1] Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA [2] Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Mol Ther. 2014 Jan;22(1):160-8. doi: 10.1038/mt.2013.221. Epub 2013 Sep 25.
It has been hypothesized that mesenchymal stem cells (MSCs) home to sites of injury. Nevertheless, efficient delivery of MSCs to target organs and description of their ultimate fate remain major challenges. We provide evidence that intra-arterially (IA) injected MSCs selectively engraft from the circulation as perivascular cells in the bone marrow (BM) after a localized radiation injury. Luciferase-expressing MSCs, derived from a conditionally immortalized clone (BMC-9) representing a pure population of cells, were arterially delivered into mice irradiated in one leg. Cell distribution was measured by bioluminescent imaging and final destination assessed by luciferase immunolocalization. IA injections resulted in engraftment only in the irradiated leg where cells localize and proliferate abluminal to the BM vasculature, a phenomenon not replicated with intravenous injections or with IA injections of kidney cells harvested from the same donor used for MSCs. Furthermore, MSCs harvested from the engrafted marrow and serially transplanted retain the ability to selectively engraft at sites of injury. This study demonstrates that MSCs can serially engraft at sites of injury from the circulation, that they reside in the perivascular space, and that arterial delivery is more efficient than venous delivery for cell engraftment.
人们推测间充质干细胞（MSCs）会归巢到损伤部位。然而，将 MSCs 有效递送到靶器官并描述其最终归宿仍然是主要挑战。我们提供的证据表明，在局部放射损伤后，经动脉内（IA）注射的 MSCs 会选择性地从循环中作为血管周细胞定植于骨髓（BM）。来自条件永生化克隆（BMC-9）的表达荧光素酶的 MSCs，代表了纯细胞群体，通过动脉内输注到一条腿照射的小鼠体内。通过生物发光成像测量细胞分布，并通过荧光素酶免疫定位评估最终归宿。IA 注射仅在照射的腿部产生定植，细胞定位于 BM 血管腔的外侧并增殖，静脉注射或从用于 MSC 的相同供体收获的肾细胞的 IA 注射均未复制此现象。此外，从植入骨髓中收获并连续移植的 MSCs 保留在损伤部位选择性定植的能力。这项研究表明，MSCs 可以从循环中连续定植到损伤部位，它们位于血管周空间，并且动脉内递送比静脉内递送更有利于细胞定植。
