Tachibana Yoichi, Enmi Jun-ichiro, Agudelo Carlos A, Iida Hidehiro, Yamaoka Tetsuji
Department of Biomedical Engineering and ‡Department of Investigative Radiology, National Cerebral and Cardiovascular Center Research Institute , Suita, Osaka 565-8565, Japan.
Bioconjug Chem. 2014 Jul 16;25(7):1243-51. doi: 10.1021/bc400463t. Epub 2014 Jun 20.
Noninvasive in vivo imaging of transplanted stem cells is an effective method to clarify the mechanisms involved in stem cell transplantation therapy. We labeled rat mesenchymal stem cells (MSCs) with water-soluble magnetic resonance imaging (MRI) contrast agent poly(vinyl alcohol)-gadolinium (PVA-Gd) in order to ascertain the fate of transplanted MSCs in vivo. PVA-Gd was retained and localized in the cytosolic compartment of MSCs for a longer period of time. The effect of PVA-Gd labeling on MSC proliferation was much less than that of the commercially available contrast agent ProHance, and the labeled MSCs were found to have osteoblastic differentiation ability. To study the MSC lifetime in vivo, MSCs were seeded and trapped in the cytocompatible three-dimensional porous scaffolds of Spongel and transplanted. The MRI signal attributed to MSCs was eliminated from the transplanted site in 14 days. Because free PVA-Gd was rapidly eliminated from the site, this signal reduction indicated MSC death in the transplantation site. The low efficiency of MSC transplantation for ischemic tissue may be due to their short lifetime, making it important to develop highly effective stem cell transplantation systems that address cell number, injection position, and cell formulation (suspension, sheet, and aggregates). Our cell survival tracking system would be a very powerful tool to this end and would be applicable in clinical cell therapies.
对移植干细胞进行无创体内成像，是阐明干细胞移植治疗相关机制的有效方法。我们用水溶性磁共振成像（MRI）造影剂聚乙烯醇-钆（PVA-Gd）标记大鼠间充质干细胞（MSC），以确定体内移植MSC的命运。PVA-Gd在MSC的胞质区室中保留并定位较长时间。PVA-Gd标记对MSC增殖的影响远小于市售造影剂普美显，且发现标记的MSC具有成骨分化能力。为研究MSC在体内的存活时间，将MSC接种并捕获在具有细胞相容性的三维多孔Spongel支架中并进行移植。移植部位归因于MSC的MRI信号在14天内消失。由于游离的PVA-Gd从该部位迅速消除，这种信号降低表明移植部位的MSC死亡。MSC对缺血组织移植效率低可能是由于其存活时间短，因此开发解决细胞数量、注射位置和细胞制剂（悬浮液、薄片和聚集体）问题的高效干细胞移植系统很重要。为此，我们的细胞存活追踪系统将是一个非常强大的工具，并且将适用于临床细胞治疗。
