Compositions comprising stem cells expressing mesenchymal and neuronal markers and uses thereof to treat neurological disease
Inventors
Kerkis, Irina • Kerkis, Alexandre
Assignees
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Publication Number
US-11207352-B2
Publication Date
2021-12-28
Expiration Date
Abstract
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.
Core Innovation
The invention relates to a cryopreserved pharmaceutical composition comprising undifferentiated human immature dental pulp stem cells (hIDPSCs). The composition requires that at least 80% of the hIDPSCs express DARPP32 and BDNF, and that at least 90% of the hIDPSCs express CD44 and CD13. The undifferentiated hIDPSCs maintain the capacity to form multiple cell types including neuronal cells, fibroblast cells, and perivascular cells.
The disclosed approach is positioned as providing neurogenesis and neuroprotection by using CD44 and CD13-positive hIDPSCs with systemic delivery intended to enable blood-brain barrier (BBB) crossing. The problem addressed is treatment of neurodegenerative diseases, including Huntington’s disease (HD), Parkinson’s disease (PD), and Alzheimer’s disease (AD), where other stem-cell approaches have limitations.
The disclosure further characterizes the hIDPSCs and intended in vivo behavior, including localization to brain compartments such as capillaries and the subventricular zone (SVZ), with histological and immunohistochemical evidence of neuronal and mature neuron marker expression. In a 3-nitropropionic acid (3-NP) HD rat model, transplanted cells are reported to show reduced neuron loss and improved survival metrics, and late harvest populations are described as showing higher endogenous BDNF/NTF secretion.
Claims Coverage
The independent claim covers a cryopreserved pharmaceutical composition of undifferentiated hIDPSCs defined by specific marker-expression thresholds (DARPP32/BDNF and CD44/CD13) while retaining multi-lineage differentiation capacity into neuronal, fibroblast, and perivascular cells.
Cryopreserved undifferentiated hIDPSCs with DARPP32/BDNF expression threshold
Undifferentiated hIDPSCs in a cryopreserved pharmaceutical composition wherein at least 80% of the hIDPSCs express DARPP32 and BDNF.
hIDPSCs with CD44 and CD13 expression threshold
Undifferentiated hIDPSCs in a cryopreserved pharmaceutical composition wherein at least 90% of the hIDPSCs express CD44 and CD13.
Multi-lineage capacity of undifferentiated hIDPSCs
Undifferentiated hIDPSCs that maintain the capacity to form multiple cell types including neuronal cells, fibroblast cells, and perivascular cells.
Overall, the claim coverage centers on a cryopreserved pharmaceutical composition of undifferentiated hIDPSCs that meet quantitative marker-expression thresholds for DARPP32/BDNF and CD44/CD13 and retain the ability to form neuronal, fibroblast, and perivascular cell types.
Stated Advantages
Neurogenesis and neuroprotection are described in connection with systemic delivery intended to cross the blood-brain barrier (BBB).
Localization to brain compartments including capillaries and the subventricular zone (SVZ) is described.
In the 3-nitropropionic acid (3-NP) HD rat model, reduced neuron loss and improved survival metrics are described.
Documented Applications
Treatment approaches are described for neurodegenerative diseases including Huntington’s disease (HD) and Parkinson’s disease (PD), with early HD neuroprotection and PD outcomes described as involving dopaminergic neuron repair.
The disclosure describes use of the 3-nitropropionic acid (3-NP) HD rat model to assess engraftment and reported neuroprotective outcomes.
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