Molecular and functional effects of organismal ageing on smooth muscle cells derived from bone marrow mesenchymal stem cells.
OBJECTIVE
Bone marrow-derived smooth muscle cells (BM-SMCs) have high potential as an autologous cell source of vascular progenitors but normal cell function and turnover frequency may decline with age. In this study we set out to study the effects of organismal ageing on the molecular and functional properties of BM-SMCs.


RESULTS
To address this issue, we employed a smooth muscle alpha-actin promoter (alphaSMA) driving expression of enhanced green fluorescence protein (EGFP) to isolate SMCs from bone marrow of neonatal (nBM-SMCs) or adult (aBM-SMCs) sheep and examined their proliferation potential and contractility. Compared with nBM-SMCs, aBM-SMCs exhibited lower clonogenicity and proliferation potential that could be improved significantly by addition of basic fibroblast growth factor. Vascular constructs from aBM-SMCs showed reduced ability to generate force and contract fibrin hydrogels and this function could be partially restored by addition of transforming growth factor-beta1. They also exhibited lower receptor- and non-receptor-mediated vascular contractility and mechanical strength, which was comparable to that of tissue constructs prepared with vascular SMCs from neonatal umbilical veins. In agreement with the contractile properties and mechanical strength of vascular constructs, aBM-SMCs displayed significantly lower expression of alphaSMA, smoothelin, desmin, type I collagen, and tropoelastin transcripts compared with nBM-SMCs.


CONCLUSIONS
Understanding the effects of organismal ageing on BM-SMCs and the properties of the resulting vascular constructs may lead to innovative ways to facilitate application of these cells in the treatment of cardiovascular disease which is especially prevalent in the elderly.
Han
Juhee
J
Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, 908 Furnas Hall, Amherst, NY 14260-4200, USA.
Liu
Jin Yu
JY
Swartz
Daniel D
DD
Andreadis
Stelios T
ST
D000199:Actins / Q000235:genetics; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D016922:Cellular Senescence; D024042:Collagen Type I / Q000235:genetics; D003893:Desmin / Q000235:genetics; D015536:Down-Regulation; D005337:Fibrin / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014333:Tropoelastin / Q000235:genetics; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000199:Actins; D024042:Collagen Type I; D003893:Desmin; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin; D014662:Vasoconstrictor Agents; C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D005337:Fibrin