DIAGNOSTIC AND DRUG SCREENING FOR MOLECULAR SIGNATURES OF EARLY ONSET SPORADIC PARKINSON'S DISEASE

    公开(公告)号:US20210033628A1

    公开(公告)日:2021-02-04

    申请号:US17043272

    申请日:2019-04-05

    摘要: Induced Pluripotent Stem Cell (Ipsc) technology enables the generation and study of living brain tissue relevant to Parkinson's disease (PD) ex vivo. Utilizing cell lines from PD patients presents a powerful discovery system that links cellular phenotypes observed in vitro with real clinical data. Differentiating patient-derived iPSCs towards a dopaminergic (DA) neural fate revealed that these cells exhibit molecular and functional properties of DA neurons in vitro that are observed to significantly degenerate in the substantia nigra of PD patients. Clinical symptoms that drive the generation of other relevant cell types may also yield novel PD-specific phenotypes in vitro that have the potential to lead to new therapeutic avenues for patients with PD. Due to their early onset and non-familial origin, differentiated nervous tissue from these patients offer a key opportunity to discover neuron subtype-specific pathological mechanisms and importantly interrogate the contribution of their genetic background in susceptibility to PD.

    METHODS AND COMPOSITIONS FOR CRYOPRESERVATION OF ENDOTHELIAL CELLS

    公开(公告)号:US20180168144A1

    公开(公告)日:2018-06-21

    申请号:US15838223

    申请日:2017-12-11

    IPC分类号: A01N1/02 C12N5/0797

    摘要: Brain microvascular endothelial cells (BMECS) can be generated from pluripotent stem cells, and possess membrane barrier functions along with capability for maturation into other developing tissues. This cell type has not been successfully frozen with loss of significant viability and/or BMEC functional properties. For example, BMECs can be used to model barrier function in blood brain barrier, by calculating the trans-endothelial resistance (TEER). However, thawed primary BMECs lose TEER resistance. By optimizing cell preparation, freezing media selection, and the controlled freezing, the Inventors have achieved complete recovery of frozen cells, achieving proper tight junction protein expression and physiologically relevant TEER. The freezing methods and compositions described herein, thereby allow for BMECs to be manufactured, frozen and distributed at scale.

    NOVEL DIFFERENTIATION TECHNIQUE TO GENERATE DOPAMINERGIC NEURONS FROM INDUCED PLURIPOTENT STEM CELLS

    公开(公告)号:US20210024886A1

    公开(公告)日:2021-01-28

    申请号:US17041788

    申请日:2019-04-05

    IPC分类号: C12N5/0793

    摘要: Induced Pluripotent Stem Cell (Ipsc) technology enables the generation and study of living brain tissue relevant to Parkinson's disease (PD) ex vivo. Utilizing cell lines from PD patients presents a powerful discovery system that links cellular phenotypes observed in vitro with real clinical data. Differentiating patient-derived iPSCs towards a dopaminergic (DA) neural fate revealed that these cells exhibit molecular and functional properties of DA neurons in vitro that are observed to significantly degenerate in the substantia nigra of PD patients. Clinical symptoms that drive the generation of other relevant cell types may also yield novel PD-specific phenotypes in vitro that have the potential to lead to new therapeutic avenues for patients with PD. Due to their early onset and non-familial origin, differentiated nervous tissue from these patients offer a key opportunity to discover neuron subtype-specific pathological mechanisms and importantly interrogate the contribution of their genetic background in susceptibility to PD.