Engineering spatial control of multiple differentiation fates within a stem cell population.
Engineering spatial control of multiple differentiation fates within a stem cell population.
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DOI：
10.1016/j.biomaterials.2011.01.036
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发表时间：
2011-05
期刊：
影响因子：
14
通讯作者：
Campbell, Phil G.
中科院分区：
文献类型：
--
作者：
Ker, Elmer D. F.;Chu, Bur;Phillippi, Julie A.;Gharaibeh, Burhan;Huard, Johnny;Weiss, Lee E.;Campbell, Phil G.
关键词：
The capability to engineer microenvironmental cues to direct a stem cell population toward multiple fates, simultaneously, in spatially defined regions is important for understanding the maintenance and repair of multi-tissue units. We have previously developed an inkjet-based bioprinter to create patterns of solid-phase growth factors (GFs) immobilized to an extracellular matrix (ECM) substrate, and applied this approach to drive muscle-derived stem cells toward osteoblasts ‘on–pattern’ and myocytes ‘off–pattern’ simultaneously. Here this technology is extended to spatially control osteoblast, tenocyte and myocyte differentiation simultaneously. Utilizing immunofluorescence staining to identify tendon-promoting GFs, fibroblast growth factor-2 (FGF-2) was shown to upregulate the tendon marker Scleraxis (Scx) in C3H10T1/2 mesenchymal fibroblasts, C2C12 myoblasts and primary muscle-derived stem cells, while downregulating the myofibroblast marker α-smooth muscle actin (α-SMA). Quantitative PCR studies indicated that FGF-2 may direct stem cells towards a tendon fate via the Ets family members of transcription factors such as pea3 and erm. Neighboring patterns of FGF-2 and bone morphogenetic protein-2 (BMP-2) printed onto a single fibrin-coated coverslip upregulated Scx and the osteoblast marker ALP, respectively, while non-printed regions showed spontaneous myotube differentiation. This work illustrates spatial control of multi-phenotype differentiation and may have potential in the regeneration of multi-tissue units.
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