Derivation and differentiation of human induced pluripotent stem cells (hiPSCs) provide the opportunity to generate medically important cell types from individual patients and patient populations for research and the development of potential cell therapies. This technology allows disease modeling and drug screening to be carried out using diverse population cohorts and with more relevant cell phenotypes than can be accommodated using traditional immortalized cell lines. However, technical complexities in the culture and differentiation of hiPSCs, including lack of scale and standardization and prolonged experimental timelines, limit the adoption of this technology for many large-scale studies, including personalized drug screening. The entry of reproducible end-to-end automated workflows for hiPSC culture and differentiation, demonstrated on commercially available platforms, provides enhanced accessibility of this technology for both research laboratories and commercial pharmaceutical testing. Here we have utilized TECAN Fluent automated cell culture workstations to perform hiPSC culture and differentiation in a reproducible and scalable process to generate patient-derived retinal pigment epithelial cells for downstream use, including drug testing. hiPSCs derived from multiple donors with age-related macular degeneration (AMD) were introduced into our automated workflow, and cell lines were cultured and differentiated into retinal pigment epithelium (RPE). Donor hiPSC-RPE lines were subsequently entered in an automated drug testing workflow to measure mitochondrial function after exposure to “mitoactive” compounds. This work demonstrates scalable, reproducible culture and differentiation of hiPSC lines from individuals on the TECAN Fluent platform and illustrates the potential for end-to-end automation of hiPSC-based personalized drug testing.
Purpose: Freezing of gait (FOG) is a disabling phenomenon defined by the periodic absence or reduction of forward progression of the feet despite the intention to walk. We sought to understand whether Google Glass (GG), a lightweight wearable device that provides simultaneous visual-auditory cues, might improve FOG in parkinsonism. Methods: Patients with parkinsonism and FOG utilized GG custom-made auditory-visual cue applications: "Walk With Me" and "Unfreeze Me" in a single session intervention. We recorded ambulation time with and without GG under multiple conditions including 25 feet straight walk, dual task of performing serial 7's while straight walking, 180 degree turn after walking 25 feet, and walking through a doorway. FOG and patient experience questionnaires were administered. Results: Using the GG "Walk With Me" program, improvements were noted in the following: average 25 feet straight walk by 0.32 s (SD 2.12); average dual task of serial 7's and 25 feet straight walk by 1.79 s (SD 2.91); and average walk through doorway by 0.59 s (SD 0.81). Average 180 degree turn after 25 feet walk worsened by 1.89 s (SD 10.66). Using the "Unfreeze Me" program, only the average dual task of serial 7's and 25 feet straight walk improved (better by 0.82 s (SD 3.08 sec). All other tasks had worse performance in terms of speed of completion. Conclusion: This feasibility study provides preliminary data suggesting that some walking tasks may improve with GG, which uses various musical dance programs to provide visual and auditory cueing for patients with FOG. ä IMPLICATIONS FOR REHABILITATION Freezing of gait in parkinsonian syndromes is a disabling motor block described by patients as having their feet stuck to the floor leading to difficulty in initiation of gait and increased risk for falls. Wearable assistive devices such as Google Glass TM use visual and auditory cueing that may improve gait pattern in patients with freezing of gait. Augmented reality programs using wearable assistive devices are a home-based therapy, with the potential for reinforcing physical therapy techniques; this is especially meaningful during the COVID-19 pandemic when access to both medical and rehabilitative care has been curtailed.
Background: Parkinson's disease (PD) is the second leading neurodegenerative disease worldwide. Important advances in monitoring and treatment have been made in recent years. This article reviews literature on utility of smartphone applications in monitoring PD symptoms that may ultimately facilitate improved patient care, and on movement modulation as a potential therapeutic.Review Summary: Novel mobile phone applications can provide onetime and/or continuous data to monitor PD motor symptoms in person or remotely, that may support precise therapeutic adjustments and management decisions. Apps have also been developed for medication management and treatment.Conclusions: Smartphone applications provide a wide array of platforms allowing for meaningful short-term and long-term data collection and are also being tested for intervention. However, the variability of the applications and the need to translate complicated sensor data may hinder immediate clinical applicability. Future studies should involve stake-holders early in the design process to promote usability and streamline the interface between patients, clinicians, and PD apps.
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