Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening.

Patient-derived cellular models become an increasingly powerful tool to model human diseases for precision medicine approaches. The identification of robust cellular disease phenotypes in these models paved the way towards high throughput screenings (HTS) including the implementation of laboratory advanced automation. However, maintenance and expansion of cells for HTS remains largely manual work. Here, we describe an integrated, complex automated platform for HTS in a translational research setting also designed for maintenance and expansion of different cell types. The comprehensive design allows automation of all cultivation steps and is flexible for development of methods for variable cell types. We demonstrate protocols for controlled cell seeding, splitting and expansion of human fibroblasts, induced pluripotent stem cells (iPSC), and neural progenitor cells (NPC) that allow for subsequent differentiation into different cell types and image-based multiparametric screening. Furthermore, we provide automated protocols for neuronal differentiation of NPC in 2D culture and 3D midbrain organoids for HTS. The flexibility of this multitask platform makes it an ideal solution for translational research settings involving experiments on different patient-derived cellular models for precision medicine.

[Somatoform disorder or neurological syndrome? Complex mental and movement disorder and autonomic dysfunction in a 65-year-old patient - Case 1/2011]. / Somatoforme Störung oder neurologisches Syndrom? Komplexe psychische, vegetative und motorische Störungen bei einer 65-jährigen Patientin - Fall 1/2011.

HISTORY AND ADMISSION FINDINGS: A 65-year-old female patient presented with increasing vertigo, tendency to fall, dry cough and, in addition, numerous psychic and somatic symptoms since 6 years. Former diagnostic attempts did not yield clarifying results. In part, the patient had not followed up on former recommendations for further diagnostic procedures. With a suspected somatization disorder the patient was admitted to the Department of Psychosomatic Medicine. INVESTIGATIONS: The neurological examination at admission revealed vertical oculomotor palsy and tendency to fall backwards indicating an affection of the brain stem. A magnetic resonance imaging of the head showed atrophy of the mesencephalon. DIAGNOSIS AND TREATMENT: In light of these findings the patient was diagnosed Steele-Richardson-Olszewksi syndrome. The therapy which comprises training measures and medication with a cholinesterase inhibitor aims to retain neuropsychological and motional abilities. Besides, psychotherapy is offered alongside to help the patient to cope with the disease. CONCLUSIONS: Treating patients with somatic and psychological symptoms calls for careful anamnestic exploration and clinical examination. Psychological alterations following neurological affection of the brain can imitate somatization disorder.

Therapeutic strategies for Parkinson's disease based on data derived from genetic research.

Following the identification of mutations in alpha-synuclein as the cause of some rare forms of familial Parkinson's disease (PD), genetic research has uncovered numerous gene loci of PD. Meanwhile, several neurodegenerative diseases have been shown to accumulate a-synuclein in neuronal and glial cells summarizing this group of diseases as synucleinopathies. All currently known gene defects causing PD alter the ubiquitin-proteasomal pathway of protein degradation. Identification of these disease mutations allows studying the functional consequences which lead to cellular dysfunction and cell death in cell culture and transgenic animal models, to identify therapeutic targets and to test potential protective strategies in these models.