PFAS assessment in fish - Samples from Illinois waters.

Per- and Polyfluoroalkyl substances (PFAS) have been widely used in various industries, including pesticide production, electroplating, packaging, paper making, and the manufacturing of water-resistant clothes. This study investigates the levels of PFAS in fish tissues collected from four target waterways (15 sampling points) in the northwestern part of Illinois during 2021-2022. To assess accumulation, concentrations of 17 PFAS compounds were evaluated in nine fish species to potentially inform on exposure risks to local sport fishing population via fish consumption. At least four PFAS (PFHxA, PFHxS, PFOS, and PFBS) were detected at each sampling site. The highest concentrations of PFAS were consistently found in samples from the Rock River, particularly in areas near urban and industrial activities. PFHxA emerged as the most accumulated PFAS in the year 2022, while PFBS and PFOS dominated in 2021. Channel Catfish exhibited the highest PFAS content across different fish species, indicating its bioaccumulation potential across the food chain. Elevated levels of PFOS were observed in nearly all fish, indicating the need for careful consideration of fish consumption. Additional bioaccumulation data in the future years is needed to shed light on the sources and PFAS accumulation potential in aquatic wildlife in relation to exposures for potential health risk assessment.

Highly-Specific Single-Stranded Oligonucleotides and Functional Nanoprobes for Clinical Determination of Chlamydia Trachomatis and Neisseria Gonorrhoeae Infections.

Early detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is the key to controlling the spread of these bacterial infections. An important step in developing biosensors involves identifying reliable sensing probes against specific genetic targets for CT and NG. Here, the authors have designed single-stranded oligonucleotides (ssDNAs) targeting mutually conserved genetic regions of cryptic plasmid and chromosomal DNA of both CT and NG. The 5'- and 3'- ends of these ssDNAs are differentially functionalized with thiol groups and coupled with gold nanoparticles (AuNP) to develop absorbance-based assay. The AuNPs agglomerate selectively in the presence of its target DNA sequence and demonstrate a change in their surface plasmon resonance. The optimized assay is then used to detect both CT and NG DNA extracted from 60 anonymized clinical samples with a clinical sensitivity of ∼100%. The limit of detection of the assays are found to be 7 and 5 copies/µL for CT and NG respectively. Furthermore, it can successfully detect the DNA levels of these two bacteria without the need for DNA extraction and via a lateral flow-based platform. These assays thus hold the potential to be employed in clinics for rapid and efficient monitoring of sexually transmitted infections.

Sensor technologies for the detection and monitoring of endocrine-disrupting chemicals.

Endocrine-disrupting chemicals (EDCs) are a class of man-made substances with potential to disrupt the standard function of the endocrine system. These EDCs include phthalates, perchlorates, phenols, some heavy metals, furans, dimethoate, aromatic hydrocarbons, some pesticides, and per- and polyfluoroalkyl substances (PFAS). EDCs are widespread in the environment given their frequent use in daily life. Their production, usage, and consumption have increased many-fold in recent years. Their ability to interact and mimic normal endocrine functions makes them a potential threat to human health, aquatics, and wild life. Detection of these toxins has predominantly been done by mass spectroscopy and/or chromatography-based methods and to a lesser extent by advanced sensing approaches such as electrochemical and/or colorimetric methods. Instrument-based analytical techniques are often not amenable for onsite detection due to the lab-based nature of these detecting systems. Alternatively, analytical approaches based on sensor/biosensor techniques are more attractive because they are rapid, portable, equally sensitive, and eco-friendly. Advanced sensing systems have been adopted to detect a range of EDCs in the environment and food production systems. This review will focus on advances and developments in portable sensing techniques for EDCs, encompassing electrochemical, colorimetric, optical, aptamer-based, and microbial sensing approaches. We have also delineated the advantages and limitations of some of these sensing techniques and discussed future developments in sensor technology for the environmental sensing of EDCs.

Longitudinal Assessment of Diagnostic Test Performance Over the Course of Acute SARS-CoV-2 Infection.

