Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells.
Xenogenic transplantation models have been developed to study human hematopoiesis in immunocompromised murine recipients. They still have limitations and therefore it is important to delineate all players within the bone marrow that could account for species-specific differences. Here, we evaluated the proliferative capacity, morphological and physical characteristics of human CD34(+) hematopoietic stem and progenitor cells (HSPCs) after co-culture on murine or human bone marrow-derived mesenchymal stromal cells (MSCs). After seven days, human CD34(+)CD133(-) HSPCs expanded to similar extents on both feeder layers while cellular subsets comprising primitive CD34(+)CD133(+) and CD133(+)CD34(-) phenotypes are reduced fivefold on murine MSCs. The number of migrating HSPCs was also reduced on murine cells suggesting that MSC adhesion influences cellular polarization of HSPC. We used atomic force microscopy-based single-cell force spectroscopy to quantify their adhesive interactions. We found threefold higher detachment forces of human HSPCs from murine MSCs compared to human ones. This difference is related to the N-cadherin expression level on murine MSCs since its knockdown abolished their differential adhesion properties with human HSPCs. Our observations highlight phenotypic, morphological and adhesive differences of human HSPCs when cultured on murine or human MSCs, which raise some caution in data interpretation when xenogenic transplantation models are used.
Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, 01307 Dresden, Germany.
Doreen
D
Reichert
Institute for Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden, 01069 Dresden, Germany.
Jens
J
Friedrichs
Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, 01307 Dresden, Germany.
Steffi
S
Ritter
Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, 01307 Dresden, Germany.
Theresa
T
Käubler
Institute for Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden, 01069 Dresden, Germany.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden 01307 Dresden, Germany.
Carsten
C
Werner
Medical Clinic and Polyclinic I, University Hospital Carl Gustav Carus, 01307 Dresden, Germany.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden 01307 Dresden, Germany.
Martin
M
Bornhäuser
Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, 01307 Dresden, Germany.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden 01307 Dresden, Germany.
Denis
D
Corbeil
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D018920:Coculture Techniques; D006023:Glycoproteins / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D022161:Transport Vesicles / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015820:Cadherins; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse