title: Iron sucrose-labeled human mesenchymal stem cells: in vitro multilineage capability and in vivo traceability in a lapine xenotransplantation model.
abstract: For evaluation of cell therapy applications, it is of interest to be able to trace and observe cellular distribution of the transplanted cells. The aim with the study was to examine viability, traceability, and multilineage capability of iron sucrose-labeled mesenchymal stem cells (MSCs) after transplantation into lapine intervertebral discs (IVDs). MSCs were collected from three human donors, age 31-50 years, and IVDs from 12 rabbits, age 3 months. MSCs were isolated from the bone marrow and cultured using standard protocols. Iron sucrose labeling of MSCs was performed in Dulbecco's Modified Eagle's Medium-low glucose with Venofer(®). The iron sucrose-labeled MSCs were differentiated into the adipogenic, osteogenic, and chondrogenic lineages. Results were evaluated using Oil red, von Kossa, Alcian blue, and collagen II (immunohistochemistry). For the animal experiments, iron sucrose-labeled MSCs and nonlabeled MSCs were injected into lapine IVDs (LI-LIV level). After transplantation, at the time points of 1 and 3 months, IVDs were collected and cells were analyzed for cell viability (fluorescence-activated cell sorting). The lapine IVDs were collected and examined for presence of cells positive for iron deposits using Berliner blue staining. Differentiation of the iron sucrose-labeled MSCs into adipogenic (lipid droplets), osteogenic (calcium deposits), and chondrogenic lineage (proteoglycan/collagen II accumulation) (3/3 donors) was observed in vitro. After transplantation, the mean cell viability for iron-labeled MSCs/IVD cells was 99%, for nonlabeled MSCs/IVD cells was 95%, and for control IVD cells was 99% at a time point of 1 month. At a time point of 3 months, mean cell viability was 73% for iron sucrose-labeled MSCs/IVD cells, for nonlabeled MSCs/IVD cells was 77%, and for control IVD cells was 98%. At the time point of 1 month, cells positive for iron deposits were detected sparsely distributed in IVDs (tissue sections) in 4/4 animals and at the time point of 3 months in 4/4 animals. The results indicate that iron sucrose can be used as a cell tracer with a stable detection potential in tissues (histologies). This may be an important evaluation tool for understanding stem cell distribution/function after transplantation into degenerated cartilaginous tissues.
authors.affiliation: 1 Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University , Gothenburg, Sweden .|2 Department of Orthopedics, Sahlgrenska University Hospital , Gothenburg, Sweden .
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papadimitriou
authors.affiliation: 3 Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University , Gothenburg, Sweden .
authors.forename: Susann
authors.initials: S
authors.lastname: Li
authors.affiliation: 1 Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University , Gothenburg, Sweden .|2 Department of Orthopedics, Sahlgrenska University Hospital , Gothenburg, Sweden .
authors.forename: Helena
authors.initials: H
authors.lastname: Barreto Henriksson
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007403:Intervertebral Disc / Q000166:cytology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011817:Rabbits; D014183:Transplantation, Heterologous / Q000379:methods