BACKGROUND: Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. METHODS: In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. RESULTS: Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. CONCLUSIONS: RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.

Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period. WHAT IS ADDED BY THIS REPORT?: We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.

Superior breast cancer metastasis risk stratification using an epithelial-mesenchymal-amoeboid transition gene signature.

BACKGROUND: Cancer cells are known to display varying degrees of metastatic propensity, but the molecular basis underlying such heterogeneity remains unclear. Our aims in this study were to (i) elucidate prognostic subtypes in primary tumors based on an epithelial-to-mesenchymal-to-amoeboid transition (EMAT) continuum that captures the heterogeneity of metastatic propensity and (ii) to more comprehensively define biologically informed subtypes predictive of breast cancer metastasis and survival in lymph node-negative (LNN) patients. METHODS: We constructed a novel metastasis biology-based gene signature (EMAT) derived exclusively from cancer cells induced to undergo either epithelial-to-mesenchymal transition (EMT) or mesenchymal-to-amoeboid transition (MAT) to gauge their metastatic potential. Genome-wide gene expression data obtained from 913 primary tumors of lymph node-negative breast cancer (LNNBC) patients were analyzed. EMAT gene signature-based prognostic stratification of patients was performed to identify biologically relevant subtypes associated with distinct metastatic propensity. RESULTS: Delineated EMAT subtypes display a biologic range from less stem-like to more stem-like cell states and from less invasive to more invasive modes of cancer progression. Consideration of EMAT subtypes in combination with standard clinical parameters significantly improved survival prediction. EMAT subtypes outperformed prognosis accuracy of receptor or PAM50-based BC intrinsic subtypes even after adjusting for treatment variables in 3 independent, LNNBC cohorts including a treatment-naïve patient cohort. CONCLUSIONS: EMAT classification is a biologically informed method that provides prognostic information beyond that which can be provided by traditional cancer staging or PAM50 molecular subtype status and may improve metastasis risk assessment in early stage, LNNBC patients, who may otherwise be perceived to be at low metastasis risk.

Publisher Correction: Combining Biomarkers with EMR Data to Identify Patients in Different Phases of Sepsis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Environmental adaptive management: Application on submarine mine tailings disposal.

Marine tailings disposal from mineral production is expected to have an environmental impact. In this case study we use a discharge of limestone processing tailings to a Norwegian fjord to describe an adaptive management process. The aim of the paper is to describe the development of an environmental adaptive management system (EAMS), contrasted with management simply based on the quantity of the discharge. The main driver for developing a new management system for the submarine tailings deposits was a desire to establish a system based on what was perceived as important to all stakeholders, that is, environmental impact. Involvement of stakeholders is essential, and a resource group with members from fisheries, local interest organizations, scientists, independent experts, and managers from the mining company jointly defined common sets of acceptance criteria to evaluate impact. Introduction of an EAMS has resulted in a change in the company's view of the impact their activity has on the environment and in an increased willingness to initiate monitoring and research to reduce knowledge gaps and uncertainty and impact on the marine environment. Environmental adaptive management has facilitated the development of a more ecologically relevant, integrated, and focused submarine tailings deposits management. Integr Environ Assess Manag 2019;15:575-583. © 2019 SETAC.

The impact of mechanically stimulated muscle-derived stromal cells on aged skeletal muscle.

