Pathological Cell Stretcher
With High Validity to Predict in Vivo Behavior
1) The Mechanics Module reproduces the biomechanics of a TBI, SCI, or concussion pulling the stretchable microelectrode array (MEA) over an indenter to deform, i.e., injure, the cells. Multiple injuries can be produced for investigating the effects of repeated concussions and the link to neurodegerative diseases.
2) The Electrophysiology Module enables electrophysiological measurements before and after stretching (the injury) using the microelectrodes on the stretchable microelectrode array (MEA). Notably, the electrodes stretch with the cells during the injury, i.e., post-injury electrophysiology (cell health) can be readily normalized to pre-injury level.
3) The Imaging Module enables visualization of cells and cellular processes during the injury using optical and fluorescence imaging, e.g., to verify cell adhesion to the substrate or measure the flow of Ca ions.
Our team of experts...
Founder
Phone: +1 (609) 532-9744
Email: oliver@bmseed.com
What is a Physiological Cell Stretcher Used For?
BMSEED’s MEASSuREis an integrated in vitro model for TBI, SCI, and other stretch/compression-induced injuries using stretchable multielectrode array technology.
Every year more than 1.7 million Americans sustain a traumatic brain injury (TBI) or concussion, 220,000 are hospitalized, and 66,000 die. In addition, 12,000-20,000 Americans sustain a spinal cord injury (SCI) annually. Despite the billions of dollars spent on research and drug development over the past decades, little is known about the mechanisms of neurotraumatic injuries, and ALL 30 clinical trials for neuroprotective drugs have failed. Additionally, epidemiological data suggest that a history of traumatic brain injury (TBI) is a significant environmental risk factor in developing Alzheimer’s Disease (AD). Evidence of a link between AD and TBI is that amyloid beta (Abeta) plaques similar to those observed in the early stages of AD have been found in 30% of patients who die acutely after a TBI. Furthermore, repetitive concussions, or mild TBI (mTBI), may lead to permanent degenerative changes including AD, chronic traumatic encephalopathy, and dementia.
In most cases, the primary biomechanical mechanism of the cell damage in a TBI, concussion, and SCI is a pathological stretch of the brain tissue during the impact. In vitro TBI models for early screening of novel therapeutics need the capability to assess the subtle but important changes in health and function of the injured neurons. Electrophysiology is a great method to assess changes in cellular health and function because the technique directly measures what is most critical to the function of neurons: the generation and transmission of electrical signals.
MEASSuRE enables functional drug screening, reproduction of the biomechanics of the injury, and measuring cell health and function before and after the injury with stretchable microelectrodes.
Applications for Pathological Cell Stretchers
1. Pathological Cell Stretchers for Neurotrauma
BMSEED’s pathological cell stretcher, or MEASSuRE, can provide insights into neurotrauma by modeling the biomechanical forces that cause neuronal injury and comparing post-injury electrophysiology to their pre-injury levels. MEASSuRE can replicate the mechanical stresses involved in neurotraumas such as traumatic brain injury (TBI) and spinal cord injury (SCI), and assess how these stresses affect neuronal health and function. The effectiveness of neuroprotective treatments to minimize the damage after injury can therefore be readily assessed.
2. Pathological Cell Stretchers for Concussion
BMSEED’s pathological cell stretcher, or MEASSuRE, allows researchers and physicians to develop improved concussion protocols that are based on the electrophysiology of the underlying injury rather than cognitive assessments. Researchers can develop more accurate and physiologically relevant concussion protocols by analyzing the changes in neuronal electrical activity following a concussion-like injury simulated by MEASSuRE. This can lead to improved strategies for diagnosis, treatment, and management of concussions as researchers learn about the injury mechanisms.
3. Pathological Cell Stretchers for Muscle Injury & Pain
BMSEED’s pathological cell stretcher, or MEASSuRE, allows researchers to investigate the mechanism of muscle injuries that are caused by excessive tension or compression, and the evaluation of drugs to speed up recovery. MEASSuRE can simulate these mechanical stresses and evaluate their effects on muscle cell health and function. Researchers can then test various treatments and drugs aimed at reducing muscle damage and accelerating recovery to develop therapies for muscle injury and chronic pain conditions.
4. Pathological Cell Stretchers for Stem Cell Repair Mechanism
Stem cells are involved in repair processes after injury in different parts of the body, e.g., in the brain after a traumatic brain injury. The mechanism of the activation of the mechanoreceptors is not understood. BMSEED’s pathological cell stretcher, or MEASSuRE, can be used to study how mechanoreceptors on stem cells are activated in response to mechanical stress, and how this contributes to the repair processes after injury. By simulating injury conditions and monitoring stem cell behavior, researchers can gain insights into the mechanisms that drive stem cell activation, differentiation, and repair to develop more effective regenerative therapies.
5. Pathological Cell Stretchers for Alzheimer’s Disease
Neurodegenerative diseases such as Alzheimer’s disease (AD) have common pathological pathways with TBI, e.g., the build-up of amyloid-plaques. BMSEED’s pathological cell stretcher, or MEASSuRE, can contribute to AD research by replicating the pathological conditions similar to those observed in TBI, such as amyloid plaque formation. By using MEASSuRE to assess how these conditions affect neuronal function and health, researchers can evaluate the efficacy of new drug candidates in mitigating the effects of amyloid plaques and other AD-related changes in neuronal activity.
