title: Functional tissue-engineered blood vessels from bone marrow progenitor cells.
abstract: OBJECTIVE
  Stem cells have significant potential for development of cell-based therapeutics for cardiovascular tissue regeneration.
  
  
  METHODS
  We developed a novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using a tissue-specific promoter and fluorescence-activated cell sorting.
  
  
  RESULTS
  As compared to vascular SMC, bone marrow-derived smooth muscle progenitor cells (BM-SMPC) exhibited similar morphology, showed higher proliferation potential and expressed several SMC markers including alpha-actin, calponin, myosin heavy chain, smoothelin, caldesmon and SM22. When embedded in fibrin hydrogels, BM-SMPC contracted the matrix and displayed receptor- and non-receptor-mediated contractility, indicating that BM-SMPC can generate force in response to vasoreactive agonists. We also prepared tissue-engineered blood vessels from BM-SMPC and BM-derived endothelial cells and implanted them into the jugular veins of lambs. As early as five weeks post-implantation, grafted tissues displayed a confluent endothelial layer overlaying the medial layer in which BM-SMPC were aligned circumferentially and synthesized significant amounts of collagen. In contrast to previous results with vascular SMC, BM-SMPC synthesized high amounts of elastin that was organized in a fibrillar network very similar to that of native vessels.
  
  
  CONCLUSIONS
  Our results suggest that BM-SMPC may be useful in studying SMC differentiation and have high potential for development of cell therapies for the treatment of cardiovascular disease.
authors.affiliation: Bioengineering Laboratory, 908 Furnas Hall, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
authors.forename: Jin Yu
authors.initials: JY
authors.lastname: Liu
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Swartz
authors.forename: Hao Fan
authors.initials: HF
authors.lastname: Peng
authors.forename: Sylvia F
authors.initials: SF
authors.lastname: Gugino
authors.forename: James A
authors.initials: JA
authors.lastname: Russell
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
mesh_terms: D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D001696:Biomechanical Phenomena; D001808:Blood Vessels / Q000502:physiology / Q000637:transplantation; D002148:Calmodulin-Binding Proteins / Q000032:analysis / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D004549:Elastin / Q000032:analysis / Q000096:biosynthesis; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007601:Jugular Veins / Q000601:surgery; D008840:Microfilament Proteins / Q000032:analysis / Q000378:metabolism; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D032390:Myoblasts, Smooth Muscle / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000199:Actins; D015415:Biomarkers; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C100762:SMTN protein, human; C051615:transgelin; D004549:Elastin; D018995:Myosin Heavy Chains