Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
Department of Geology and Environmental Science, University of Pittsburgh, Pittsburgh, PA, USA.
Sci Rep. 2016 May 18;6:26271. doi: 10.1038/srep26271.
Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new "bio-mimicry" method by making use of the "in-vivo environment" of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 ± 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin-protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 ± 7.2 μm to 19.5 ± 5.2 μm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies.
间充质干细胞(MSCs)是用于细胞治疗和再生医学的主要干细胞之一。体内细胞磁共振成像(MRI)跟踪对于再生医学至关重要,它可以验证移植的细胞是否到达了目标部位。细胞 MRI 与超顺磁氧化铁(SPIO)造影剂相结合是一种有效的细胞跟踪方法。在这里,我们报告了一种新的“仿生”方法,利用 MSCs 的“体内环境”来制备天然 MSCs,从而(i)可以恢复培养的 MSCs 的吞噬活性,并可以对体外培养的 MSCs 进行 Ferumoxytol 标记,目前 Ferumoxytol 是唯一经 FDA 批准用于人体的 SPIO 纳米颗粒。使用我们的新方法,培养 7 天的 MSCs 恢复了摄取 Ferumoxytol 的能力,并表现出 2.50 ± 0.50 pg/MSC 的细胞内铁浓度,与使用 Ferumoxytol-肝素-鱼精蛋白纳米复合物获得的浓度相当;(ii)细胞可以重新调整到更接近天然的大小,从 32.0 ± 7.2 μm 减少到 19.5 ± 5.2 μm。我们的方法可以非常有用地扩展 MSCs 并进行 Ferumoxytol 标记,而无需转染剂和/或电穿孔,从而可以在临床前和临床研究中通过 MRI 进行细胞跟踪。