Assessment of the Tissue Distribution of Transplanted Human Endothelial Progenitor Cells by Radioactive Labeling

Abstract

Background-Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular functionafter experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs. Methods and Results-Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [ 111 In]indium oxine. EPCs (10 6 ) were injected in athymic nude rats 24 hours after myocardial infarction (nϭ8) or sham operation (nϭ8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, Ϸ70% of the radioactivity was localized in the spleen and liver, with only Ϸ1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02Ϯ0.19 in sham-operated animals to 2.03Ϯ0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69Ϯ1.54 in sham-operated animals to 4.70Ϯ1.55 (PϽ0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone. Conclusions-Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy. (Circulation.

MicroRNA‐181a Regulates Local Immune Balance by Inhibiting Proliferation and Immunosuppressive Properties of Mesenchymal Stem Cells

“…Under stress conditions, MSCs decrease local inflammation and participate in tissue repair and regeneration by secreting cytokines, chemokines, and extracellular matrix proteins [3,4]. Previous data from our group and others demonstrated the immunosuppressive and anti-inflammatory effects of MSCs in the treatment of several animal disease models, including autoimmune diseases [5][6][7].…”

Cardiac Effects of Experimental Intravenous Bone Marrow Cell Transplantation after Myocardial Infarction

“…However, even radioactive labeled endothelial progenitor cells had been given intravenously and could be detected afterwards in different organs including the myocardium hours later. 12) Crucial for an effective stem cell-mediated repair of infarcted myocardium seems to be several signalling factors like SDF-1, TNF-α or VEGF, which are involved in stem cell mobilization and chemotaxis, as well as in cardio-and angiogenesis.…”

Stem Cell Monitoring with a Direct or Indirect Labeling Method

“…There are two main classes of cell labeling methods for molecular imaging: the direct and indirect labeling methods. For in vivo visualization, transplanted cells need to be directly labeled ex vivo with radiotracers [12][13][14][15][16][17][18], nanoparticles, or quantum dots [19][20][21][22], or they have to express a reporter gene by indirect labeling [23,24]. Direct labeling was performed prior to cell transplantation with 99m Tc-hexamethylpropylenamine oxime ( 99m Tc-HMPAO) or 111 In-oxine [25].…”