Example for the Use of Pathological Cell Stretchers:
Assessing Long Term Potentiation in Organotypic Hippocampal Slice Cultures (OHSCs) after TBI
OHSC-based in vitro models maintain the structure of the hippocampus and provide a platform to study the interactions of multiple cell types. Long term potentiation (LTP) is a cellular in vitro correlate of learning and memory which is based on synaptic plasticity. Long term potentiation is decreased after repeated mild injury. This study demonstrates how the use of stretchable microelectrode arrays (sMEAs) in the MEASSuRE platform is critical in detecting the impairment of LTP, i.e., the reduction in synaptic plasticity, after a TBI.
After injury, induction of LTP through high frequency stimulation does not increase magnitude of response that is seen in sham injured OHSCs
Methods
OHSCs derived from hippocampi of P8-10 Sprague-Dawley rats were placed on the sMEAs and kept in an incubator for at least 10 days. Spontaneous activity and stimulus response (SR) curves were recorded with the Electrophysiology Module of MEASSuRE. The slices (one per sMEA) were then subjected to moderate biaxial stretch injury (average strain: 16.2%, strain rate: 16.8 s-1) with the Mechanics Module of MEASSuRE, or sham injury as control. The actual tissue strains were confirmed with high-speed video recorded with the Imaging Module of MEASSuRE. 24 hours after injury, a second recording of spontaneous activity and SR curves. To measure plasticity, long term potentiation was induced with 3 rounds of 100 pulses at 100Hz separated by 10 seconds applied once at i50. LTP percentage values were calculated as the magnitude of the responses measured 50-60 minutes after plasticity induction, normalized to the last 10 minutes of baseline.
Results
There was no change in the overall firing rate, the magnitude of the spontaneous activity, SR parameters, or the average number of bursts before and after injury. However, there was a decrease in the spike length of the average burst after injury (7.78 ± 0.71 vs 5.94 ± 0.16, N = 10-12 slices, *p<0.05). LTP deficits 24 hours after injury were robust (48.06 ± 13.50 vs -3.62 ± 2.79%, N=4 slices **p<0.01, see Figure) compared to baseline.
Conclusions
Stretchable microelectrode arrays (sMEAs) provide a unique way to study electrical activity in the same OHSCs before and after injury. In this example, a large LTP deficits after injury was detected, which can be used as a model to assess therapeutics for TBI in vitro.
Our team of experts...
Founder
Phone: +1 (609) 532-9744
Email: oliver@bmseed.com
Frequently Asked Questions About our Pathological Cell Stretcher
1. What types of injuries can be modeled using the pathological cell stretcher?
BMSEED’s pathological cell stretcher, or MEASSuRE, is designed to reproduce the mechanical forces involved in injury by stretching and deforming cells or tissues on our stretchable microelectrode arrays (sMEAs). These injuries can include traumatic brain injury (TBI), spinal cord injury (SCI), concussions and repeated concussions, and more. This allows researchers to study how different types of mechanical deformation that cells experience during these types of injuries affect their health and function.
2. How does the Mechanics Module work to simulate injuries?
To simulate these injuries, the Mechanics Module of the pathological cell stretcher pulls the stretchable microelectrode array (sMEA) over an indenter, applying precise mechanical stresses to the sMEA and cells or tissue in the well. This stretch replicates the biomechanical forces in vitro that the cells would experience during a TBI, SCI, or concussion in vivo. The Mechanics Module can be additionally customized to simulate single or repeated injuries, providing insights into cellular responses to mechanical deformation over time (e.g. repeated concussions, etc.). The Mechanics Module can be used independently or concurrently with the Electrophysiology and/or Imaging Modules (each Module can be purchased as a stand-alone unit).
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The Electrophysiology Module of the pathological cell stretcher is required to assess how mechanical injuries affect cell health and function using the electrodes embedded in the sMEA surface that contact the cells. By recording electrical activity from cells before and after the stretch injury, researchers can quantify changes in neuronal firing rates, synaptic responses, and other electrophysiological parameters. This offers direct insight into how injury influences cell health and function, and how potential treatments can be integrated to minimize these effects. The pathological cell stretcher can be used with or without the Electrophysiology Module, depending on the researcher’s needs.
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The purpose of the Imaging Module in the pathological cell stretcher is to provide real-time visualization of cellular responses before, during, and after mechanical injury. Currently, the Imaging Module utilizes optical imaging techniques to observe cell adhesion, morphology changes, and other imaging parameters. Fluorescence imaging techniques for observing intracellular processes, such as calcium ion flow, can be integrated with the pathological cell stretcher upon request. This visual data can complement the Electrophysiology Module’s measurements for a more comprehensive view of how mechanical stress affects cells at both the structural and functional levels.
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BMSEED’s pathological cell stretcher, or MEASSuRE, offers several advantages over traditional in vivo models. MEASSuRE provides a more controlled environment in which mechanical forces can be precisely applied to cells with electrophysiological and optical measurements. The direct measurement of cellular responses without the complexity and variability associated with animal models allows for more consistent and reproducible injury conditions.