Transcriptional changes in bone marrow stromal cells of patients with heart failure.

It is proposed that patients with heart failure may have not only myocardial dysfunction, but also a reduced regenerative capacity of stem cells. However, very little is known about bone marrow stromal cell (BMSC) characteristics in heart failure and its comorbidities (obesity and/or diabetes). We hypothesized that metabolic alterations associated with the latter will be reflected in altered expression of key genes related to angiogenesis, inflammation, and tissue remodeling in patient-derived BMSCs. We found that BMSCs of heart failure patients with lower body mass index have enhanced expression of genes involved in extracellular matrix remodeling. In particular, body mass index<30 was associated with upregulated expression of genes encoding collagen type I, proteases and protease activators (MMP2, MMP14, uPA), and regulatory molecules (CTGF, ITGß5, SMAD7, SNAIL1). In contrast, these transcript levels did not differ significantly between BMSCs from obese heart failure patients and healthy subjects. Comorbidities (including obesity and diabetes) are known to play role in heart failure progression rate and outcome of the disease. We thus suggest that key molecular targets identified in this study should become the target of the subsequent focused studies. In the future, these targets may find some use in the clinical setting.

Bone marrow- and subcutaneous adipose tissue-derived mesenchymal stem cells: differences and similarities.

Bone marrow (BM) and subcutaneous adipose tissue (Ad) are both considered being prospective sources of MSC for therapeutic applications. However, functional properties and therapeutic efficacy of MSC derived from different tissues of the same patient are still poorly investigated. In our study, BM-MSC and F-MSC cultures from 43 adult donors were evaluated in successive passages for immunophenotype, secretion of VEGF, SDF1, MCP1, IL6 and TGFß1, frequency of colony-forming units (CFU-F), frequency of adipo- and osteo-progenitors (CFU-Ad, CFU-Ost), and for onset of in vitro replicative senescence. We have demonstrated that at early passages (P2-P4 or up to 14-15 in vitro population doublings) BM- and Ad- derived MSC cultures are comparable in such important characteristics as proliferation rate (population doubling time: 3.4±0.2% in BM-MSC, 3±0.3% in F-MSC), clonogenity (CFU-F frequency: 32±5% in BM-MSC, 31±5% in F-MSC), differentiation potential (CFU-Ad frequency: 10.4±2% in BM-MSC, 13±3% in F-MSC; CFU-Ost frequency: 18.5±5.5% in BM-MSC, 18±5% in F-MSC), but differ significantly in abundance of CD146⁺ fraction within the sample (25±5% in BM-MSC, 7±3% in F-MSC) and in a level of VEGF, SDF-1, MCP1 and TGFß1 secretion. We have also demonstrated that BM-MSC enter senescence after P3-4 while most of F-MSC did not show senescence features up to P6-8. Together, these data demonstrate that specific properties of MSC from different sources should be always taken into account, when developing and optimizing the specific protocols for MSC expansion and evaluation for each particular clinical application.