Noninvasive Tracking and Regenerative Capabilities of Transplanted Human Umbilical Cord-Derived Mesenchymal Stem Cells Labeled with I-III-IV Semiconducting Nanocrystals in Liver-Injured Living Mice
Noninvasive Tracking and Regenerative Capabilities of Transplanted Human Umbilical Cord-Derived Mesenchymal Stem Cells Labeled with I-III-IV Semiconducting Nanocrystals in Liver-Injured Living Mice
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DOI：
10.1021/acsami.8b19953
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发表时间：
2019-03-06
影响因子：
9.5
通讯作者：
Murugan, Arumugam Vadivel
中科院分区：
文献类型：
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作者：
Chetty, Shashank Shankar;Praneetha, Selvarasu;Murugan, Arumugam Vadivel
急性肝损伤是由于肝细胞普遍死亡而引起的严重综合征，迫切需要进行肝移植。由于缺乏健康的供体，这种方法肯定会受到阻碍。在这方面，基于干细胞的再生疗法在修复损伤的组织和器官以用于医学应用方面是有吸引力的。然而，了解移植干细胞在活体动物模型中的迁移、植入和再生能力至关重要。这是第一次，我们展示了近红外（NIR）荧光CuInS2-ZnS纳米晶体（CIZ-NC）的脐带来源的间充质干细胞（MSC）的快速标记，以开发创新的纳米生物缀合物（MSCs-CIZS-NBCs），表现出98%的标记效率。在nanobioconjugate合成之前，通过两步，热注入，快速和低成本的国内微波-微波（MW-R）的方法在6分钟内制备的原始的CIX-NC。合成的CIX-NC显示高的光致发光量子产率（类似于88%）和长寿命（23.4 μ s）。与未标记的MSC相比，MSCs-CIZS纳米生物缀合物显示出优异的生物相容性而不影响干细胞性，如通过细胞活力、免疫表型（CD44（+）、CD105（+）、CD90（+））多谱系特异性基因表达以及分化成脂肪细胞、骨细胞和软骨细胞所证实的。体内荧光示踪分析显示，尾静脉注射后的MSCs-CIZS-NBCs最初被捕获在肺中，并在2h内逐渐植入损伤的肝脏。MSCs-CIZS-. NBCs的再生潜力通过由肝细胞周围的门静脉、胆管和肝动脉组成的门静脉系统的更新来证实。因此，没有明显的炎症，坏死，或凋亡观察到对乙酰氨基酚（APAP）诱导的肝损伤BALB/c小鼠模型移植后3天，证实了使用激光扫描共聚焦显微镜和组织病理学和血液学分析。因此，我们创新的NIR荧光MSCs-CIZS-NBCs提供了一种非侵入性技术，用于在急性肝损伤动物模型中无创跟踪移植的MSC，用于未来的图像引导细胞治疗。
Acute liver injury is a critical syndrome ascribed to prevalent death of hepatocytes and imperatively requires liver transplantation. Such a methodology is certainly hampered due to the deficit of healthy donors. In this regard, stem cell-based regenerative therapies are attractive in repairing injured tissues and organs for medical applications. However, it is crucial to understand the migration, engraftment, and regeneration capabilities of transplanted stem cells in the living animal models. For the first time, we demonstrate rapid labeling of umbilical cord-derived mesenchymal stem cells (MSCs) with near-infrared (NIR)-fluorescent CuInS2-ZnS nanocrystals (CIZS-NCs) to develop innovative nanobioconjugates (MSCs-CIZS-NBCs) that exhibit 98% labeling efficiency. Before nanobioconjugate synthesis, the pristine CIZS-NCs were prepared via a two-step, hot-injection, rapid and low-cost domestic-microwave-refluxing (MW-R) method within 6 min. The as-synthesized CIZS-NCs display high photoluminescence quantum yield (similar to 88%) and long-lived lifetime (23.4 mu s). In contrast to unlabeled MSCs, the MSCs-CIZS nanobioconjugates show excellent biocompatibility without affecting the sternness, as confirmed by cell viability, immunophenotyping (CD44(+), CD105(+),CD90(+)) multi-lineage-specific gene expressions, and differentiation into adipocytes, osteocytes, and chondrocytes. The in vivo fluorescence tracking analyses revealed that the MSCs-CIZS-NBCs after tail-vein injection were initially trapped in the lungs and gradually engrafted in the injured liver within 2 h. The regeneration potential of MSCs-CIZS-.NBCs was confirmed via renewal of the portal tract composed of portal veins, bile ducts, and hepatic arteries around the hepatocytes. Consequently, no apparent inflammations, necrosis, or apoptosis was observed in the acetaminophen (APAP)-induced liver-injured BALB/c mice model over 3 days after transplantation, as corroborated using laser-scanning confocal microscopy and histopathological and hematological analyses. Hence, our innovative NIR-fluorescent MSCs-CIZS-NBCs offer an off-the-self technology for noninvasive tracking of transplanted MSCs in an acute-liver-injured animal model for future image-guided cell-therapies.