The dynamic in vivo distribution of bone marrow-derived mesenchymal stent cells after infusion

Bone marrow-derived mesenchymal stem cells (MSCs) have the potential to dif ferentiate along different mesenchymal lineages including those forming bon e, cartilage, tendon, fat, muscle and marrow stroma that sup ports hematopo iesis. This differentiation potential makes MSCs candidates for cell-based therapeutic strategies for mesenchymal tissue injuries and for hematopoieti c disorders by both local and systemic application. In the present study, r at marrow-derived MSCs were ex vivo culture-expanded, labeled with (111)ln- oxine, and infused into syngeneic rats via intra-artery (i.a.), intravenous (i.v.) and intraperitoneal cavity (i.p.) infusions. In addition, for i.a. and i.v. infusions, a vasodilator, sodium nitroprusside, was administered p rior to the cell infusion and examined for its effect on MSC circulation. T he dynamic distribution of infused MSCs was monitored by real-time imaging using a gamma camera immediately after infusion and at 48 h postinfusion. A fter 48 h, radioactivity in excised organs, including liver, lungs, kidneys , spleen and long bones, was measured in a gamma well counter and expressed as a percentage of injected doses. After both i.a. and i.v. infusion, radi oactivity associated with MSCs was detected primarily in the lungs and then secondarily in the liver and other organs. When sodium nitroprusside was u sed, more labeled MSCs cleared the lungs resulting in a larger proportion d etected in the liver. Most importantly, the homing of labeled MSCs to the m arrow of long bones was significantly increased by the pretreatment with va sodilator. These results indicate multiple homing sites for injected MSCs a nd that the distribution of MSCs can be influenced by administration of vas odilator. Copyright (C) 2001 S. Karger AG,Basel.