Enhanced placental stem cells and uses thereof
Provided herein are placental stem cells that exhibit increased survival (“enhanced placental stem cells”), compositions comprising such placental stem cells, and methods of using such placental stem cells and compositions.
1. An isolated placental stem cell, wherein said placental stem cell has been modified to comprise or express miR-29a, and wherein said placental stem cell demonstrates increased survival relative to corresponding unmodified placental stem cells when cultured under one or more conditions that cause cell death.
2. The isolated placental stem cell of claim 1 , wherein said placental stem cell expresses at least one survival-associated gene at a decreased level as compared to the expression of the same survival-associated gene in a corresponding unmodified placental stem cell.
3. The isolated placental stem cell of claim 2 , wherein said survival-associated gene is ADAMTS9, BACE1, BCL2, CAV2, CD276, CDC42, CDK6, COL3A1, COL4A1, COL4A2, CPEB3, TRIM63, CXXC6/TET1, DIABLO, DNMT3A, DNMT3B, FGA, IMPDH1, INSIG1, KREMEN2, LPL, MCL1, PIK3R1, PPM1D, SPARC.
4. The isolated placental stem cell of claim 1 , wherein said miR-29a causes said placental cell to express Cyclin D3 and/or Cyclin E at an increased level as compared to a corresponding unmodified placental stem cell.
5. The isolated placental stem cell of claim 1 , wherein said placental stem cell exhibits (i) decreased expression of caspase 3/7, (ii) increased mitochondrial membrane potential, and/or (iii) increased metabolic activity when cultured under one or more conditions that cause cell death as compared to corresponding unmodified placental stem cells cultured under the same condition(s).
6. An isolated population of cells, wherein at least 50% of the cells in said population are the cells of claim 1 .
7. The isolated population of cells of claim 6 , wherein at least 80% of the cells in said population of cells are the cells of claim 1 .
8. The population of cells of claim 6 , wherein said placental stem cells in said population are CD10 + , CD34 − , CD105 + , CD200 + placental stem cells.
9. A composition comprising the isolated placental stem cell of claim 1 .
10. The placental stem cell of claim 1 , wherein said placental stem cell is a CD10 + , CD34 − , CD105 + , CD200 + placental stem cell.
11. The composition of claim 1 , wherein said placental stem cells are CD10 + , CD34 − , CD105 + , CD200 + placental stem cells.
12. A method of producing placental stem cells that comprise or express miR-29a, wherein said placental stem cells demonstrate increased survival relative to corresponding unmodified placental stem cells when cultured under one or more conditions that cause cell death, said method comprising contacting a population of placental stem cells with an effective amount of miR-29a, such that said placental stem cells, after having been contacted with said miR-29a express Cyclin D3 and/or Cyclin E at an increased level as compared to a corresponding number of unmodified placental stem cells not contacted with said miR-29a.
13. An isolated placental stem cell or population thereof produced by the method of claim 12 .
14. A composition comprising an isolated placental stem cell produced by the method of claim 12 .
15. The method of claim 12 , wherein said placental stem cells are CD10 + , CD34 − , CD105 + , CD200 + placental stem cells.