Intra-arterial Administration of Placenta-Derived Decidual Stromal Cells to the Superior Mesenteric Artery in the Rabbit: Distribution of Cells, Feasibility, and Safety

Abstract

Selective administration of mesenchymal stromal cells to the mesenteric arteries is a potential technique to overcome pulmonary trapping and increase the density of transplanted cells in extensive mural inflammation of the intestine, such as in inflammatory bowel disease and graft-versus-host disease. We injected 5 × 10(6) (111)In-oxine-labeled human decidual stromal cells (DSCs) to the rabbit superior mesenteric artery (SMA) using clinical routine catheters guided by an angiographical system under sterile conditions. We used longitudinal single-photon emission tomography at 6 h and at 1, 2, and 5 days to assess trafficking and distribution of DSCs. We used digital subtraction angiography, computed tomography, and hematoxylin and eosin stainings to determine biodistribution of cells and to assess safety end points. We found that selective injection of human DSCs to the rabbit SMA does not result in acute embolic complications. Furthermore, we found that IV administration resulted in extensive retention of the radiolabeled DSCs in the lungs, corroborating previous studies on pulmonary trapping. In sharp contrast, selective injections to the SMA resulted in uptake distributed in the intestine supplied by the SMA and in the liver, indicating that this approach could significantly increase the fraction of injected DSCs reaching the target tissue.

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

“…Therefore, renal intraarterial MSC infusion limits off-target engraftment, leading to efficient MSC delivery to the kidneys. Similar results were found after selective intraarterial infusion into the superior mesenteric artery regarding the intestine distribution of MSCs [58], and the selective intraarterial limb infusion [59,60], with MSCs distributed in the target area and a small quantity of MSCs in the rest of the organs.…”

Preclinical Toxicity Evaluation of Clinical Grade Placenta-Derived Decidua Stromal Cells

“…Before treating patients, we injected DSCs to rats, as reported in this article and in rabbits (32) and found it to be safe with no side effects. Subsequently, we treated patients with acute and chronic GvHD, hemorrhagic cystitis and acute respiratory distress syndrome (30, 33, 41, 42).…”

“…We previously reported on the good safety and efficacy of DSCs in treatment of GvHD and HC following HSCT (29, 30) as well as in experimental setting (31, 32). When employed at the typical low clinical cell doses, DSCs demonstrated a safe toxicity profile and no side effects in the clinical setting (33) and in an animal model of BMT and GvHD (31).…”

Evaluation of different routes of administration and biodistribution of human amnion epithelial cells in mice

“…Non-invasive imaging techniques are designed for tracking the transplanted cells and to determine their bio-distribution. Bio-distribution studies were performed with different cell types including embryonic stem cells, hepatocytes and mesenchymal stromal cells with different reporter markers such as near infra-red dye (NiR), 111-Indium labeling and magnetic resonance imaging (MRI) (59)(60)(61)(62)(63)(64). For better understanding of hAEC, a bio-distribution study was published by our group recently (65).…”