Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells.
Tissue engineering may offer patients new options when replacement or repair of an organ is needed. However, most tissues will require a microvascular network to supply oxygen and nutrients. One strategy for creating a microvascular network would be promotion of vasculogenesis in situ by seeding vascular progenitor cells within the biopolymeric construct. To pursue this strategy, we isolated CD34(+)/CD133(+) endothelial progenitor cells (EPC) from human umbilical cord blood and expanded the cells ex vivo as EPC-derived endothelial cells (EC). The EPC lost expression of the stem cell marker CD133 but continued to express the endothelial markers KDR/VEGF-R2, VE-cadherin, CD31, von Willebrand factor, and E-selectin. The cells were also shown to mediate calcium-dependent adhesion of HL-60 cells, a human promyelocytic leukemia cell line, providing evidence for a proinflammatory endothelial phenotype. The EPC-derived EC maintained this endothelial phenotype when expanded in roller bottles and subsequently seeded on polyglycolic acid-poly-l-lactic acid (PGA-PLLA) scaffolds, but microvessel formation was not observed. In contrast, EPC-derived EC seeded with human smooth muscle cells formed capillary-like structures throughout the scaffold (76.5 +/- 35 microvessels/mm(2)). These results indicate that 1) EPC-derived EC can be expanded in vitro and seeded on biodegradable scaffolds with preservation of endothelial phenotype and 2) EPC-derived EC seeded with human smooth muscle cells form microvessels on porous PGA-PLLA scaffolds. These properties indicate that EPC may be well suited for creating microvascular networks within tissue-engineered constructs.
Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
Xiao
X
Wu
Elena
E
Rabkin-Aikawa
Kristine J
KJ
Guleserian
Tjorvi E
TE
Perry
Yutaka
Y
Masuda
Fraser W H
FW
Sutherland
Frederick J
FJ
Schoen
John E
JE
Mayer
Joyce
J
Bischoff
D000071916:AC133 Antigen; D020341:Absorbable Implants; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism / Q000502:physiology; D001808:Blood Vessels; D002455:Cell Division; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D005312:Fetal Blood; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019344:Lactic Acid; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D011091:Polyesters; D011100:Polyglycolic Acid; D011108:Polymers; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D023822:Tissue Engineering
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; C000606023:PROM1 protein, human; D010455:Peptides; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)