Department of Morphology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Cell Transplant. 2010;19(2):219-30. doi: 10.3727/096368909X479677. Epub 2009 Nov 10.
In this study the time course of homing and the body distribution of systemically delivered bone marrow mesenchymal stem cells (BM-MSCs) after myocardial infarction (MI) were evaluated. BM-MSCs were isolated from Wistar rats, expanded in vitro, and their phenotypical characterization was performed by flow cytometer. Rats were randomly divided into three groups: control, sham MI, and MI. BM-MSCs (5 x 10(6)) were labeled with (99m)Tc-HMPAO and injected through the tail vein 7 days after MI. Gamma camera imaging was performed at 5, 15, 30, and 60 min after cell inoculation. Due to the (99m)Tc short half-life, cell migration and location were also evaluated in heart sections using DAPI-labeled cells 7 days after transplantation. Phenotypical characterization showed that BM-MSCs were CD90(+), CD73(+), CD54(+), and CD45(-). Five minutes after (99m)Tc-HMPAO-labeled cell injection, they were detected in various tissues. The cells migrated mainly to the lungs (approximately 70%) and, in small amounts, to the heart, kidneys, spleen, and bladder. The number of cells in the heart and lungs decreased after 60 min. MI markedly increased the amount of cells in the heart, but not in the lungs, during the period of observation (4.55 +/- 0.32 vs. 6.34 +/- 0.67% of uptake in infarcted hearts). No significant differences were observed between control and sham groups. Additionally, 7 days after DAPI-labeled cells injection, they were still detected in the heart but only in infarcted areas. These results suggest that the migration of systemically delivered BM-MSCs to the heart is time dependent and MI specifically increases BM-MSCs homing to injured hearts. However, the systemic delivery is limited by cell entrapment in the lungs.
在这项研究中，评估了骨髓间充质干细胞（BM-MSCs）在心肌梗死（MI）后归巢的时间过程和体内分布。BM-MSCs 从 Wistar 大鼠中分离出来，在体外扩增，并通过流式细胞仪进行表型特征分析。大鼠随机分为三组：对照组、假 MI 组和 MI 组。在 MI 后 7 天，将 5 x 10(6)个 BM-MSCs 用（99m）Tc-HMPAO 标记，并通过尾静脉注射。在细胞接种后 5、15、30 和 60 分钟进行伽马相机成像。由于（99m）Tc 半衰期短，还使用 DAPI 标记的细胞在移植后 7 天评估心脏切片中的细胞迁移和位置。表型特征表明 BM-MSCs 为 CD90(+)、CD73(+)、CD54(+)和 CD45(-)。在（99m）Tc-HMPAO 标记细胞注射后 5 分钟，它们在各种组织中被检测到。细胞主要迁移到肺部（约 70%），少量迁移到心脏、肾脏、脾脏和膀胱。60 分钟后，心脏和肺部的细胞数量减少。MI 在观察期间（梗死心脏中摄取的 4.55 +/- 0.32%与 6.34 +/- 0.67%）明显增加了心脏中的细胞数量，但肺部没有增加。对照组和假 MI 组之间无显著差异。此外，在 DAPI 标记细胞注射后 7 天，仍在心脏中检测到，但仅在梗死区。这些结果表明，系统给予的 BM-MSCs 向心脏的迁移是时间依赖性的，MI 特异性增加了 BM-MSCs 向受损心脏的归巢。然而，全身给药受到细胞在肺部被捕获的限制。
