title: Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model.
abstract: OBJECTIVE
  Bone marrow mononuclear cells (BM-MNCs) and bone marrow-derived mesenchymal stem stromal cells (BM-MSCs) could have therapeutic potential for numerous conditions, including ischemia-related injury. Cells transplanted intravascularly may become entrapped in the lungs, which potentially decreases their therapeutic effect and increases the risk for embolism.
  
  
  METHODS
  Twelve pigs were divided into groups of 3 and received (99m)Tc- hydroxymethyl-propylene-amine-oxime-labeled autologous BM-MNCs or allogeneic BM-MSCs by either intravenous (IV) or intra-arterial (IA) transplantation. A whole body scan and single photon emission computed tomography/computed tomography (SPECT/CT) were performed 8 h later, and tissue biopsies were collected for gamma counting. A helical CT scan was also performed on 4 pigs to detect possible pulmonary embolism, 2 after IV BM-MSC injection and 2 after saline injection.
  
  
  RESULTS
  The transplantation route had a greater impact on the biodistribution of the BM-MSCs than the BM-MNCs. The BM-MNCs accumulated in the spleen and bones, irrespective of the administration route. The BM-MSCs had relatively higher uptake in the kidneys. The IA transplantation decreased the deposition of BM-MSCs in the lungs and increased uptake in other organs, especially in the liver. Lung atelectases were frequent due to mechanical ventilation and attracted transplanted cells. CT did not reveal any pulmonary embolism.
  
  
  CONCLUSIONS
  Both administration routes were found to be safe, but iatrogenic atelectasis might be an issue when cells accumulate in the lungs. The IA administration is effective in avoiding pulmonary entrapment of BM-MSCs. The cell type and administration method both have a major impact on the acute homing.
authors.affiliation: Department of Surgery, Oulu University Hospital, Oulu, Finland. Electronic address: tuomas.makela@oulu.fi.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mäkelä
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Takalo
authors.affiliation: Department of Surgery, Oulu University Hospital, Oulu, Finland.
authors.forename: Oiva
authors.initials: O
authors.lastname: Arvola
authors.affiliation: Department of Surgery, Oulu University Hospital, Oulu, Finland.
authors.forename: Henri
authors.initials: H
authors.lastname: Haapanen
authors.affiliation: Department of Surgery, Oulu University Hospital, Oulu, Finland.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Yannopoulos
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Ahvenjärvi
authors.affiliation: Department of Anaesthesiology, Oulu University Hospital, Oulu, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kiviluoma
authors.affiliation: Finnish Red Cross Blood Service, Research and Cell Therapy Services, Helsinki, Finland.
authors.forename: Erja
authors.initials: E
authors.lastname: Kerkelä
authors.affiliation: Finnish Red Cross Blood Service, Research and Cell Therapy Services, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Nystedt
authors.affiliation: Department of Surgery, Oulu University Hospital, Oulu, Finland.
authors.forename: Tatu
authors.initials: T
authors.lastname: Juvonen
authors.affiliation: Department of Anatomy and Cell Biology, Medical Research Center, University of Oulu, Oulu, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002634:Chemotaxis, Leukocyte; D005260:Female; D007261:Infusions, Intra-Arterial / Q000379:methods; D007275:Injections, Intravenous; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D023421:Models, Animal; D001261:Pulmonary Atelectasis / Q000000981:diagnostic imaging / Q000209:etiology; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging / Q000209:etiology; D012449:Safety; D013552:Swine; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
keywords: biodistribution; imaging; stem cells