Microvascular tubes derived from embryonic stem cells sustain blood flow.
Since the introduction of somatic cell nuclear transfer (SCNT), therapeutic cloning has been brought closer to reality. Among the potential applications of therapeutic cloning is therapeutic angiogenesis. Although recent progress has been made with clinical therapeutic angiogenesis, it has met with limited success. One reason for this limitation has been the cell types used to generate the collateral vessels used for shunting around coronary blockages. Consequently, we developed a procedure using the embryonic stem (ES) cell model system to generate microvascular tubes similar to small vessels found in vivo. We then evaluated their ability to graft and sustain blood flow by transplanting them onto enhanced green fluorescent protein (eGFP)-expressing embryonic day-9 (E9) embryo hearts. Microvascular tubes generated from ES cells have not been thoroughly tested for their ability to graft and function within the heart, primarily because of issues including immune rejection of the foreign cells comprising collateral vessels and limited methodologies to prevent teratoma risk. However, because recent therapeutic cloning techniques have provided evidence of diminished risk of immune rejection, we improved the methodology for generating and isolating tubes from ES cells to evaluate their applicability for therapeutic angiogenesis. Here, we demonstrate that microvascular tubes generated from ES cells are capable of grafting onto E9-day embryo hearts and sustaining the flow of blood cells as verified by eGFP-expressing blood cells within non-eGFP ES cell-derived microvascular tubes.
Zhou
Xuan
X
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Gallicano
G Ian
GI
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology* / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D004622:Embryo, Mammalian / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology; D006321:Heart / Q000196:embryology / Q000502:physiology; D006801:Humans; D007797:Laminin; D051379:Mice; D008822:Mice, Transgenic; D011509:Proteoglycans; D013234:Stem Cells / Q000166:cytology*
D018952:Antigens, CD34; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen