Use Of Therapeutic Interventions Research Articles

Walking among doctors and patients. Stories and reflections.

The clinician - the doctor who treats sick people - should be able to establish a good human relationship with his or her patients and their family; should be able to reach a diagnosis even in patients with rare diseases, or atypical presentations - or should refer the patient to a senior colleague; and should be able to recommend the best treatment (or no treatment at all). And he - or she - should be able to draw these abilities from the "deliberate practice" according to Ericsson, i.e. from the combination of experience with reflection - not, or with much lesser strength, from the medical literature as suggested by Evidence-Based Medicine. The diagnosis is often an easy task, i.e. by pattern recognition or recognizing a frequent illness script - "fast thinking" in the vocabulary of Kahneman; or a difficult task, sometimes very difficult for rare diseases or atypical presentations - "slow thinking" of Kahneman. The decisions about the use of therapeutic interventions, whether for individuals or entire healthcare systems, should be based on the totality of the available evidence. The idea that evidence can be reliably or usefully placed in "hierarchies" is illusory, and the pedestal deserved to the RCT is inappropriate.

A class of their own: exploring the nondeacetylase roles of class IIa HDACs in cardiovascular disease.

Histone deacetylases (HDACs) play integral roles in many cardiovascular biological processes ranging from transcriptional and translational regulation to protein stabilization and localization. There are 18 known HDACs categorized into 4 classes that can differ on the basis of substrate targets, subcellular localization, and regulatory binding partners. HDACs are classically known for their ability to remove acetyl groups from histone and nonhistone proteins that have lysine residues. However, despite their nomenclature and classical functions, discoveries from many research groups over the past decade have suggested that nondeacetylase roles exist for class IIa HDACs. This is not surprising given that class IIa HDACs have, for example, relatively poor deacetylase capabilities and are often shuttled in and out of nuclei upon specific pathological and nonpathological cardiac events. This review aims to consolidate and elucidate putative nondeacetylase roles for class IIa HDACs and, where possible, highlight studies that provide evidence for their noncanonical roles, especially in the context of cardiovascular maladies. There has been great interest recently in exploring the pharmacological regulators of HDACs for use in therapeutic interventions for treating cardiovascular diseases and inflammation. Thus it is of interest to earnestly consider nonenzymatic and or nondeacetylase roles of HDACs that might be key in potentiating or abrogating pathologies. These noncanonical HDAC functions may possibly yield new mechanisms and targets for drug discovery.

Elevated background noise in adult attention deficit hyperactivity disorder is associated with inattention.

BackgroundInattention and distractibility are core symptoms of attention deficit hyperactivity disorder (ADHD). Still the neuronal organization is largely unknown. Previously we studied the electrophysiological activity of a distinct neuronal network—the retina—and found no change in stimulus-driven neural activity in patients with ADHD. However there is growing evidence for an elevated non stimulus-driven neural activity, or neuronal background noise, as underlying pathophysiological correlate. To further examine the biological bases that might underlie ADHD and problems with inattention, we performed a new analysis to test the hypothesis of an elevated background noise as underlying neuronal correlate for ADHD and problems with inattention in humans. A direct measure of background noise in patients with ADHD has not been described yet.MethodsThe retinal background noise was assessed based on pattern electroretinogram (PERG) data in 20 unmedicated ADHD patients and 20 healthy controls. The PERG is an electrophysiological measure for retinal ganglion cell function. ADHD severity was assessed by interview and questionnaire.ResultsNoise amplitude was significantly higher (138%) in patients with ADHD compared to the control group (p = 0.0047). Noise amplitude correlated significantly with psychometric measures for ADHD (CAARS) especially inattention (r = 0.44, p = 0.004).ConclusionsThe data provide evidence that an elevated background noise is associated with symptoms of inattention in ADHD and support the use of therapeutic interventions that reduce noise and distraction in patients with ADHD.

InSPAL: A Novel Immersive Virtual Learning Programme.

