Labeling stem cells with magnetic nanoparticles is a promising technique for in vivo tracking and magnetic targeting of transplanted stem cells, which is critical for improving the therapeutic efficacy of cell therapy. However, conventional endocytic labeling with relatively poor labeling efficiency and a short labeling lifetime has hindered the implementation of these innovative enhancements in stem-cell-mediated regenerative medicine. Herein, we describe an advanced magnetothermal approach to label mesenchymal stem cells (MSCs) efficiently by local induction of heat-enhanced membrane permeability for magnetic resonance imaging (MRI) tracking and targeted therapy of stroke, where biocompatible γ-phase, ferrimagnetic vortex-domain iron oxide nanorings (γ-FVIOs) with superior magnetoresponsive properties were used as a tracer. This approach facilitates a safe and efficient labeling of γ-FVIOs as high as 150 pg of Fe per cell without affecting the MSCs proliferation and differentiation, which is 3.44-fold higher than that by endocytosis labeling. Such a high labeling efficiency not only enables the ultrasensitive magnetic resonance imaging (MRI) detection of sub-10 cells and long-term tracking of transplanted MSCs over 10 weeks but also endows transplanted MSCs with a magnetic manipulation ability in vivo. A proof-of-concept study using a rat stroke model showed that the labeled MSCs facilitated MRI tracking and magnetic targeting for efficient replacement therapy with a significantly reduced dosage of 5 × 10⁴ transplanted cells. The findings in this study have demonstrated the great potential of the magnetothermal approach as an efficient labeling technique for future clinical usage.

中文翻译：

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生物相容性氧化铁纳米环标记间充质干细胞：一种用于细胞追踪和靶向中风治疗的创新磁热方法

用磁性纳米粒子标记干细胞是一种很有前途的体内技术移植干细胞的跟踪和磁性靶向，这对于提高细胞疗法的治疗效果至关重要。然而，标记效率相对较差且标记寿命较短的传统内吞标记阻碍了这些创新增强技术在干细胞介导的再生医学中的实施。在此，我们描述了一种先进的磁热方法，通过局部感应热增强膜通透性来有效标记间充质干细胞 (MSC)，用于磁共振成像 (MRI) 跟踪和中风靶向治疗，其中生物相容性 γ 相、亚铁磁涡旋域具有优异磁响应特性的氧化铁纳米环（γ-FVIOs）被用作示踪剂。这种方法有助于安全有效地标记每个细胞高达 150 pg Fe 的 γ-FVIO，而不影响 MSC 的增殖和分化，比内吞标记高 3.44 倍。如此高的标记效率，不仅可以实现亚10细胞的超灵敏磁共振成像（MRI）检测和移植MSCs长达10周以上的长期跟踪，还赋予移植MSCs磁操作能力体内。使用大鼠中风模型的概念验证研究表明，标记的 MSCs 促进了 MRI 跟踪和磁性靶向，以实现有效的替代治疗，并显着减少 5 × 10 ⁴移植细胞的剂量。本研究的结果证明了磁热方法作为一种有效标记技术的巨大潜力，可用于未来的临床应用。