Lauridsen Henrik, Foldager Casper Bindzus, Hansen Line, Pedersen Michael
Department of Clinical Medicine, Comparative Medicine Lab, Aarhus University, 8200 Aarhus N, Denmark.
Department of Clinical Medicine, Orthopaedic Research Lab, Aarhus University, 8000 Aarhus C, Denmark.
Exp Ther Med. 2018 Apr;15(4):3311-3319. doi: 10.3892/etm.2018.5865. Epub 2018 Feb 14.
Non-invasive methods to track the progress of stem cell therapies are important in the development of future regenerative therapies. Super-paramagnetic iron oxide particles (SPIOs) have previously been applied to track cells using magnetic resonance imaging (MRI) in non-regenerative animal models. To the best of the author's knowledge, the present study investigated for the first time, the feasibility of tracking SPIO labeled cells in an intrinsic regenerative environment, the regenerating limb of the axolotl, and investigated the homing of stem cell-like blastema cells to the regenerative zone. Viability and labeling success of labeled axolotl blastema cells was tested using cell culture and histology. SPIO labeling was performed by intramuscular injections and mapped using MRI. Enhanced permeability and retention (EPR) effects were evaluated in the blastema, liver, heart, kidney and a back muscle. Finally, SPIO/Fluorophore-labeled blastema cells were injected intravascularly and tracked using MRI and fluorescence imaging. It was demonstrated that SPIO labeling had no effect on axolotl cell viability . labeling resulted in an MRI signal alteration during 48 days of regeneration. EPR effect of unbound SPIO was observed only in the liver. MRI tracking revealed increased concentrations of SPIO labeled blastema cells in the liver, kidney and heart, however not the blastema of intravascularly injected axolotls. In conclusion, the results demonstrated that SPIO labeling facilitated non-invasive tracking of injected cells in the regenerating axolotl limb. An early homing mechanism of injected blastema cells to an injury site was not observed.
追踪干细胞疗法进展的非侵入性方法在未来再生疗法的发展中至关重要。超顺磁性氧化铁颗粒（SPIOs）此前已被应用于在非再生动物模型中利用磁共振成像（MRI）追踪细胞。据作者所知，本研究首次调查了在蝾螈再生肢体这一内在再生环境中追踪SPIOs标记细胞的可行性，并研究了干细胞样芽基细胞向再生区域的归巢情况。使用细胞培养和组织学检测了标记的蝾螈芽基细胞的活力和标记成功率。通过肌肉注射进行SPIOs标记，并使用MRI进行定位。在芽基、肝脏、心脏、肾脏和一块背部肌肉中评估了增强渗透与滞留（EPR）效应。最后，将SPIOs/荧光团标记的芽基细胞经血管内注射，并使用MRI和荧光成像进行追踪。结果表明，SPIOs标记对蝾螈细胞活力没有影响。标记在48天的再生过程中导致了MRI信号改变。未结合的SPIOs的EPR效应仅在肝脏中观察到。MRI追踪显示，在肝脏、肾脏和心脏中，SPIOs标记的芽基细胞浓度增加，但在经血管内注射的蝾螈的芽基中未观察到。总之，结果表明，SPIOs标记有助于对蝾螈再生肢体中注射的细胞进行非侵入性追踪。未观察到注射的芽基细胞向损伤部位的早期归巢机制。
