Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche.
The perivascular niche is a complex microenvironment containing mesenchymal stem cells (MSCs), among other perivascular cells, as well as temporally organized biochemical and biophysical gradients. Due to a lack of conclusive phenotypic markers, MSCs' identity, heterogeneity and function within their native niche remain poorly understood. The in vitro reconstruction of an artificial three-dimensional (3D) perivascular niche would offer a powerful alternative to study MSC behavior under more defined conditions. To this end, we here present a poly(ethylene glycol)-based in vitro model that begins to mimic the spatiotemporally controlled presentation of biological cues within the in vivo perivascular niche, namely a stably localized platelet-derived growth factor B (PDGF-BB) gradient. We show that 3D-encapsulated MSCs respond to soluble PDGF-BB by proliferation, spreading, and migration in a dose-dependent manner. In contrast, the exposure of MSCs to 3D matrix-tethered PDGF-BB gradients resulted in locally restricted morphogenetic responses, much as would be expected in a native perivascular niche. Thus, the herein presented artificial perivascular niche model provides an important first step towards modeling the role of MSCs during tissue homeostasis and regeneration.
Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Schmelzbergstr. 12, 8091 Zurich, Switzerland. martin.ehrbar@usz.ch.
P S
PS
Lienemann
Y R
YR
Devaud
R
R
Reuten
B R
BR
Simona
M
M
Karlsson
W
W
Weber
M
M
Koch
M P
MP
Lutolf
V
V
Milleret
M
M
Ehrbar
D000328:Adult; D000077214:Becaplermin; D001808:Blood Vessels / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage*; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin