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Engineering spatial control of multiple differentiation fates within a stem cell population

Ker, EDF and Chu, B and Phillippi, JA and Gharaibeh, B and Huard, J and Weiss, LE and Campbell, PG (2011) Engineering spatial control of multiple differentiation fates within a stem cell population. Biomaterials, 32 (13). 3413 - 3422. ISSN 0142-9612

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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 toward 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. © 2011 Elsevier Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Ker, EDF
Chu, B
Phillippi, JAjap103@pitt.eduJAP103
Gharaibeh, Bburhan@pitt.eduBURHAN0000-0002-5947-1232
Huard, J
Weiss, LE
Campbell, PG
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 May 2011
Date Type: Publication
Journal or Publication Title: Biomaterials
Volume: 32
Number: 13
Page Range: 3413 - 3422
DOI or Unique Handle: 10.1016/j.biomaterials.2011.01.036
Schools and Programs: School of Medicine > Cardiothoracic Surgery
School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 0142-9612
MeSH Headings: Animals; Cell Differentiation--drug effects; Cell Line; Cells, Cultured; Fibroblast Growth Factor 2--pharmacology; Fluorescent Antibody Technique; Humans; Intercellular Signaling Peptides and Proteins--pharmacology; Mesenchymal Stromal Cells--cytology; Mesenchymal Stromal Cells--drug effects; Mice; Myoblasts--cytology; Myoblasts--drug effects; Osteoblasts--cytology; Osteoblasts--drug effects; Polymerase Chain Reaction; Stem Cells--cytology; Stem Cells--drug effects; Tendons--cytology
Other ID: NLM NIHMS267076, NLM PMC3060662
PubMed Central ID: PMC3060662
PubMed ID: 21316755
Date Deposited: 04 Apr 2014 15:56
Last Modified: 02 Feb 2019 16:58


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