Charge, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mamma...

Cellular and Molecular Regulation of Muscle Regeneration

Background— Experimental data suggest that bone marrow–derived cells may contribute to the healing of myocardial infarction (MI). For this reason, we analyzed 10 patients who were treated by intracoronary transplantation of autologous, mononuclear bone marrow cells (BMCs) in addition to standard therapy after MI. Methods and Results— After standard therapy for acute MI, 10 patients were transplanted with autologous mononuclear BMCs via a balloon catheter placed into the infarct-related artery during balloon dilatation (percutaneous transluminal coronary angioplasty). Another 10 patients with acute MI were treated by standard therapy alone. After 3 months of follow-up, the infarct region (determined by left ventriculography) had decreased significantly within the cell therapy group (from 30±13 to 12±7%, P=0.005) and was also significantly smaller compared with the standard therapy group (P=0.04). Likewise, infarction wall movement velocity increased significantly only in the cell therapy group (from 2.0±1....

Repair of Infarcted Myocardium by Autologous Intracoronary Mononuclear Bone Marrow Cell Transplantation in Humans

The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection, prompting several clinical trials. Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.

Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts

Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriched hematopoietic stem cells, the so-called side population (SP) cells, into lethally irradiated mice subsequently rendered ischemic by coronary artery occlusion for 60 minutes followed by reperfusion. The engrafted SP cells (CD34–/low, c-Kit+, Sca-1+) or their progeny migrated into ischemic cardiac muscle and blood vessels, differentiated to cardiomyocytes and endothelial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express lacZ widely. Donor-derived cardiomyocytes were found primarily in the peri-infarct region at a prevalence of around 0.02% and were identified by expression of lacZ and α-actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marker shown to be absent on SP cells. Endothelial engraftment was found at a prevalence of around 3.3%, primarily in small vessels adjacent to the infarct. Our results demonstrate the cardiomyogenic potential of hematopoietic stem cells and suggest a therapeutic strategy that eventually could benefit patients with myocardial infarction.

/pdf/regeneration-of-ischemic-cardiac-muscle-and-vascular-316hhyyzvm.pdf

Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process invol...

Satellite Cells and the Muscle Stem Cell Niche

Purpose To evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies. Methods Data from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as ≥50% seizure reduction. Treatment effects on EEG, developmental outcome and the "outcome-predictive" value of various clinical factors were also assessed. Results 50 children (22 boys; mean age 4.5 years±3.55) were included. Mean follow-up was 3.93±2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly ( p =0.014) and a significantly lower rate of epileptic discharges ( p =0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress ( p =0.038). Favourable treatment outcome was associated with a shorter disease duration ( p =0.025) and generalised tonic clonic seizures ( p =0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome. Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate ( p =0.001) and valproate ( p =0.046). Conclusion Despite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development.

Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy--the Austrian experience.

A number of studies have already been undertaken to investigate involvement of oxyradicals in muscle diseases by means of measurements of oxyradical protective enzymes. We investigated o-tyrosine, which is a biomarker for OH radical damage in vivo, in 10 mdx and 10 control mice. We also measured mitochondrial enzymes in muscle homogenates of 10 mdx and 10 control mice. Mdx mice had significantly elevated values for o-tyrosine, succinat-phenacinmetosulfat oxidoreductase. NADH O2 oxidoreductase and cytochrome C oxidoreductase. Our findings confirm the suggestion that elevated oxyradical production occurs in muscular dystrophies with lack of dystrophin. Furthermore, our results demonstrate that OH radical damage does not impair mitochondrial enzyme activities in the mdx mouse.

Oxyradical damage and mitochondrial enzyme activities in the mdx mouse

Auditory evoked potentials in young patients with Down syndrome. Event-related potentials (P3) and histaminergic system.

Study objective : To assess the effect of topiramate (TPM) on body mass index (BMI) in paediatric epilepsy patients and to examine predictors of weight loss. Design : Retrospective, observational study. Setting : University clinic epilepsy outpatient department. Subjects : Patients below age 18 years who received TPM for at least 12 months. Measurements and main results : Changes in BMI (kg/m 2 ) standard deviation scores (S.D.S.) from baseline to the follow-up periods of 12, 24 and 36 months were evaluated. The repeated measures t -test for paired samples, revealed significant decreases for BMI S.D.S. at 12 months ( P =0.004; n =53) and 24 months ( P =0.044; n =35), but no significant decrease at 36 months ( n =21). Analysis of variance revealed a predictor value of sex for BMI S.D.S. at 12 months (females more likely to lose weight; P =0.037) and a predictor value of baseline BMI for BMI S.D.S. at 24 months (patients with a higher baseline BMI were more likely to lose weight; P =0.047). Conclusion : Weight loss is common in paediatric epilepsy patients who receive TPM and is sustained for at least one year. The pattern of weight loss differs according to sex and baseline BMI.

Changes in body mass index during long-term topiramate therapy in paediatric epilepsy patients—a retrospective analysis

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)02848-8.pdf

Effects of transdermal nicotine on cognitive performance in Down's syndrome.

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