In this paper we introduce The Interactive Sensory Program for Affective Learning (InSPAL) a pioneering virtual learning programme designed for the severely intellectually disabled (SID) students, who are having cognitive deficiencies and other sensory-motor handicaps, and thus need more help and attention in overcoming their learning difficulties. Through combining and integrating interactive media and virtual reality technology with the principles of art therapy and relevant pedagogical techniques, InSPAL aims to strengthen SID students' pre-learning abilities, promote their self-awareness, decrease behavioral interferences with learning as well as social interaction, enhance their communication and thus promote their quality of life. Results of our study show that students who went through our programme were more focused, and the ability to do things more independently increased by 15%. Moreover, 50% of the students showed a marked improvement in the ability to raise their hands in response, thus increasing their communication skills. The use of therapeutic interventions enabled a better control to the body, mind and emotions, resulting a greater performance and better participation.

The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice

ObjectiveParenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. Materials/methodsSix groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. ResultsAll groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. ConclusionThese results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation.

Brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood. The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus. The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions. The study findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.

NO TEMPORAL EFFECT ON DISABILITY IN MULTIPLE SCLEROSIS

It has been suggested that prognosis for multiple sclerosis (MS) has improved over time. This may have occurred as an effect of modified phenotype, changing patient demographics, improved case ascertainment...

Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity

The inadequacy to replace acetaminophen (APAP) with a more effective analgesic continues its use in therapeutic interventions, upholding the risk of hepatotoxicity. Depletion of glutathione reserves by a metabolic intermediate of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), is the major reason. The current study presents the combinatorial effect of metformin, a biguanide, in ameliorating the APAP toxicity. HepG2 cells were used for in vitro studies and MTT and LDH leakage assays were used for viability assessment. 10 μM of metformin improved the cell viability and membrane integrity of cells treated with a high concentration (20 mM) of acetaminophen. Intracellular antioxidant enzymes and reduced glutathione were significantly increased in cells co-administrated with metformin and acetaminophen. A decrease in apoptosis induction and ROS generation was evident by fluorescent microscopy analysis. Flow cytometry showed a quantitative improvement in cell viability. RT–PCR analysis showed an increased expression of Nrf2 genes along with inhibition of BACH 1 in cells treated with metformin and acetaminophen. The expression of the genes encoding antioxidant responsive elements such as glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione cysteine synthase (GCS) was exponentially increased which possibly leads to increased glutathione synthesis and hepatoprotection. Overall results provide new insights regarding pharmacological potential of metformin as a hepatoprotective agent against the toxicity of acetaminophen.

Neuroprotection of microRNA in neurological disorders (Review).

MicroRNAs (miRNAs) are small, endogenous, non-coding RNA molecules that function as post-transcriptional regulators of gene expression by imperfect base-pairing with the 3'-untranslated regions of their target mRNAs. Altered expression of numerous miRNAs has been shown to be extensively involved in the pathogenesis of various diseases and cancers. Additionally, the specific expression of miRNAs in the nervous system has indicated that miRNAs are critical for the occurrence and development of neurological diseases. Increasing evidence has shown that specific miRNAs target the expression of particular proteins that are significant in the disease pathogenesis. Therefore, miRNA-mediated regulation may be important in the occurrence and development of neurological diseases and may function as a novel biomarker and tool for clinical therapy. In the present study, the significance of miRNAs is reviewed in a number of neurological disorders and the possibility of their use in therapeutic interventions is evaluated.

The use of fibroblast growth factor 23 testing in patients with kidney disease.

The emergence of fibroblast growth factor 23 as a potentially modifiable risk factor in CKD has led to growing interest in its measurement as a tool to assess patient risk and target therapy. This review discusses the analytical and clinical challenges faced in translating fibroblast growth factor 23 testing into routine practice. As for other bone mineral markers, agreement between commercial fibroblast growth factor 23 assays is poor, mainly because of differences in calibration, but also, these differences reflect the variable detection of hormone fragments. Direct comparison of readout from different assays is consequently limited and likely hampers setting uniform fibroblast growth factor 23-directed targets. Efforts are needed to standardize assay output to enhance clinical use. Fibroblast growth factor 23 is robustly associated with cardiovascular and renal outcomes in patients with CKD and adds value to risk assessments based on conventional risk factors. Compared with most other mineral markers, fibroblast growth factor 23 shows better intraindividual temporal stability, with minimal diurnal and week-to-week variability, but substantial interindividual variation, maximizing discriminative power for risk stratification. Conventional therapeutic interventions for the CKD-mineral bone disorder, such as dietary phosphate restriction and use of oral phosphate binders or calcimimetics, are associated with variable efficacy at modulating circulating fibroblast growth factor 23 concentrations, like they are for other mineral metabolites. Dual therapy with dietary phosphate restriction and noncalcium-based binder use achieves the most consistent fibroblast growth factor 23-lowering effect and seems best monitored using an intact assay. Additional studies are needed to evaluate whether strategies aimed at reducing levels or antagonizing its action have beneficial effects on clinical outcomes in CKD patients. Moreover, a better understanding of the mechanisms driving fibroblast growth factor 23 elevations in CKD is needed to inform the use of therapeutic interventions targeting fibroblast growth factor 23 excess. This evidence must be forthcoming to support the use of fibroblast growth factor 23 measurement and fibroblast growth factor 23-directed therapy in the clinic.

