Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells.
The success of therapeutic vascularization and tissue engineering will rely on our ability to create vascular networks using human cells that can be obtained readily, can be expanded safely ex vivo, and can produce robust vasculogenic activity in vivo. Here we describe the formation of functional microvascular beds in immunodeficient mice by coimplantation of human endothelial and mesenchymal progenitor cells isolated from blood and bone marrow. Evaluation of implants after 1 week revealed an extensive network of human blood vessels containing erythrocytes, indicating the rapid formation of functional anastomoses within the host vasculature. The implanted endothelial progenitor cells were restricted to the luminal aspect of the vessels; mesenchymal progenitor cells were adjacent to lumens, confirming their role as perivascular cells. Importantly, the engineered vascular networks remained patent at 4 weeks in vivo. This rapid formation of long-lasting microvascular networks by postnatal progenitor cells obtained from noninvasive sources constitutes an important step forward in the development of clinical strategies for tissue vascularization.
Vascular Biology Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Juan M
JM
Melero-Martin
Maria E
ME
De Obaldia
Soo-Young
SY
Kang
Zia A
ZA
Khan
Lei
L
Yuan
Peter
P
Oettgen
Joyce
J
Bischoff
D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D036101:Cord Blood Stem Cell Transplantation; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020286:Pericytes / Q000166:cytology / Q000502:physiology; D044968:Regenerative Medicine; D023822:Tissue Engineering / Q000379:methods*; D014183:Transplantation, Heterologous