Perivascular stromal cells, including mesenchymal stem/stromal cells (MSCs), secrete paracrine factor in response to exercise training that can facilitate improvements in muscle remodeling. This study was designed to test the capacity for muscle-resident MSCs (mMSCs) isolated from young mice to release regenerative proteins in response to mechanical strain in vitro, and subsequently determine the extent to which strain-stimulated mMSCs can enhance skeletal muscle and cognitive performance in a mouse model of uncomplicated aging. Protein arrays confirmed a robust increase in protein release at 24h following an acute bout of mechanical strain in vitro (10%, 1Hz, 5h) compared to non-strain controls. Aged (24month old), C57BL/6 mice were provided bilateral intramuscular injection of saline, non-strain control mMSCs, or mMSCs subjected to a single bout of mechanical strain in vitro (4×104). No significant changes were observed in muscle weight, myofiber size, maximal force, or satellite cell quantity at 1 or 4wks between groups. Peripheral perfusion was significantly increased in muscle at 4wks post-mMSC injection (p<0.05), yet no difference was noted between control and preconditioned mMSCs. Intramuscular injection of preconditioned mMSCs increased the number of new neurons and astrocytes in the dentate gyrus of the hippocampus compared to both control groups (p<0.05), with a trend toward an increase in water maze performance noted (p=0.07). Results from this study demonstrate that acute injection of exogenously stimulated muscle-resident stromal cells do not robustly impact aged muscle structure and function, yet increase the survival of new neurons in the hippocampus.

Combining Biomarkers with EMR Data to Identify Patients in Different Phases of Sepsis.

Sepsis is a leading cause of death and is the most expensive condition to treat in U.S. hospitals. Despite targeted efforts to automate earlier detection of sepsis, current techniques rely exclusively on using either standard clinical data or novel biomarker measurements. In this study, we apply machine learning techniques to assess the predictive power of combining multiple biomarker measurements from a single blood sample with electronic medical record data (EMR) for the identification of patients in the early to peak phase of sepsis in a large community hospital setting. Combining biomarkers and EMR data achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.81, while EMR data alone achieved an AUC of 0.75. Furthermore, a single measurement of six biomarkers (IL-6, nCD64, IL-1ra, PCT, MCP1, and G-CSF) yielded the same predictive power as collecting an additional 16 hours of EMR data(AUC of 0.80), suggesting that the biomarkers may be useful for identifying these patients earlier. Ultimately, supervised learning using a subset of biomarker and EMR data as features may be capable of identifying patients in the early to peak phase of sepsis in a diverse population and may provide a tool for more timely identification and intervention.

3D Printed Stem-Cell-Laden, Microchanneled Hydrogel Patch for the Enhanced Release of Cell-Secreting Factors and Treatment of Myocardial Infarctions.

Over the past several years, biomaterials loaded with mesenchymal stem cells (MSCs) have increasingly been used to reduce the myocardial fate of postinfarction collagen deposition and scar tissue formation. Despite successful gains, therapeutic efficacy has remained limited because of restricted transport of cell-secreting factors at the site of implantation. We hypothesized that an MSC-laden hydrogel patch with multiple microchannels would retain transplanted cells on target tissue and support transport of cell-secreting factors into tissue. By doing so, the gel patch will improve the therapeutic potential of the cells and minimize the degradation of myocardial tissue postinfarction. To examine this hypothesis, a stereolithographic apparatus (SLA) was used to introduce microchannels of controlled diameters (e.g., 500 and 1000 µm) during in situ cross-linking reaction of poly(ethylene glycol)dimethacrylate solution suspended with cells. Placement of the MSC-laden, microchanneled gel patch on the occluded left coronary artery in a murine model showed significant improvement in the ejection fraction, fractional shortening, and stroke volume, compared with gel patches without MSCs and MSC-laden gel patches without microchannels. In particular, the microchannels significantly reduced the number of cells required to recover cardiac function, while minimizing cardiac remodeling. In sum, the microchanneled gel patch would provide a means to prevent abnormal fibrosis resulting from acute ischemic injury.

Impact of ß-hydroxy ß-methylbutyrate (HMB) on age-related functional deficits in mice.

