Contractile smooth muscle cells derived from hair-follicle stem cells.
OBJECTIVE
We hypothesized that hair-follicle stem cells can differentiate toward smooth contractile muscle cells, providing an autologous cell source for cardiovascular tissue regeneration.


RESULTS
Smooth muscle progenitor cells (SMPCs) were obtained from ovine hair follicles using a tissue-specific promoter and fluorescence-activated cell sorting. Hair-follicle smooth muscle progenitor cells (HF-SMPCs) expressed several markers of vascular smooth muscle including alpha-actin, calponin, myosin heavy chain (MHC), caldesmon, smoothelin, and SM22. HF-SMPCs were highly proliferative and showed high clonogenic potential without any signs of chromosomal abnormalities as evidenced by karyotype analysis. HF-SMPCs compacted fibrin hydrogels to a similar extent as vascular smooth muscle cells from ovine umbilical veins (V-SMCs), indicating the development of the force-generating machinery. In addition, cylindrical tissue equivalents prepared with HF-SMPCs displayed significant contractility in response to vasoactive agonists including KCl and the thromboxane A2 mimetic U46619, suggesting that these cells had developed receptor and non-receptor-mediated pathways of contractility. Finally, transforming growth factor-beta1 promoted differentiation of HF-SMPCs toward a mature SMC phenotype as suggested by increased expression of MHC and enhanced matrix compaction.


CONCLUSIONS
Our results suggest that hair follicles may be an easily accessible, autologous, and rich source of functional SMPC for cardiovascular tissue engineering and regenerative medicine.
Liu
Jin Yu
JY
Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, 908 Furnas Hall, North Campus, Amherst, NY 14260, USA.
Peng
Hao Fan
HF
Andreadis
Stelios T
ST
D000199:Actins / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012756:Sheep; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000096985:Calponins
D000199:Actins; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D049452:Green Fluorescent Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018995:Myosin Heavy Chains; D053773:Transforming Growth Factor beta1; D000096985:Calponins; C485184:enhanced green fluorescent protein; C051615:transgelin