Single Cell RNA-Sequencing of Cardiac Progenitor Cells Across Patient Age Populations

Human c-kit+ cardiac progenitor cells (CPCs) have seen success in the treatment of heart failure and myocardial dysfunction. However, research has demonstrated the reparative capacity of CPCs appears to be linked to the age of the patient, with younger patients having increased heart function and reduced fibrosis following treatment. We hypothesized that these differences may be driven by differing subtypes of CPCs existing in each donor sample. Using the high-resolution capabilities of single cell RNA-sequencing technologies, we hope to elucidate the different subtypes that may be giving rise to the differences in therapeutic outcomes observed during in vivo studies. In the first study we analyzed the differences between adult CPCs (aCPCs) and neonatal CPCs (nCPCs). In vivo studies indicated injected aCPC had reduced cell retention and cell proliferation due to increased phagocytosis in comparison to nCPCs. We found three distinct subtypes of CPCs following analysis of the data. The two nCPC-enriched clusters correlated strongly with wound healing and cell proliferation, while the third aCPC-enriched cluster indicated some immune response activity. Analysis of selected gene expression in the third cluster indicated reduced expression of CD47, an important anti-phagocytic protein, along with reduced expression of several important growth factor and ECM proteins.6 In the second study we analyzed the differences between pediatric patient populations. Previously published in vivo and in vitro results indicate reduced fibrosis and immune response and increased chemotaxis when using nCPCs in comparison to child CPCs (cCPCs). Subcluster analysis finds cCPC-enriched clusters upregulated in several fibrosis- and immune response-related genes. Clustering of genes indicates genes correlated in chemotaxis to be upregulated in nCPC clusters. We identified the surface proteins versican and ITGA2 to be upregulated in fibrosis-related cluster 6 cells. Flow cytometric analysis using antibodies specific to these proteins identified a cell population with high levels of both proteins, consistent with the gene expression profile identified by the cluster 6 cells. We hope that this research will allow for researchers in the future to better optimize for and predict clinical outcomes prior to injection in autologous CPC-based therapies.M.S

Central excitability contributes to supramaximal volitional contractions in human incomplete spinal cord injury

Individuals with a motor incomplete spinal cord injury (SCI) present clinically with partial control of muscles below the site of the injury, but experience profound weakness which can limit the ability to perform functional tasks such as walking. Interestingly, when individuals with an incomplete SCI are asked to maximally and repeatedly contract their quadriceps muscles, they demonstrate an increase in the peak force generated; individuals without SCI experience a decline in force, or ‘fatigue’. Following these repeated maximal efforts, reflex responses to electrical stimulation over the quadriceps muscle elicited amplified and prolonged, involuntary motor activity. Such responses were not observed prior to the maximal contractions, and were not observed in neurologically intact subjects. This finding suggests that increases in spinal excitability following these maximal efforts may enhance force generating capacity, and provides insight into possible novel therapeutic interventions to restore function following SCI

Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, recovery from SCI typically involves long term rehabilitation. While recovery of walking ability is a primary goal in many patients early after injury, those with a motor incomplete SCI, indicating partial preservation of volitional control, may have the sufficient residual descending pathways necessary to attain this goal. However, despite physical interventions, motor impairments including weakness, and the manifestation of abnormal involuntary reflex activity, called spasticity or spasms, are thought to contribute to reduced walking recovery. Doctrinaire thought suggests that remediation of this abnormal motor reflexes associated with SCI will produce functional benefits to the patient. For example, physicians and therapists will provide specific pharmacological or physical interventions directed towards reducing spasticity or spasms, although there continues to be little empirical data suggesting that these strategies improve walking ability

Using a microprocessor knee (C-Leg) with appropriate foot transitioned individuals with dysvascular transfemoral amputations to higher performance levels: a longitudinal randomized clinical trial