ß-Hydroxy ß-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine. Recent studies demonstrate a decline in plasma HMB concentrations in humans across the lifespan, and HMB supplementation may be able to preserve muscle mass and strength in older adults. However, the impact of HMB supplementation on hippocampal neurogenesis and cognition remains largely unexplored. The purpose of this study was to simultaneously evaluate the impact of HMB on muscle strength, neurogenesis and cognition in young and aged mice. In addition, we evaluated the influence of HMB on muscle-resident mesenchymal stem/stromal cell (Sca-1+CD45-; mMSC) function to address these cells potential to regulate physiological outcomes. Three month-old (n=20) and 24 month-old (n=18) female C57BL/6 mice were provided with either Ca-HMB or Ca-Lactate in a sucrose solution twice per day for 5.5weeks at a dose of 450mg/kg body weight. Significant decreases in relative peak and mean force, balance, and neurogenesis were observed in aged mice compared to young (age main effects, p≤0.05). Short-term HMB supplementation did not alter activity, balance, neurogenesis, or cognitive function in young or aged mice, yet HMB preserved relative peak force in aged mice. mMSC gene expression was significantly reduced with age, but HMB supplementation was able to recover expression of select growth factors known to stimulate muscle repair (HGF, LIF). Overall, our findings demonstrate that while short-term HMB supplementation does not appear to affect neurogenesis or cognitive function in young or aged mice, HMB may maintain muscle strength in aged mice in a manner dependent on mMSC function.

In vivo evaluation of adipose- and muscle-derived stem cells as a treatment for nonhealing diabetic wounds using multimodal microscopy.

Impaired skin wound healing is a significant comorbid condition of diabetes, which often results in nonhealing diabetic ulcers due to poor peripheral microcirculation, among other factors. The effectiveness of the regeneration of adipose-derived stem cells (ADSCs) and muscle-derived stem cells (MDSCs) was assessed using an integrated multimodal microscopy system equipped with two-photon fluorescence and second-harmonic generation imaging. These imaging modalities, integrated in a single platform for spatial and temporal coregistration, allowed us to monitor in vivo changes in the collagen network and cell dynamics in a skin wound. Fluorescently labeled ADSCs and MDSCs were applied topically to the wound bed of wild-type and diabetic (db/db) mice following punch biopsy. Longitudinal imaging demonstrated that ADSCs and MDSCs provided remarkable capacity for improved diabetic wound healing, and integrated microscopy revealed a more organized collagen remodeling in the wound bed of treated mice. The results from this study verify the regenerative capacity of stem cells toward healing and, with multimodal microscopy, provide insight regarding their impact on the skin microenvironment. The optical method outlined in this study, which has the potential for in vivo human use, may optimize the care and treatment of diabetic nonhealing wounds.

Diet-induced obesity regulates adipose-resident stromal cell quantity and extracellular matrix gene expression.

Adipose tissue expansion during periods of excess nutrient intake requires significant turnover of the extracellular matrix (ECM) to allow for maximal lipid filling. Recent data suggest that stromal cells may be a primary contributor to ECM modifications in visceral adipose. The purpose of this study was to investigate the capacity for high fat diet (HFD)-induced obesity to alter adipose-derived stromal cell (ADSC) relative quantity and ECM gene expression, and determine the extent to which exercise training can mitigate such changes. Male C57BL/6J mice were placed on control or HFD for 8weeks prior to and following initiation of a 16week treadmill exercise program. ADSCs (Sca-1(+)CD45(-)) were isolated from epididymal adipose tissue and mRNA was evaluated using high throughput qPCR. Stromal cells were also obtained from skeletal muscle (MDSC). HFD decreased the quantity of ADSCs and markedly altered gene expression related to ECM remodeling (Col1α1, MMP2, MMP9, Timp1). Exercise did not reverse these changes. MDSCs were minimally altered by HFD or exercise. Overall, the data from this study suggest that ADSCs decrease in quantity and contribute to adipose ECM remodeling in response to obesity, and exercise training does not significantly impact these outcomes.

Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer.

