The Dynamic in vivo Distribution of Bone Marrow-Derived Mesenchymal Stem Cells after InfusionGao J. · Dennis J.E. · Muzic R.F. · Lundberg M. · Caplan A.I.
aSkeletal Research Center, Department of Biology and bDepartment of Radiology, Case Western Reserve University, Cleveland, Ohio, USA
Bone marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate along different mesenchymal lineages including those forming bone, cartilage, tendon, fat, muscle and marrow stroma that supports hematopoiesis. This differentiation potential makes MSCs candidates for cell-based therapeutic strategies for mesenchymal tissue injuries and for hematopoietic disorders by both local and systemic application. In the present study, rat marrow-derived MSCs were ex vivo culture-expanded, labeled with 111In-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 prior to the cell infusion and examined for its effect on MSC circulation. The dynamic distribution of infused MSCs was monitored by real-time imaging using a gamma camera immediately after infusion and at 48 h postinfusion. After 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, radioactivity associated with MSCs was detected primarily in the lungs and then secondarily in the liver and other organs. When sodium nitroprusside was used, more labeled MSCs cleared the lungs resulting in a larger proportion detected in the liver. Most importantly, the homing of labeled MSCs to the marrow of long bones was significantly increased by the pretreatment with vasodilator. These results indicate multiple homing sites for injected MSCs and that the distribution of MSCs can be influenced by administration of vasodilator.
Dr. Arnold I. Caplan
Skeletal Research Center, Department of Biology
Case Western Reserve University
2080 Adelbert Road, Cleveland, OH 44106-7080 (USA)
Tel. +1 216 368 3562, Fax +1 216 368 4077
Accepted after revision: July 25, 2000
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 1, Number of References : 47
Cells Tissues Organs (in vivo, in vitro)
Founded 1945 as Acta Anatomica
Vol. 169, No. 1, Year 2001 (Cover Date: 2001)Formerly Acta Anatomica
Journal Editor: H.-W. Denker, Essen; A.W. English, Atlanta, Ga.
ISSN: 1422–6405 (print), 1422–6421 (Online)
For additional information: http://www.karger.com/journals/cto