Article evaluating whether advanced prostheses can provide better safety and performance capabilities to maintain and improve quality of life in individuals who are predominantly designated MFCL level K2. This study used a 13 month longitudinal clinical trial to determine the benefits of using a C-Leg and 1M10 foot in individuals at K2 level with transfemoral amputation due to vascular disease

Immediate Adaptations to Post-Stroke Walking Performance Using a Wearable Robotic Exoskeleton

Objective To examine the immediate effects of a hip-assistive wearable robotic exoskeleton on clinical walking performance, walking energetics, gait kinematics, and corticomotor excitability in individuals with stroke. Design Randomized cross-over trial. Setting Research laboratory of a rehabilitation hospital. Participants Twelve individuals (4F/8M, mean age 57.8±7.2) with chronic hemiparetic stroke. Interventions Honda’s Stride Management Assist (SMA) exoskeleton, which provides torque-based flexion and extension assistance at the hip joints during walking. Main Outcome Measures The primary outcome measure was change in self-selected walking speed with the device off vs. with the device on. Secondary outcome measures included changes in clinical endurance, energy expenditure, kinematics, and corticomotor excitability of lower limb muscles. Results In a single session using the device, participants exhibited adaptations over most outcome measures. Self-selected walking speed and peak treadmill speed increased, while oxygen consumption rate decreased during overground and treadmill endurance tests. More symmetric walking patterns were observed during treadmill walking. Changes in corticomotor excitability were highly variable among participants, with a non-significant increase in excitability for the paretic rectus femoris. Conclusions The SMA hip exoskeleton causes immediate positive adaptations in walking performance in individuals with stroke when the device is in use

A smartphone-based online system for fall detection with alert notifications and contextual information of real-life falls

This article presents the results of a prospective study investigating a proof-of-concept, smartphone-based, online system for fall detection and notification. Apart from functioning as a practical fall monitoring instrument, this system may serve as a valuable research tool, enable future studies to scale their ability to capture fall-related data, and help researchers and clinicians to investigate real-falls

Budget impact analysis of robotic exoskeleton use for locomotor training following spinal cord injury in four SCI Model Systems

Background We know little about the budget impact of integrating robotic exoskeleton over-ground training into therapy services for locomotor training. The purpose of this study was to estimate the budget impact of adding robotic exoskeleton over-ground training to existing locomotor training strategies in the rehabilitation of people with spinal cord injury. Methods A Budget Impact Analysis (BIA) was conducted using data provided by four Spinal Cord Injury (SCI) Model Systems rehabilitation hospitals. Hospitals provided estimates of therapy utilization and costs about people with spinal cord injury who participated in locomotor training in the calendar year 2017. Interventions were standard of care walking training including body-weight supported treadmill training, overground training, stationary robotic systems (i.e., treadmill-based robotic gait orthoses), and overground robotic exoskeleton training. The main outcome measures included device costs, training costs for personnel to use the device, human capital costs of locomotor training, device demand, and the number of training sessions per person with SCI. Results Robotic exoskeletons for over-ground training decreased hospital costs associated with delivering locomotor training in the base case analysis. This analysis assumed no difference in intervention effectiveness across locomotor training strategies. Providing robotic exoskeleton overground training for 10% of locomotor training sessions over the course of the year (range 226–397 sessions) results in decreased annual locomotor training costs (i.e., net savings) between $1114 to$4784 per annum. The base case shows small savings that are sensitive to parameters of the BIA model which were tested in one-way sensitivity analyses, scenarios analyses, and probability sensitivity analyses. The base case scenario was more sensitive to clinical utilization parameters (e.g., how often devices sit idle and the substitution of high cost training) than device-specific parameters (e.g., robotic exoskeleton device cost or device life). Probabilistic sensitivity analysis simultaneously considered human capital cost, device cost, and locomotor device substitution. With probabilistic sensitivity analysis, the introduction of a robotic exoskeleton only remained cost saving for one facility. Conclusions Providing robotic exoskeleton for over-ground training was associated with lower costs for the locomotor training of people with SCI in the base case analyses. The analysis was sensitive to parameter assumptions