MALAT1 (metastasis associated lung adenocarcinoma transcript1) is a conserved long non-coding RNA, known to regulate gene expression by modulating transcription and post-transcriptional pre-mRNA processing of a large number of genes. MALAT1 expression is deregulated in various tumors, including breast cancer. However, the significance of such abnormal expression is yet to be fully understood. In this study, we demonstrate that regulation of aggressive breast cancer cell traits by MALAT1 is not predicted solely based on an elevated expression level but is context specific. By performing loss- and gain-of-function studies, both under in vitro and in vivo conditions, we demonstrate that MALAT1 facilitates cell proliferation, tumor progression and metastasis of triple-negative breast cancer (TNBC) cells despite having a comparatively lower expression level than ER or HER2-positive breast cancer cells. Furthermore, MALAT1 regulates the expression of several cancer metastasis-related genes, but displays molecular subtype specific correlations with such genes. Assessment of the prognostic significance of MALAT1 in human breast cancer (n=1992) revealed elevated MALAT1 expression was associated with decreased disease-specific survival in ER negative, lymph node negative patients of the HER2 and TNBC molecular subtypes. Multivariable analysis confirmed MALAT1 to have independent prognostic significance in the TNBC lymph node negative patient subset (HR=2.64, 95%CI 1.35- 5.16, p=0.005). We propose that the functional significance of MALAT1 as a metastasis driver and its potential use as a prognostic marker is most promising for those patients diagnosed with ER negative, lymph node negative breast cancer who might otherwise mistakenly be stratified to have low recurrence risk.

FOXC1 Activates Smoothened-Independent Hedgehog Signaling in Basal-like Breast Cancer.

The mesoderm- and epithelial-mesenchymal transition-associated transcription factor FOXC1 is specifically overexpressed in basal-like breast cancer (BLBC), but its biochemical function is not understood. Here, we demonstrate that FOXC1 controls cancer stem cell (CSC) properties enriched in BLBC cells via activation of Smoothened (SMO)-independent Hedgehog (Hh) signaling. This non-canonical activation of Hh is specifically mediated by Gli2. Furthermore, we show that the N-terminal domain of FOXC1 (aa 1-68) binds directly to an internal region (aa 898-1168) of Gli2, enhancing the DNA-binding and transcription-activating capacity of Gli2. FOXC1 expression correlates with that of Gli2 and its targets in human breast cancers. Moreover, FOXC1 overexpression reduces sensitivity to anti-Hedgehog (Hh) inhibitors in BLBC cells and xenograft tumors. Together, these findings reveal FOXC1-mediated non-canonical Hh signaling that determines the BLBC stem-like phenotype and anti-Hh sensitivity, supporting inhibition of FOXC1 pathways as potential approaches for improving BLBC treatment.

A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.

The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of treatments in vivo. The traditional, established protocol has been further fine-tuned to minimize the damage to the animal. Notably, the pectoral muscle layers are teased away rather than simply cut, and the thoracotomy is approached intercostally as opposed to breaking the ribs in a sternotomy, preserving the integrity of the ribcage. With these changes, the overall stress on the animal is decreased. Stem cell therapies aimed to alleviate the damage caused by MIs have shown promise over the years for their pro-angiogenic and anti-apoptotic benefits. Current approaches of delivering cells to the heart surface typically involve the injection of the cells either near the damaged site, within a coronary artery, or into the peripheral blood stream. While the cells have proven to home to the damaged myocardium, functionality is limited by their poor engraftment at the site of injury, resulting in diffusion into the blood stream. This manuscript highlights a procedure that overcomes this obstacle with the use of a cell-encapsulated hydrogel patch. The patch is fabricated prior to the surgical procedure and is placed on the injured myocardium immediately following the occlusion of the left coronary artery. To adhere the patch in place, biocompatible external fibrin glue is placed directly on top of the patch, allowing for it to dry to both the patch and the heart surface. This approach provides a novel adhesion method for the application of a delicate cell-encapsulating therapeutic construct.

Diagnosis of Basal-Like Breast Cancer Using a FOXC1-Based Assay.

