Implantation of capillary structure engineered by optical lithography improves hind limb ischemia in mice.
We previously reported a novel optical lithographic technique for the construction of a capillary network consisting of endothelial cells. To investigate the feasibility of clinical application in the treatment of ischemic diseases, capillary structures were formed on scaffolds made from amniotic membrane (AM) and implanted into mice. The capillary network remained in place for at least 5 days and blood perfusion through the implanted capillaries was histologically detected in an ear flap model. Moreover, blood was observed flowing through the capillary network implanted in abdominal subcutaneous tissue of mice at 5 days after insertion. Implantation of the AM capillary structure into the ischemic hind limbs of mice significantly increased reperfusion compared with controls (AM only). Blood flow was restored in the ischemic limbs to the level of corresponding nonischemic limbs as early as 9 days after surgical implantation. The treatment reversed ischemic symptoms, and ambulatory impairment was significantly improved. Thus, the implantation of a capillary network engineered ex vivo could have therapeutic potential for ischemic diseases.
Akahori
Taichi
T
Department of Cellular Physiological Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Kobayashi
Akiko
A
Komaki
Motohiro
M
Hattori
Hideshi
H
Nakahama
Ken-Ichi
K
Ichinose
Shizuko
S
Abe
Mayumi
M
Takeda
Satoru
S
Morita
Ikuo
I
D000650:Amnion / Q000378:metabolism; D000818:Animals; D001807:Blood Vessel Prosthesis; D002196:Capillaries / Q000473:pathology*; D002417:Cattle; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D055620:Optical Phenomena; D019919:Prosthesis Implantation / Q000379:methods*; D012039:Regional Blood Flow; D023822:Tissue Engineering / Q000379:methods*