Intra-arterial catheter system to repeatedly deliver mesenchymal stem cells in a rat renal failure model.
BACKGROUND
Mesenchymal stem cell therapy in renal failure is rarely used because of low rates of cell engraftment after systemic delivery. Repeated intra-arterial cell administration may improve results; however, no current delivery method permits repeated intra-arterial infusions in a rat model. In this study, we developed an intra-arterial delivery system for repeated stem cell infusion via the aorta, catheterizing the left femoral artery to the suprarenal aorta under fluoroscopic guidance in rats with adenosine-induced renal failure.


METHODS
First, we compared our intra-arterial catheter system (C group, n = 3) with tail vein injection (V group, n = 3) for engraftment efficacy, using mesenchymal stem cells from luciferase transgenic rats. Rats were infused with the cells and euthanized the following day; we performed cell-tracking experiments using a bioluminescence imaging system to assess the distribution of the infused cells. Second, we assessed the safety of the system over a 30-day period in a second group of six rats receiving infusions every 7 days.


RESULTS
Cells infused through our delivery system efficiently engrafted into the kidney, compared with peripheral venous infusion. In five of the six rats in the safety study, the delivery system remained patent for at least 9 days (range, 9-24 days). Complications became evident only after 10 days.


CONCLUSIONS
Our intra-arterial catheter system was effective in delivering cells to the kidney and permitted repeated injection of cells.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.|Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.|Department of Urology, St. Marianna University School of Medicine, Kawasaki, Japan.
Yuichi
Y
Katsuoka
Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.
Hiroki
H
Ohta
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.|Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.|Department of Urology, St. Marianna University School of Medicine, Kawasaki, Japan.
Eisuke
E
Fujimoto
Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.
Luna
L
Izuhara
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Shinya
S
Yokote
Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.
Sho
S
Kurihara
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.|Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.
Shuichiro
S
Yamanaka
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.|Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.
Susumu
S
Tajiri
Department of Urology, St. Marianna University School of Medicine, Kawasaki, Japan.
Tatsuya
T
Chikaraish
Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan.
Hirotaka J
HJ
Okano
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan. tyokoo@jikei.ac.jp.
Takashi
T
Yokoo
D000818:Animals; D002408:Catheters, Indwelling; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation*; D011917:Rats, Inbred Lew; D051437:Renal Insufficiency / Q000628:therapy*
Intra-arterial; Mesenchymal stem cell therapy; Rat model