Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy.
We investigated the kinetics of human mesenchymal stem cells (MSCs) after intravascular administration into SCID mouse cremaster vasculature by intravital microscopy. MSCs were injected into abdominal aorta through left femoral artery at two different concentrations (1 x 10(6) or 0.2 x 10(6) cell). Arterial blood velocity decrease by 60 and 18% 1 min after high/low dose MSCs injection respectively. The blood microcirculation was interrupted after 174+/-71 and 485+/-81 s. Intravital microscopy observation and histopathologic analysis of cremaster muscles indicated MSCs were entrapped in capillaries in both groups. 40 and 25% animals died of pulmonary embolism respectively in both high and low MSCs dose groups, which was detected by histopathologic analysis of the lungs. Intraarterial MSCs administration may lead to occlusion in the distal vasculature due to their relatively large cell size. Pulmonary sequestration may cause death in small laboratory animals. MSCs should be used cautiously for intravascular transplantation.
Furlani
Dario
D
Department of Cardiac Surgery, Medical Faculty, University of Rostock Schillingallee 35, 18055 Rostock, Germany.
Ugurlucan
Murat
M
Ong
LeeLee
L
Bieback
Karen
K
Pittermann
Erik
E
Westien
Ingeborg
I
Wang
Weiwei
W
Yerebakan
Can
C
Li
Wenzhong
W
Gaebel
Ralf
R
Li
Ren-ke
RK
Vollmar
Brigitte
B
Steinhoff
Gustav
G
Ma
Nan
N
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001160:Arterioles / Q000473:pathology / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000502:physiology; D048429:Cell Size; D006801:Humans; D007269:Injections, Intra-Arterial; D007511:Ischemia; D008168:Lung / Q000098:blood supply / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008853:Microscopy / Q000379:methods; D018482:Muscle, Skeletal / Q000098:blood supply; D011655:Pulmonary Embolism / Q000209:etiology* / Q000473:pathology; D013923:Thromboembolism / Q000209:etiology* / Q000473:pathology