Compositions comprising stem cells expressing mesenchymal and neuronal markers and uses thereof to treat neurological disease
The invention provides pharmaceutical compositions comprising human immature dental pulp stem cells (hIDPSCs) wherein the hIDPSCs express CD44 and CD13. The invention also provides methods of treating a neurological disease or condition comprising systemically administering to a subject a pharmaceutical composition comprising hIDPSCs wherein the hIDPSCs express CD44 and CD13. For example, for treating neurological diseases or conditions including supporting the neuro-protective mechanism in subjects diagnosed with early HD or repairing lost DA neurons in subjects diagnosed with PD.
1. A cryopreserved pharmaceutical composition comprising undifferentiated human immature dental pulp stem cells (hIDPSCs),
wherein at least 80% of the hIDPSCs express DARPP32 and BDNF;
at least 90% of the hIDPSCs express CD44 and CD13; and
the hIDPSCs maintain the capacity to form multiple cell types including neuronal cells, fibroblast cells, and perivascular cells.
2. The pharmaceutical composition of claim 1 , wherein expression of CD44 and CD13 enables the hIDPSCs to cross the blood brain barrier (BBB).
3. The pharmaceutical composition of claim 1 , wherein the hIDPSCs express dopamine receptor D2.
4. The pharmaceutical composition of claim 1 , wherein the hIDPSCs maintain colony forming capacity after multiple passages.
5. The pharmaceutical composition of claim 1 formulated for intravenous (IV) injection.
6. The pharmaceutical composition of claim 1 , wherein the hIDPSCs are cryopreserved with dimethyl sulfoxide (DMSO).
7. A method of treating a neurological disease or condition comprising systemically administering to a subject the cryopreserved pharmaceutical composition of claim 1 .
8. The method of claim 7 , wherein the hIDPSCs are cryopreserved with DMSO.
9. The method of claim 7 , wherein the pharmaceutical composition is intravenously administered to the subject.
10. The method of claim 7 , wherein the hIDPSCs are autologous and/or allogeneic to the subject.
11. The method of claim 7 , wherein the neurological disease or condition is selected from the group consisting of Parkinson's disease (PD), multiple sclerosis, amyotrophic lateral sclerosis (ALS), stroke, autoimmune encephalomyelitis, diabetic neuropathy, glaucomatous neuropathy, Alzheimer's disease, and Huntington's disease (HD).
12. The method of claim 11 , wherein the neurological disease or condition is Huntington's disease (HD).
13. The method of claim 12 , wherein the subject is diagnosed with early HD and administering the hIDPSCs to the subject supports a neuroprotective mechanism in the subject.
14. The method of claim 11 , wherein the neurological disease or condition is Parkinson's disease (PD).
15. The method of claim 14 , wherein the subject is diagnosed with PD and administering the hIDPSCs to the subject repairs lost dopaminergic neurons in the subject.
16. The method of claim 7 , wherein the neurological disease or condition is selected from the group consisting of autism, schizophrenia, stroke, ischemia, a motor disorder, and a convulsive disorder.
17. The method of claim 7 , wherein the hIDPSCs express dopamine receptor D2.
18. The method of claim 7 , wherein the neurological disease or condition is treated by the hIDPSCs crossing the BBB.