Correlation of Circulating CD133+ Progenitor Subclasses with a Mild Phenotype in Duchenne Muscular Dystrophy Patients

Abstract

BackgroundVarious prognostic serum and cellular markers have been identified for many diseases, such as cardiovascular diseases and tumor pathologies. Here we assessed whether the levels of certain stem cells may predict the progression of Duchenne muscular dystrophy (DMD).Methods and FindingsThe levels of several subpopulations of circulating stem cells expressing the CD133 antigen were determined by flow cytometry in 70 DMD patients. The correlation between the levels and clinical status was assessed by statistical analysis. The median (±SD) age of the population was 10.66±3.81 (range 3 to 20 years). The levels of CD133+CXCR4+CD34- stem cells were significantly higher in DMD patients compared to healthy controls (mean±standard deviation: 17.38±1.38 vs. 11.0±1.70; P = 0.03) with a tendency towards decreased levels in older patients. Moreover, the levels of this subpopulation of cells correlated with the clinical condition. In a subgroup of 19 DMD patients after 24 months of follow-up, increased levels of CD133+CXCR4+CD34- cells was shown to be associated with a phenotype characterised by slower disease progression. The circulating CD133+CXCR4+CD34- cells in patients from different ages did not exhibit significant differences in their myogenic and endothelial in vitro differentiation capacity.ConclusionsOur results suggest that levels of CD133+CXCR4+CD34- could function as a new prognostic clinical marker for the progression of DMD.

The Therapeutic Potential of Stimulating Endogenous Stem Cell Mobilization

“…Similar observations have been made with muscular dystrophy where the rate of progression of the disease has been linked to the number of circulating stem cells and for which the number of PBSC is now considered one of the most important predictors of the disease progression (Marchesi et al, 2008). Likewise, the progression of pulmonary arterial hypertension (Diller et al, 2008;Junhui et al, 2008), arthritis (Herbrig et al, 2006;Grisar et al, 2005), atherosclerosis (Zhu et al, 2006 ), lupus erythematosus (Westerweel et al, 2007;Moonen et al, 2007), kidney failure (Choi et al, 2004;Herbrig et al, 2004;Eizawa et al, 2003), migraine , erectile dysfunction (Baumhakel et al, 2007) and other diseases have all been linked to a reduction in the number of PBSC.…”

<p>Rapid and selective mobilization of specific stem cell types after consumption of a polyphenol-rich extract from sea buckthorn berries (<em>Hippophae</em>) in healthy human subjects</p>

“…Likewise, following acute myocardial infarction, individuals with a higher baseline number of circulating stem cells showed a greater ejection fraction 6 months later 79. A link between a lower number of circulating stem cells and the development of degenerative diseases has been established with diabetes,80 cardiovascular diseases,81 atherosclerosis,82,83 Alzheimer’s disease,84,85 rheumatoid arthritis,86,87 pulmonary diseases,88,89 erectile dysfunction,90,91 and muscular dystrophy 92…”

Understanding the Natural Role of Stem Cells in the Body: A New Understanding of Disease Formation?

“…For example, a linear relationship has been documented between the number of circulating stem cells and the various phases of diabetes development, namely impaired fasting glucose, impaired glucose tolerance and insulin-dependent diabetes [21]. Similar observations have been made with cardiovascular diseases [22], atherosclerosis [23], Alzheimer's disease [24], rheumatoid arthritis [25], pulmonary diseases [26], erectile dysfunction [27], and muscular dystrophy [28].…”