Cell cycle and tissue of origin contribute to the migratory behaviour of human fetal and adult mesenchymal stromal cells.
Mesenchymal stromal cells (MSC) are potential cells for cellular therapies, in which the recruitment and migration of MSC towards injured tissue is crucial. Our data show that culture-expanded MSC from fetal lung and bone marrow, adult bone marrow and adipose tissue contained a small percentage of migrating cells in vitro, but the optimal stimulus was different. Overall, fetal lung-MSC had the highest migratory capacity. As fetal bone marrow-MSC had lower migratory potential than fetal lung-MSC, the tissue of origin may determine the migratory capacity of MSC. No additive effect in migration towards combined stimuli was observed, which suggests only one migratory MSC fraction. Interestingly, actin rearrangement and increased paxillin phosphorylation were observed in most MSC upon stromal cell-derived factor-1alpha or platelet-derived growth factor-BB stimulation, indicating that this mechanism involved in responding to migratory cues is not restricted to migratory MSC. Migratory MSC maintained differentiation and migration potential, and contained significantly less cells in S- and G2/M-phase than their non-migrating counterpart. In conclusion, our results suggest that MSC from various sources have different migratory capacities, depending on the tissue of origin. Similar to haematopoietic stem cells, cell cycle contributes to MSC migration, which offers perspectives for modulation of MSC to enhance efficacy of future cellular therapies.
Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam.
Marijke W
MW
Maijenburg
Willy A
WA
Noort
Marion
M
Kleijer
Charlotte J A
CJ
Kompier
Kees
K
Weijer
Jaap D
JD
van Buul
C Ellen
CE
van der Schoot
Carlijn
C
Voermans
D000199:Actins / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D001853:Bone Marrow / Q000196:embryology; D001854:Bone Marrow Cells / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D005333:Fetus / Q000166:cytology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology
D000199:Actins; D016023:Integrins; D051419:Paxillin