Ventral Midbrain Dopaminergic Progenitor Cell Enrichment via CD117 Marker
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Solution Overview
Problem
Current methods for generating ventral midbrain dopaminergic progenitor cells from pluripotent and/or multipotent stem cells result in a mixture of ventral midbrain and ventral hindbrain dopaminergic progenitor cells, making it difficult to determine the best performing cell phenotype for treating Parkinson's disease, as both types show similar expression profiles and the differentiation protocols do not effectively separate these cells.
Innovation Solution
The use of CD117 as a specific marker for ventral midbrain dopaminergic progenitor cells and CD171 for ventral hindbrain dopaminergic progenitor cells allows for the separation and enrichment of ventral midbrain dopaminergic progenitor cells, enabling the generation of a substantially pure composition of these cells, which can be achieved in a closed system under GMP conditions and through automated processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If current differentiation protocols are used to generate ventral dopaminergic progenitor cells from pluripotent and/or multipotent stem cells, then a mixture of ventral midbrain and ventral hindbrain dopaminergic progenitor cells is obtained, but it is difficult to determine the best performing cell phenotype for treating Parkinson's disease
Solution Approach 1:
The patent uses differential expression of surface markers (CD117 and CD171) as molecular 'colors' to distinguish between ventral midbrain and ventral hindbrain dopaminergic progenitor cells. By detecting which markers are present or absent, the protocol can identify and separate the desired cell phenotype, resolving the difficulty of determining the best performing cell type for Parkinson's disease treatment.
2Productivity
If standard differentiation protocols are applied, then dopaminergic progenitor cells are generated, but ventral midbrain and ventral hindbrain dopaminergic progenitor cells show high similarity in expression profiles making separation difficult
Solution Approach 1:
The patent applies the principle of local quality by identifying specific surface marker expression patterns (CD117 positive/CD171 negative for ventral midbrain; CD117 negative/CD171 positive for ventral hindbrain) that locally distinguish between the two cell subtypes. This allows the differentiation protocol to maintain overall productivity while achieving precise cell subtype discrimination through marker-specific identification.
3Ease of operation
If a mixture of cell types is used for cell replacement therapy, then treatment can be administered, but the effectiveness is reduced due to inclusion of unwanted ventral hindbrain dopaminergic progenitor cells
Solution Approach 1:
The patent applies the extraction principle by using surface marker detection to identify and separate the desired ventral midbrain dopaminergic progenitor cells (CD117 positive, CD171 negative) from the unwanted ventral hindbrain dopaminergic progenitor cells in the mixture. This extraction of the target cell population from the heterogeneous mixture improves treatment reliability while maintaining ease of administration through enriched, purified cell populations.
Data Source
AI summary
The present invention discloses an in vitro method for the generation of a cell composition comprising or consisting of ventral midbrain dopaminergic progenitor cells from a cell composition comprising pluripotent and/or multipotent stem cells, the method comprising the steps of A) differentiating said pluripotent and/or multipotent stem cells into ventral dopaminergic progenitor cells, thereby generating a cell composition comprising ventral dopaminergic progenitor cells comprising ventral midbrain dopaminergic progenitor cells and ventral hindbrain dopaminergic progenitor cells, and B) Enriching CD117 positive cells from said cell composition comprising ventral dopaminergic progenitor cells by using an antigen binding molecule specific for the CD117 antigen, thereby generating said cell composition comprising or consisting of ventral midbrain dopaminergic progenitor cells. Cell compositions obtainable by said method are also disclosed.