Enhanced reconstitution and autoreconstitution of the hematopoietic compartment
The present disclosure relates to the acceleration of hematopoietic compartment reconstitution in a subject in need of hematopoietic stem cell transplantation by administering a composition having a protein transduction domain-MYC (PTD-MYC) fusion protein in combination with hematopoietic stem cell transplantation and to the enhancement of hematopoietic compartment autoreconstitution in a subject in need thereof by administering a composition having a protein transduction domain-MYC (PTD-MYC) fusion protein.
1. A method of preparing a population of hematopoietic stem cells for transplantation in a subject in need thereof, comprising:
(a) contacting a population of hematopoietic stem cells with a composition comprising a MYC-composition, a Bcl-2-composition, or both, for less than 1 day, wherein the MYC-composition and the Bcl-2-composition each comprise a protein transduction domain (PTD); and
(b) washing the hematopoietic stem cells following step (a) prior to administering the hematopoietic stem cells to a subject.
2. The method of claim 1 , wherein the population of hematopoietic stem cells is contacted with the composition comprising the MYC-composition, the Bcl-2-composition, or both, for about 1 hour.
3. The method of claim 1 , wherein the population of hematopoietic stem cells is washed about 1 minute to about 1 hour, about 4 hours, about 6 hours, about 8 hours, about 12 hours, or about 24 hours prior to administering the hematopoietic stem cells to the subject.
4. The method of claim 1 , wherein the population of hematopoietic stem cells is washed with a saline solution.
5. The method of claim 1 , wherein the population of hematopoietic stem cells is treated with the MYC-composition.
6. The method of claim 1 , wherein the population of hematopoietic stem cells is treated with the composition comprising the MYC-composition and the Bcl-2-composition.
7. The method of claim 1 , wherein the Bcl-2-composition is a PTD-Bcl-2 fusion protein.
8. The method of claim 7 , wherein the Bcl-2-composition is a TAT-Bcl-2 fusion protein.
9. The method of claim 1 , wherein the MYC-composition is a PTD-MYC fusion protein.
10. The method of claim 9 , wherein the MYC-composition is a TAT-MYC fusion protein.
11. The method of claim 1 , wherein the population of hematopoietic stem cells is obtained from bone marrow, peripheral blood cells, peripheral blood cells that have undergone apheresis, peripheral blood cells that have undergone leukapheresis, umbilical cord blood, or amniotic fluid.
12. The method of claim 1 , wherein the population of hematopoietic stem cells is obtained from bone marrow, peripheral blood, umbilical cord blood, or amniotic fluid of the subject.
13. The method of claim 1 , wherein the population of hematopoietic stem cells is obtained from bone marrow, peripheral blood, umbilical cord blood, or amniotic fluid of an allogenic donor.
14. The method of claim 1 , wherein the subject is a human or non-human animal.