Building neurovascular tissue from autologous blood for modeling brain-activity DOI Creative Commons
Rhythm Arora, A Bhardwaj, Naresh K. Panda

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract There are no faithful individualized stem cell-based bioengineered neuro-vascularized models that can recapitulate the physiological hemodynamic phenomenon of neuro-vascular coupling (NVC)-the principal behind BOLD (blood oxygen level-dependent) signal in functional neuroimaging, thereby dissuading research exploring brain activity-based investigative studies neurological/neurosensory diseases. This encouraged us to establish a preclinical optoacoustic (Hb/dHb hemoglobin/deoxyhemoglobin) imaging-competent vitro model by employing novel cellular reprograming PITTRep (Plasma Induced Transcriptomics/ epi-Transcriptomics Reprograming) approach. The current approach is based on coaxing autologous blood components ecto-mesodermal lineage intermediates subsequently self-pattern into neurovascular tissue harnessing hemorheological properties RBCs. nature flow non-Newtonian and function RBC concentration /haematocrit when they through regions low shear rates as seen cerebral microcirculation. modification our previous employed Newtonian plasma fluid. blood-derived free from exogenous genetic modification, external growth factors, induced pluripotent cell (iPSC) derivation. uniquely integrates vasculature neurogenesis. reprogramming resulted (in part) serendipitously while testing potential (yet completely unexplored) hypothesis haemodynamic leveraging fluid mechanic feature erythrocytes thrombus formation during ischemic stroke, characterized physiologically intriguing yet clinically meaningful neurological recovery (neuroplasticity) an early time window. study attempted induce “a post stroke-like model” adult neurogenesis with synaptogenesis instructing incorporation varying concentrations. We tried instruct neuroplasticity (a relatively non-resilient under conditions) co-induction niche (NVN). These NVNs marked dendrites, synapses, astrogliosis, microglia activation, factor signaling, thus phenocopying molecular aspects post-stroke induction niches (NVC) was confocal microscopy, scanning electron proteomic profiling, Hb/dHb spectra imaging. checked rotational thromboelastometry (ROTEM), switching adult-to-embryonic hemoglobin confirmed routine typing. also patient-specific sensorineural hearing loss (SNHL) patients. neovascularised tissues intended be for investigating deregulated synaptic plasticity/ long term potentiation underlying poor auditory comprehension outcomes school going kids suffering SNHL greatly compromises their academic performance socio-behavioural-cognitive development. attendant multiomics may have implications developing stem-cell therapies neurosensory cerebrovascular

Language: Английский

Building neurovascular tissue from autologous blood for modeling brain-activity DOI Creative Commons
Rhythm Arora, A Bhardwaj, Naresh K. Panda

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract There are no faithful individualized stem cell-based bioengineered neuro-vascularized models that can recapitulate the physiological hemodynamic phenomenon of neuro-vascular coupling (NVC)-the principal behind BOLD (blood oxygen level-dependent) signal in functional neuroimaging, thereby dissuading research exploring brain activity-based investigative studies neurological/neurosensory diseases. This encouraged us to establish a preclinical optoacoustic (Hb/dHb hemoglobin/deoxyhemoglobin) imaging-competent vitro model by employing novel cellular reprograming PITTRep (Plasma Induced Transcriptomics/ epi-Transcriptomics Reprograming) approach. The current approach is based on coaxing autologous blood components ecto-mesodermal lineage intermediates subsequently self-pattern into neurovascular tissue harnessing hemorheological properties RBCs. nature flow non-Newtonian and function RBC concentration /haematocrit when they through regions low shear rates as seen cerebral microcirculation. modification our previous employed Newtonian plasma fluid. blood-derived free from exogenous genetic modification, external growth factors, induced pluripotent cell (iPSC) derivation. uniquely integrates vasculature neurogenesis. reprogramming resulted (in part) serendipitously while testing potential (yet completely unexplored) hypothesis haemodynamic leveraging fluid mechanic feature erythrocytes thrombus formation during ischemic stroke, characterized physiologically intriguing yet clinically meaningful neurological recovery (neuroplasticity) an early time window. study attempted induce “a post stroke-like model” adult neurogenesis with synaptogenesis instructing incorporation varying concentrations. We tried instruct neuroplasticity (a relatively non-resilient under conditions) co-induction niche (NVN). These NVNs marked dendrites, synapses, astrogliosis, microglia activation, factor signaling, thus phenocopying molecular aspects post-stroke induction niches (NVC) was confocal microscopy, scanning electron proteomic profiling, Hb/dHb spectra imaging. checked rotational thromboelastometry (ROTEM), switching adult-to-embryonic hemoglobin confirmed routine typing. also patient-specific sensorineural hearing loss (SNHL) patients. neovascularised tissues intended be for investigating deregulated synaptic plasticity/ long term potentiation underlying poor auditory comprehension outcomes school going kids suffering SNHL greatly compromises their academic performance socio-behavioural-cognitive development. attendant multiomics may have implications developing stem-cell therapies neurosensory cerebrovascular

Language: Английский

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