Development of a new method for endovascular aortic repair: combination therapy of cell transplantation and stent grafts with a drug delivery system.
BACKGROUND
Endovascular aortic repair by stent grafts (S/Gs) has been developed as a less invasive treatment for aortic aneurysms. However, some aneurysmal cavities can remain without organization, causing re-expansion. We demonstrated previously that transplantation of a cell combination (myoblasts and fibroblasts) promoted thrombus organization in a rat model. We also developed basic fibroblast growth factor (bFGF) slow-delivery S/Gs coated with elastin and impregnated with bFGF. Here, we evaluated the effects of cell transplantation combined with bFGF slow release on canine thoracic aortic aneurysmal sacs after S/Gs repair.


RESULTS
Thoracic aortic aneurysms were surgically created with jugular vein patches in 15 beagles. Myoblasts and fibroblasts of autologous skeletal muscle were isolated and cultured for cell transplantation. The S/Gs had 6 holes and produced endoleaks in the excluded cavities. Collagen gel (gel group, n=5) or a mixture of skeletal myoblasts and fibroblasts with collagen gel (cell group, n=5) were injected into the aneurysmal sacs excluded by the S/Gs. We also studied the effects of combined therapy of bFGF slow-release S/Gs and cell transplantation (hybrid group, n=5). After 14 days, histological analyses revealed that the excluded aneurysmal cavities of the gel group were filled with fresh thrombus, whereas the excluded cavities in the cell-transplanted groups were occupied by organized tissue. The percentages of the organized areas relative to the excluded cavities, evaluated by Masson's trichrome staining, were 18.1+/-4.0%, 52.6+/-4.0%, and 77.1+/-6.9% in the gel, cell, and hybrid groups, respectively. Collagen fibers had already appeared, and increased numbers of alpha-smooth muscle actin-positive cells were observed in the hybrid group.


CONCLUSIONS
Cell transplantation accelerated thrombus organization. Moreover, slow release of bFGF enhanced the effects of cell transplantation. Cell transplantation into unorganized spaces may improve the outcomes of endovascular treatments of aortic aneurysms.
Kajimoto
Masaki
M
Department of Thoracic and Cardiovascular Surgery, Mie University, Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan.
Shimono
Takatsugu
T
Hirano
Koji
K
Miyake
Yoichiro
Y
Sawada
Yasuhiro
Y
Kato
Noriyuki
N
Hirata
Hitoshi
H
Imanaka-Yoshida
Kyoko
K
Nishikawa
Masakatsu
M
Yoshida
Toshimichi
T
Shimpo
Hideto
H
Horiuchi
Takashi
T
Miyamoto
Keiichi
K
D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D001777:Blood Coagulation; D002404:Catheterization; D002478:Cells, Cultured / Q000637:transplantation; D003094:Collagen / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004285:Dogs; D004343:Drug Implants; D004549:Elastin; D004867:Equipment Design; D004868:Equipment Failure; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D005347:Fibroblasts / Q000637:transplantation*; D005355:Fibrosis; D005782:Gels; D006801:Humans; D020007:Implants, Experimental / Q000009:adverse effects; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000637:transplantation*; D011138:Polytetrafluoroethylene; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013193:Stainless Steel; D015607:Stents / Q000009:adverse effects; D014182:Transplantation, Autologous
D004343:Drug Implants; D005782:Gels; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D013193:Stainless Steel; D011138:Polytetrafluoroethylene; D003094:Collagen; D004549:Elastin