Functional tissue-engineered blood vessels from bone marrow progenitor cells.
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.
Liu
Jin Yu
JY
Bioengineering Laboratory, 908 Furnas Hall, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
Swartz
Daniel D
DD
Peng
Hao Fan
HF
Gugino
Sylvia F
SF
Russell
James A
JA
Andreadis
Stelios T
ST
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*
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