cells having broader differentiation potential than the Stro-1 positive MPCs.
5. The method according to claim 1 , wherein the population is obtained from a post-natal human.
6. The method according to claim 1 , wherein exposing the population to the factors comprises introducing the one or more nucleic acids comprising sequences encoding the factors operably linked to a promoter into the Stro-1 positive MPCs.
7. The method according to claim 6 , comprising administering a plurality of nucleic acids each comprising a sequence encoding a distinct factor operably linked to a promoter.
8. The method according to claim 6 , wherein the nucleic acid(s) are within one or more vector(s).
9. The method according to claim 8 , wherein the vector(s) is (are) a viral vector(s).
10. The method according to claim 6 , wherein the nucleic acid(s) do(es) not integrate into the genome of the Stro-1 positive MPCs.
11. The method according to claim 1 , wherein the cells having increased stem cell potency are pluripotent.
12. The method according to claim 1 , wherein the cells having increased stem cell potency (i) express a cell market selected from the group consisting of Oct-4, Nanog, SSEA3, SSEA4, Tra-1-60 and Tra-1-81; (ii) exhibit morphology characteristic of pluripotent cells; and/or (iii) form teratomas when introduced into an immunocompromised animal.
13. The method of claim 1 additionally comprising administering a cell or population of cells produced by performing the method of claim 1 or a cell or population of cells differentiated thereform to a subject in need thereof.
14. The method of claim 1 additionally comprising screen for compounds useful in the treatment or prevention of a disease of disorder by exposing the cell produced by performing the method of claim 1 to said compounds.
15. the method according to claim 1 , wherein nanog is not one of the factors exposed to the Stro-1positive MPCs.
16. The method according to claim 15 , wherein the factors consist of OCT4, SOX2, KLF4, and cMYC.
17. The method according to claim 1 , wherein the Stro-1positive MPCs are Stro-1 bright MPCs.