In vivo ectopic implantation model to assess human mesenchymal progenitor cell potential.
Clinical interest on human mesenchymal progenitor cells (hMPC) relies on their potential applicability in cell-based therapies. An in vitro characterization is usually performed in order to define MPC potency. However, in vitro predictions not always correlate with in vivo results and thus there is no consensus in how to really assess cell potency. Our goal was to provide an in vivo testing method to define cell behavior before therapeutic usage, especially for bone tissue engineering applications. In this context, we wondered whether bone marrow stromal cells (hBMSC) would proceed in an osteogenic microenvironment. Based on previous approaches, we developed a fibrin/ceramic/BMP-2/hBMSCs compound. We implanted the compound during only 2 weeks in NOD-SCID mice, either orthotopically to assess its osteoinductive property or subcutaneously to analyze its adequacy as a cell potency testing method. Using fluorescent cell labeling and immunohistochemistry techniques, we could ascertain cell differentiation to bone, bone marrow, cartilage, adipocyte and fibrous tissue. We observed differences in cell potential among different batches of hBMSCs, which did not strictly correlate with in vitro analyses. Our data indicate that the method we have developed is reliable, rapid and reproducible to define cell potency, and may be useful for testing cells destined to bone tissue engineering purposes. Additionally, results obtained with hMPCs from other sources indicate that our method is suitable for testing any potentially implantable mesenchymal cell. Finally, we propose that this model could successfully be employed for bone marrow niche and bone tumor studies.
Unidad de Biotecnología Celular, Instituto de Investigación en Enfermedades Raras, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km. 2.200, Majadahonda, Madrid, Spain.
Ander
A
Abarrategi
Raquel
R
Perez-Tavarez
Miguel Angel
MA
Rodriguez-Milla
Isabel
I
Cubillo
Francisca
F
Mulero
Arantzazu
A
Alfranca
Jose Luis
JL
Lopez-Lacomba
Javier
J
García-Castro
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002516:Ceramics / Q000494:pharmacology; D005337:Fibrin / Q000494:pharmacology; D006801:Humans; D020007:Implants, Experimental; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010641:Phenotype; D054457:Tissue Scaffolds / Q000737:chemistry
D055396:Bone Morphogenetic Protein 2; D005337:Fibrin