Does premarital education decrease or increase couples’ later help-seeking?

Interventions intended to prevent relationship distress are expected to enhance relationship satisfaction and, in turn, reduce the need for later couples counseling. We test this prediction against an alternative possibility: participation in preventive interventions may operate as a gateway for later help-seeking, paradoxically increasing receipt of later couples counseling. A cross-sectional study of 2,126 married individuals examined whether participation in premarital education covaried inversely or directly with couples counseling. Consistent with the gateway hypothesis, receiving premarital education covaried with an increased likelihood of receiving couples counseling. The association between receipt of premarital education and pursuit of couples counseling was moderated by demographic indicators, with the association being stronger for African Americans and for individuals with lower incomes and less formal education. Encouraging the use of premarital interventions may increase the use of therapeutic interventions later in the relationship, especially among high-risk populations.

EPA-0866 – Using an individualized neuroimaging approach to investigate effects of psychotherapy in depression. First results of the zurich depression study

Research on neurobiologic underpinnings of psychotherapy in depression is still sparse, particularly in psychodynamic oriented research. At present, there is insufficient data on neurobiologic parameters that could allow a targeted use of therapeutic interventions. One reason for this is the methodological difficulty of investigating complex and individual phenomena relevant to the psychotherapeutic process with functional neuroimaging techniques. The Zurich Depression Study takes up this strong research need developing a pioneer study design. An individualized neuroimaging paradigm was developed based on the MIPQS (Maladaptive Interpersonal Q-Sort (Zimmermann et al., accepted), a self report instrument derived from the OPD-2 axis interpersonal relations (Operationalized Psychodynamic Diagnosis 2, Arbeitskreis OPD, 2006). Visual stimuli were developed and tested that systematically illustrate interpersonal behaviour patterns (Interpersonal Relations Picture Set (IRPS)). They are employed in an individualized fMRI experiment. The experiment was validated with ten healthy study participants Preliminary results suggest that the experimental paradigm is an accurate method to be employed in psychotherapy research with depressed patients. Specific hemodynamic activation patterns observed during the individualized fMRI task involve brain regions commonly identified as playing a role in emotion processing and autobiographic memory. A final overview of these first results will be given at the EPA 2014 congress.

Endoscopic Retrograde Cholangiopancreatography in the Pediatric Population Is Safe and Efficacious

Endoscopic retrograde cholangiopancreatography (ERCP) is increasingly being used in the evaluation and management of biliary and pancreatic disorders in children. The aim of this study was to review the pediatric ERCP experience of a large academic referral center affiliated with a tertiary care children's hospital. This is a retrospective review of medical records, endoscopic and operative reports, and radiography of those patients ages 0 to 21 years who underwent ERCP for any indication between 1993 and 2011 at a tertiary referral center affiliated with a large urban pediatric hospital. ERCP technical success was defined as cannulation of the desired duct. Serious adverse events included bleeding, perforation, pancreatitis, or death. Four hundred twenty-nine ERCPs were performed on 296 patients. The mean age was 14.9 ± 4.8 years (3 months-21 years); 51.1% were boys. Patients with a history of previous liver transplant comprised 13.1% (56) of all ERCPs. Abnormal liver chemistries or suspected choledocholithiasis accounted for half of the indications. A therapeutic intervention was performed in 64.1%. Technical success was achieved in 95.2% of ERCPs. Serious adverse events occurred in 7.7%. Pediatric ERCP is highly efficacious in the pediatric population, with the rates of technical success and use of therapeutic interventions mirroring those in adults. There is a low overall rate of serious adverse events. The overall efficacy and safety support the performance of pediatric ERCP by experienced endoscopists at high-volume centers.

‘I Divide Life into Different Dimensions, one Mental and one Physical, to be Able to Handle Life, you Know?’ Subjective Accounts of the Content of Psychotic Symptoms

Previous research indicates that the content of psychotic symptoms is of significant importance for the individual who experiences them. However, there are limitations concerning the use of self-report instruments for capturing experiences that are of highly personal nature. The aim of this study was to provide a deeper understanding of how individuals with psychosis make sense of the content of their psychotic symptoms. Semi-structured interviews were conducted with 12 individuals, some of whom were experiencing active symptoms and some of whom had experienced symptoms within the last 12 months. The interviews explored the individuals' understanding of psychotic symptoms in terms of the content and the possible meaning of the content. All participants were patients at a unit specializing in psychosis. The study applied interpretive phenomenological analyses to highlight the subjective understanding of the content of psychotic symptoms. Interpersonal experiences were a consistent theme in participants' understanding of the content of their psychotic symptoms. Grandiose content was understood as being related to lack of relationships and helplessness, whereas harassing content was related to experiences of being abused. Commanding content was linked to emotional consequences of intrusive relationships and to distressing life events. Supportive content was viewed as a substitute for real-life persons. These results support previous findings suggesting that the content of psychotic symptoms is related to interpersonal experiences. The study highlights the importance of validating the patient's own knowledge and interpretations of symptoms.

A Population Approach to the Rational Use of Therapeutic Interventions

THE EVIDENCE BASE Most developed countries, and an increasing number of developing ones, aspire to provide universal access to healthcare for their citizens. All, however, have resource constraints and must inevitably make priorities in determining their coverage decisions. Consequently, when making decisions about the availability of therapeutic interventions both cost effectiveness, as well as clinical effectiveness, must be taken into account by decision-makers.

Detection of BRAF and KRAS mutations in DNA released by tumors in peripheral blood by an advanced digital droplet PCR.

e22056 Background: Cell-free tumor DNA (cftDNA) is released into the circulation and its recovery from plasma is a non-invasive alternative to tumor biopsy for applications related to molecular profiling. A potential use in therapeutic interventions is the periodic monitoring of cftDNA for the identification of molecular changes associated with resistance to target-specific treatments or when the mutational status in tumor tissue is not available. Methods: Samples (6 ml) of peripheral blood were drawn from patients with colorectal (CRC, n= 19) and thyroid (n= 1) cancers and melanoma (n= 8). CRC tumors were KRAS wild-type (n= 3) or carried the BRAF V600E (n= 6), KRAS G12D (n= 9) and G12V (n= 4) mutations. All melanomas and the thyroid cancer carried the BRAF V600E mutation. DNA was extracted from plasma with QIAamp Circulating Nucleic Acid Kit to recover DNA fragments of ≤1000 bp. PCR amplification was carried out with a QX100 ddPCR System (Bio-Rad) on 20 μL-samples containing cftDNA and TaqMan probes for BRAF V600E (1799T>A), KRAS G12D (35G>A) and G12V (35G>T) labeled with FAM/VIC. Samples were then loaded into a droplet reader, which discriminates the difference in fluorescence amplitudes on the basis of target gene amplification. Results: The concordance between mutations in tumors (T) and plasma (P) for BRAF V600E was: melanomas 8 T vs. 6 P; thyroid cancer 1 T vs. 0 P; CRC 6 T vs 3 P. Concerning KRAS in CRC the results were: G12D 9 T vs. 7 P, G12V 4 T vs. 0 P. Overall, the percentage of concordant samples were: V600E 60%, G12D 77,8%, G12V 0%. Interestingly, in 2 patients with wild-type KRAS tumor, the G12D and G12V mutations were found in plasma. Conclusions: ddPCR is a third-generation PCR technique for highly sensitive detection of DNA fragments. Detection of mutations in cftDNA by advanced technological platforms has important applications in the monitoring of patients for the occurrence of secondary mutations, amplifications and expansion of cell clones that render their tumors resistant to target-specific anticancer agents, unraveling the resistant phenotype before the clinical progression of the disease. Acknowledgments: this study was funded in part by MIUR/PRIN 2011-2012 (Rome, Italy).

