title: Functional properties of bone marrow derived multipotent mesenchymal stromal cells are altered in heart failure patients, and could be corrected by adjustment of expansion strategies.
abstract: BACKGROUND
  Bone marrow multipotent mesenchymal stromal cells (BM-MMSC) considered as a prospective substrate for cell therapy applications, however adult stem cells could be affected by donor-specific factors: age, gender, medical history. Our aim was to investigate how HF affects the functional properties of BM-MMSC.
  
  
  METHODS
  BM-MMSC from 10 healthy donors (HD), and 16 donors with chronic HF were evaluated for proliferative activity, ability to differentiate, replicative senescence, expression of genes that affect regeneration and fibrosis. The effect of culturing conditions on efficiency of BM-MMSC expansion was determined.
  
  
  RESULTS
  HF-derived BM-MMSC demonstrated early decrease of proliferative activity and upregulation of genes that control both, regeneration and fibrosis: Tgf-β pathway, synthesis of ECM, remodeling enzymes, adhesion molecules. We assume that these effects were related to increase of frequency of myofibroblast-like CD146+/SMAα+ CFU-F in HF samples; (ii) low seeding density and hypoxia resulted in predominant purification and expansion of CD146+/SMAα- CFU-Fs. (iii) the activity of NPs system was downregulated in HF BM-MMSC;
  
  
  CONCLUSIONS
  downregulation of NP signaling in combination with upregulation of Tgf-β pathway in BM-MMSC would result in pro-fibrotic phenotype and make these cells non-effective for therapeutic applications; the corrections in culturing strategy resulted in 2(3)-2(7) increase of expansion efficiency.
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Renata I
authors.initials: RI
authors.lastname: Dmitrieva
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.|St. Petersburg State Polytechnical University, Branch of Medical Physics and Bioengineering, Russia.
authors.forename: Alla V
authors.initials: AV
authors.lastname: Revittser
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Klukina
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Sviryaev
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Ludmila S
authors.initials: LS
authors.lastname: Korostovtseva
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Kostareva
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Andrey Yu
authors.initials: AY
authors.lastname: Zaritskey
authors.affiliation: Federal Almazov Medical Research Centre, St. Petersburg, Russia.
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Shlyakhto
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D015687:Cell Hypoxia; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D016922:Cellular Senescence; D005355:Fibrosis; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000378:metabolism; D010641:Phenotype; D012038:Regeneration; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D045265:Natriuretic Peptides