Placenta-derived multipotent stem cells
View Patent ↗Novel isolated stem cells derived from pre-term placental tissue and compositions comprising the stem cells are provided as well as use of the compositions for therapy, research and diagnosis. The cells and compositions are useful in treating Myelomeningocele (MCC), spina bifida (SB) or spinal cord injury or paralysis.
1. A method for treating one or more of: Myelomeningocele (MMC), spinal cord injury, or paralysis, in a subject in need thereof comprising administering to the subject an effective amount of a population of isolated pre-term chorionic villus (CV)-derived multipotent stem cells (C-mpSCs) expressing an elevated level of one or both of brain derived neurotropic factor (BDNF) or hepatocyte growth factor (HGF) as compared to adult bone marrow multipotent stem cells (BM-MSCs) and an intracellular marker comprising one or more of Nestin, Vimentin, Tuj1, S100β or neurofilament medium (NFM), or a culture conditioned media therefrom; and
wherein the elevated level of BDNF secreted by the population of C-mpSCs is at least two fold or higher compared to a concentration of BDNF secreted by BM-MSCs, and the elevated level of HGF secreted by the population of C-mpSCs is about three fold or higher compared to the concentration of HGF secreted by adult BM-MSCs.
2. The method of claim 1 , wherein the population of C-mpSCs or the culture conditioned media therefrom is administered in a pharmaceutically acceptable carrier or a biocompatible matrix.
3. The method of claim 1 , wherein the subject is a fetus and the composition is administered to the fetus in utero.
4. The method of claim 1 , wherein said population of C-mpSCs express one or both markers of CD56 + or CD271 + .
5. The method of claim 4 , wherein said population of C-mpSCs express one or more markers of CD105 + , CD90 + , CD73 + , CD44 + or CD29 + .
6. The method of claim 1 , wherein said population of C-mpSCs express the marker CD184 + .
7. The method of claim 1 , wherein said population of C-mpSCs express an integrin receptor comprising one or both of CD49d or CD49f.
8. The method of claim 1 , wherein said population of C-mpSCs express a transcriptional factor comprising one or more of Sox2, Sox10, Sox17 or Slug.
9. The method of claim 1 , wherein said population of C-mpSCs lack expression of one or more of endothelial markers or hematopoietic markers.
10. The method of claim 9 , wherein said marker is one or more of CD31, CD34 or CD45.
11. A method for treating a damaged neuron, comprising treating the neuron with an effective amount of a population of concentrated pre-term chorionic villus (CV)-derived multipotent stem cells (C-mpSCs) in a culture conditioned media derived from a population of isolated C-mpSCs expressing an elevated level of one or both of brain derived neurotropic factor (BDNF); or hepatocyte growth factor (HGF) as compared to adult bone marrow multipotent stem cells (BM-MSCs) and an intracellular marker comprising one or more of Nestin, Vimentin, Tuj1, S100β or neurofilament medium (NFM), for an effective amount of time; and
wherein the elevated level of BDNF secreted by the population of C-mpSCs is at least two fold or higher compared to a concentration of BDNF secreted by BM-MSCs, and the elevated level of HGF secreted by the population of C-mpSCs is about three fold or higher compared to the concentration of HGF secreted by adult BM-MSCs.
12. The method of claim 11 , wherein the neuron is an isolated cortical neuron or a spinal cord neuron.
13. The method of claim 11 , wherein the conditioned media is concentrated in an amount selected from the group of at least about 5 fold; at least about 10 fold; at least about 15 fold; at least about 20 fold; at least about 25 fold; at least about 30 fold; at least about 35 fold; at least about 40 fold; at least about 45 fold; at least about 50 fold; at least about 55 fold; at least about 60 fold; at least about 65 fold; at least about 70 fold; at least about 75 fold; at least about 80 fold; at least about 85 fold; and at least about 90 fold.
14. The method of claim 11 , wherein said treating is in vitro or in vivo.
15. The method of claim 11 , wherein the neuron to be treated is damaged by a neurodegenerative disease or disorder, an ischemic brain injury, a moderate or a catastrophic brain injury, a chemical neurotoxin exposure, a spinal cord injury, a traumatic brain injury, Parkinson's disease or a spinal cord contusion.
16. The method of claim 1 or 11 , wherein the population of C-mpSCs are isolated from a placental tissue during the first trimester or second trimester of a pregnancy.
17. The method of claim 1 or 11 , wherein the population of pre-term C-mpSCs are isolated from the pre-term placental tissue by the step of: dissecting and washing the pre-term placental tissue, culturing the dissected tissue in an adherent cell culture device with media containing fetal bovine serum (FBS), recombinant human basic fibroblast growth factor (bFGF), recombinant human epidermal growth factor (EGF), and harvesting the adherent cells for subsequent culture.
18. The method of claim 1 or 11 , wherein the population of C-mpSCs are isolated from the pre-term placental tissue by the step of: incubating dissected chorionic villus tissue in a solution comprising collagenase IV, mechanically dissociating the cells to generate a cell suspension, and centrifuging and harvesting the dissociated cells for subsequent culture in an adherent cell culture device with media containing fetal bovine serum (FBS), recombinant human basic fibroblast growth factor (bFGF), recombinant human epidermal growth factor (EGF).
19. The method of claim 1 or 11 , wherein the isolated C-mpSCs are prepared by a method comprising explant culture.
20. The method of claim 19 , wherein the method comprises explant culture of human preterm placental tissue.