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Mesenchymal stem cell stimulation of tissue growth depends on differentiation state.

ABSTRACT: The osteochondral microenvironment involves a complex milieu of cues that facilitate proper tissue development, homeostasis, and repair. This environment is disrupted in disease states such as osteoarthritis. Mesenchymal stem cells (MSCs) are under clinical investigation for the treatment of osteoarthritis given their capacity to differentiate into chondrocytes as well as to secrete a wide array of biologically active factors that support cell proliferation and tissue formation. In fact, the therapeutic action of these cells in many clinical applications is now thought to be at least partially dependent on their secretory capacity. Previous work demonstrated that MSCs were capable of stimulating chondrocyte growth and tissue production, whereas tissue-derived osteoblasts were not stimulatory. This study investigated the stimulatory capacity of MSCs during osteogenesis and the impact of MSC phenotype on cartilage stimulation. Cell interactions were examined in 3 coculture systems to confirm that trends were not dependent on material: traditional cell culture insert coculture, bilayered poly(ethylene glycol) gels, and a scaffold comprised of a layer of poly(ethylene glycol) polymerized onto a poly(lactic-co-glycolic) acid-based scaffold. Results demonstrated that MSCs predifferentiated toward an osteogenic phenotype for 3 days exhibited enhanced stimulation of chondrocyte extracellular matrix production, whereas longer periods of predifferentiation decreased the magnitude of observed stimulation. Further, tissue formation by the MSCs themselves showed greater dependence on the coculture system than the presence of other cells or length of predifferentiation.

SUBMITTER: Rothenberg AR

PROVIDER: S-EPMC3128769 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Mesenchymal stem cell stimulation of tissue growth depends on differentiation state.

Rothenberg Ashley R AR Ouyang Lee L Elisseeff Jennifer H JH

Stem cells and development 20101103 3

The osteochondral microenvironment involves a complex milieu of cues that facilitate proper tissue development, homeostasis, and repair. This environment is disrupted in disease states such as osteoarthritis. Mesenchymal stem cells (MSCs) are under clinical investigation for the treatment of osteoarthritis given their capacity to differentiate into chondrocytes as well as to secrete a wide array of biologically active factors that support cell proliferation and tissue formation. In fact, the the ...[more]

PMID: 20887213

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Project description:Cell-based therapy has become a resource for the treatment of cardiovascular diseases; however, there are some conundrums to achieve. In vitro cardiomyocyte generation could be a solution for scaling options in clinical applications. Variability on cardiac differentiation in previously reported studies from adipose tissue-derived mesenchymal stem cells (ASCs) and the lack of measuring of the cardiomyocyte differentiation efficiency motivate the present study. Here, we improved the ASC-derived cardiomyocyte-like cell differentiation efficiency with a directed cardiomyocyte differentiation protocol: BMP-4 + VEGF (days 0-4) followed by a methylcellulose-based medium with cytokines (IL-6 and IL-3) (days 5-21). Cultures treated with the directed cardiomyocyte differentiation protocol showed cardiac-like cells and "rosette-like structures" from day 7. The percentage of cardiac troponin T- (cTnT-) positive cells was evaluated by flow cytometry to assess the cardiomyocyte differentiation efficiency in a quantitative manner. ASCs treated with the directed cardiomyocyte differentiation protocol obtained a differentiation efficiency of up to 44.03% (39.96%±3.78) at day 15 without any enrichment step. Also, at day 21 we observed by immunofluorescence the positive expression of early, late, and cardiac maturation differentiation markers (Gata-4, cTnT, cardiac myosin heavy chain (MyH), and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCa2)) in cultures treated with the directed cardiomyocyte differentiation protocol. Unlike other protocols, the use of critical factors of embryonic cardiomyogenesis coupled with a methylcellulose-based medium containing previously reported cardiogenic cytokines (IL-6 and IL-3) seems to be favorable for in vitro cardiomyocyte generation. This novel efficient culture protocol makes ASC-derived cardiac differentiation more efficient. Further investigation is needed to identify an ASC-derived cardiomyocyte surface marker for cardiac enrichment.

Dataset Information

Mesenchymal stem cell stimulation of tissue growth depends on differentiation state.

Publications

Mesenchymal stem cell stimulation of tissue growth depends on differentiation state.

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