BACKGROUND: Diagnosis of basal-like breast cancer (BLBC) remains a bottleneck to conducting effective clinical trials for this aggressive subtype. We postulated that elevated expression of Forkhead Box transcription factor C1 (FOXC1) is a simple and accurate diagnostic biomarker for BLBC. METHODS: Accuracy of FOXC1 expression in identifying BLBC was compared with the PAM50 gene expression panel in gene expression microarray (GEM) (n = 1992) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 349) datasets. A FOXC1-based immunohistochemical (IHC) assay was developed and assessed in 96 archival formalin-fixed, paraffin-embedded (FFPE) breast cancer samples that also underwent PAM50 profiling. All statistical tests were two-sided. RESULTS: A FOXC1-based two-tier assay (IHC +/- qRT-PCR) accurately identified BLBC (AUC = 0.88) in an independent cohort of FFPE samples, validating the accuracy of FOXC1-defined BLBC in GEM (AUC = 0.90) and qRT-PCR (AUC = 0.88) studies, when compared with platform-specific PAM50-defined BLBC. The hazard ratio (HR) for disease-specific survival in patients having FOXC1-defined BLBC was 1.71 (95% CI = 1.31 to 2.23, P < .001), comparable to PAM50 assay-defined BLBC (HR = 1.74, 95% CI = 1.40 to 2.17, P < .001). FOXC1 expression also predicted the development of brain metastasis. Importantly, unlike triple-negative or Core Basal IHC definitions, a FOXC1-based definition is able to identify BLBC in both ER+ and HER2+ patients. CONCLUSION: A FOXC1-based two-tier assay, by virtue of being rapid, simple, accurate, and cost-effective may emerge as the diagnostic assay of choice for BLBC. Such a test could substantially improve clinical trial enrichment of BLBC patients and accelerate the identification of effective chemotherapeutic options for this aggressive disease.

Enriched inhibition of cancer and stem-like cancer cells via STAT-3 modulating niclocelles.

We describe for the first time a therapeutic strategy to target stem-like cancer cells via STAT-3 modulation using a nanomedicine approach. Niclocelle, a niclosamide loaded rigid core mixed micelle, was synthesized from a self-assembled well-defined amphiphilic diblock copolymer and an FDA-approved signal transducer and activator of transcription factor 3. Followed by a rigorous physico-chemical characterization, niclocelles were evaluated biologically for cytotoxicity and apoptosis in human melanoma (C32) and breast cancer (MDA-MB231 and MCF-7) cells. Niclocelles were found to selectively reduce the CD44+ stem cell population in C32 cells via STAT-3 modulation.

Mesenchymal stem cells augment the adaptive response to eccentric exercise.

PURPOSE: The α7ß1 integrin is a transmembrane protein expressed in the skeletal muscle that can link the actin cytoskeleton to the surrounding basal lamina. We have previously demonstrated that transgenic mice overexpressing the α7B integrin in the skeletal muscle (MCK:α7B; α7Tg) mount an enhanced satellite cell and growth response to single or multiple bouts of eccentric exercise. In addition, interstitial stem cells characterized as mesenchymal stem cells (MSCs) accumulate in α7Tg muscle (mMSCs) in the sedentary state and after exercise. The results from these studies prompted us to determine the extent to which mMSC underlie the beneficial adaptive responses observed in α7Tg skeletal muscle after exercise. METHODS: mMSCs (Sca-1CD45) were isolated from α7Tg mice, dye-labeled, and intramuscularly injected into adult wild type recipient mice. After injection of mMSCs or saline, mice remained sedentary (SED) or were subjected to eccentric exercise training (TR) (downhill running) on a treadmill (three times per week) for 2 or 4 wk. Gastrocnemius-soleus complexes were collected 24 h after the last bout of exercise. RESULTS: mMSCs did not directly fuse with existing fibers; however, mMSCs injection enhanced Pax7 satellite cell number and myonuclear content compared with all other groups at 2 wk after exercise. Mean CSA, percentage of larger caliber fibers (>3000 µm), and grip strength were increased in mMSCs/TR compared with saline/SED and mMSCs/SED at 4 wk. mMSC transplantation did not enhance repair or growth in the absence of exercise. CONCLUSIONS: The results from this study demonstrate that mMSCs contribute to beneficial changes in satellite cell expansion and growth in α7Tg muscle after eccentric exercise. Thus, MSCs that naturally accumulate in the muscle after eccentric contractions may enhance the adaptive response to exercise.