title: Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation.
abstract: Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [(99m)Tc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole-body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.
authors.affiliation: Department of Biomedical Engineering Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Fangjing
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Saada
authors.initials: S
authors.lastname: Eid
authors.affiliation: Orthopedic Surgery Department at the Baylor College of Medicine, Houston, TX 77030.
authors.forename: James E
authors.initials: JE
authors.lastname: Dennis
authors.affiliation: Department of Oncology, Sidney Kimmel Cancer Center, Baltimore, MD 21287.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
authors.affiliation: Department of Pediatrics, The Ohio State University, Columbus, OH 43205; Department of Pediatrics, The Ohio State University, Columbus, OH 43205; Department of Pediatrics, The Ohio State University, Columbus, OH 43205.
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Auletta
authors.affiliation: Host Defense Program, Hematology/Oncology/Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, OH 43205.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lee
keywords: Arterial injection; Biodistribution; Graft-versus-host disease; Mesenchymal stromal cell; Radionuclide imaging