The Dynamic in vivo Distribution of Bone Marrow-Derived Mesenchymal Stem Cells after Infusion

Abstract

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.

Stem Cells and Cell Therapies in Lung Biology and Diseases: Conference Report

“…Prockop considered paradigm one to be highly unlikely to account for MSC beneficial effects in lung diseases. Although intravenously administered MSCs are initially "trapped" in the lung, imaging studies have failed to document significant long-term pulmonary engraftment of MSCs (74,75). In the lung, he believes that paradigm three is most likely, and the identification of factors secreted by MSCs may enable the development of novel specific protein-or small molecule-based therapies for ALI.…”

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…infusion mostly in lungs and secondarily in liver and other organs. 44 More detailed studies in three baboons (two using autologous and one allogeneic MSC) and using the green fluorescent protein retroviral construct showed that gastrointestinal tissues harboured high concentrations of transgene per microgram of DNA. Additional tissues including kidney, lung, liver, thymus, and skin were also found to contain relatively high amounts of DNA equivalents.…”

Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration

“…Our approach of delivering human MSCs intraperitoneally may have helped minimise access of these cells to the CNS [2]. Certainly using either antibody staining for human nuclear antigen or the fluorescence of GFP-labelled cells we found barely detectable levels of CNS infiltration, and yet observed a pronounced therapeutic impact of these cells on EAE severity.…”