Let's Get SEERious: More Accurate Staging With Consequent High Management Impact Is Not Just Stage Migration

issue in heath care resourcing. Although individuals with non–smallcell lung carcinoma (NSCLC), their physicians, and third-party health care payers deserve reassurance that the increasing use of positron emission tomography (PET) is beneficial, we have significant concerns regarding the methodology applied and, consequently, the validity of the resulting conclusions. Most importantly, we feel that all-cause survival is an inappropriate primary end point for judging the benefits of a diagnostic test. This parameter ignores the potential of a superior investigation to guide more efficient and appropriate use of therapeutic interventions and to induce changes in management that may influence quality of life or progressionfree survival in particular patient subgroups without necessarily affecting long-term survival. This is particularly relevant in a disease like NSCLC in which current therapeutic interventions have suboptimal efficacy and are associated with substantial cost and toxicity. Nevertheless, because it has been previously established that the dominant effect of applying PET to NSCLC staging is the detection of unrecognized metastases, 2,3 a logical assumption must be that palliative therapies would be more frequently applied with increasing use of PET. If PET inappropriately upstages patients and results in patients’ denial of potentially curative therapies, overall survival should logically deteriorate. The authors’ finding that all-cause survival did not change significantly with the increasing use of PET supports a conclusion that PET may reduce morbidity associated with futile therapies without negatively affecting overall patient outcomes. We believe that if any conclusion can be reached, their data thus support rather than repudiate the utility of PET in NSCLC. As there is currently no curative therapy available for stage 4 NSCLC, it is unreasonable to expect a large change in overall survival with the application of PET. The earliest study end point of 2-year overall survival used by the authors is, we contend, too long to reliably detect improvements in survival associated with better selection and delivery of palliative treatments in such patients. In our own recently published prospective trial of PET/computed tomography in NSCLC, the median survival of patients with stage 4 disease on PET was less than a year and almost all patients in this stage group died within 2 years. 4 Moreover, patients who died as an immediate complication of futile therapy would also not be detected because the study excluded patients who died within 2 months.

Importance of serum basal tryptase levels in children with insect venom allergy

The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 μg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 μg/l (2.5-4.0)] and healthy control subjects [2.9 μg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 μg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.

Use of a care bundle in the emergency department for acute exacerbations of chronic obstructive pulmonary disease: a feasibility study

AimTo determine the efficacy and usefulness of a chronic obstructive pulmonary disease (COPD) care bundle designed for the initial management of acute exacerbations of COPD and to assess whether it improves quality of care and provides better outcomes.IntroductionThe level of care provided in the emergency department (ED) for COPD exacerbations varies greatly, and there is a need for a more systematic, consistent, evidence-based quality improvement approach to improve outcomes and costs.MethodsA prospective before and after study was carried out in a university teaching hospital. Fifty consecutive patients were identified in the ED with COPD exacerbations and their management was reviewed. Following the education of ED staff and the implementation of a COPD care bundle, the outcome for 51 consecutive patients was analyzed. This COPD care bundle consisted of ten elements considered essential to the management of COPD exacerbations and was scored 0–10 according to the number of items on the checklist implemented correctly.ResultsFollowing implementation, the mean bundle score out of 10 improved from 4.6 to 7 (P<0.001). There was a significant decrease in the unnecessary use of intravenous corticosteroids from 60% to 32% (P=0.003) and also a marked improvement in the use of oxygen therapy, with appropriate treatment increasing from 76% to 96% (P=0.003). Prophylaxis for venous thromboembolism also improved from 54% to 73% (P=0.054). The 30-day readmission rate did not significantly improve.ConclusionThe use of a bundle improves the delivery of care for COPD exacerbations in the ED. There is more appropriate use of therapeutic interventions, especially oxygen therapy and intravenous corticosteroids.

The emerging biology of muscle stem cells: Implications for cell‐based therapies

Cell-based therapies for degenerative diseases of the musculature remain on the verge of feasibility. Myogenic cells are relatively abundant, accessible, and typically harbor significant proliferative potential ex vivo. However, their use for therapeutic intervention is limited due to several critical aspects of their complex biology. Recent insights based on mouse models have advanced our understanding of the molecular mechanisms controlling the function of myogenic progenitors significantly. Moreover, the discovery of atypical myogenic cell types with the ability to cross the blood-muscle barrier has opened exciting new therapeutic avenues. In this paper, we outline the major problems that are currently associated with the manipulation of myogenic cells and discuss promising strategies to overcome these obstacles.