Significance of Epigenetic Landscape in Cartilage Regeneration from the Cartilage Development and Pathology Perspective

Li, Jingting; Ohliger, James; Pei, Ming

doi:10.1089/scd.2014.0002

Cited by 9 publications

(6 citation statements)

References 187 publications

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“…4) [160]. For instance, hypoxic stress often results in changes of gene expression that are affiliated with adaptations in chromatin structure by histone modifying and chromatin remodeling complexes [161,162].…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia also triggers microRNAs in the regulation of vascular endothelial growth factor (VEGF) for angiogenesis, some of which are downstream effectors of HIFs [163]; induction of HIF-1α in hypoxic preconditioned stem cells caused upregulation of miR-210 and this cytoprotective effect of hypoxic preconditioning could be negated by inhibition of HIF-1α or miR-210 [164]. This evidence indicates that hypoxic stress can cause epigenetic adaptation that, in adult stem cells, is dedicated not only to maintain cell stemness but also to drive cell differentiation [160]. Unfortunately, there are few reports to elucidate the rejuvenation effect of environmental preconditioning on adult stem cell proliferation and chondrogenic potential.…”

Section: Discussionmentioning

confidence: 99%

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Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Pei

2017

Biomaterials

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Adult stem cells are a promising cell source for cartilage regeneration. Unfortunately, due to donor age and ex vivo expansion, stem cell senescence becomes a huge hurdle for these cells to be used clinically. Increasing evidence indicates that environmental preconditioning is a powerful approach in promoting stem cells’ ability to resist a harsh environment post-engraftment, such as hypoxia and inflammation. However, few reports organize and evaluate the literature regarding the rejuvenation effect of environmental preconditioning on stem cell proliferation and chondrogenic differentiation capacity, which are important variables for stem cell based tissue regeneration. This report aims to identify several critical environmental factors such as oxygen concentration, growth factors, and extracellular matrix and to discuss their preconditioning influence on stem cells’ rejuvenation including proliferation and chondrogenic potential as well as underlying molecular mechanisms. We believe that environmental preconditioning based rejuvenation is a simpler and safer strategy to program pre-engraftment stem cells for better survival and enhanced proliferation and differentiation capacity without the undesired effects of some treatments, such as genetic manipulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Pei

2017

Biomaterials

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“…dECM expansion of hSDSCs and subsequent chondrogenic induction were accompanied by a significant change in both Wnt and MAPK signals, indicating potential mechanisms underlying dECM mediated hSDSC rejuvenation, which needs further in-depth investigation. Progress in understanding environment-oriented epigenetic regulatory mechanisms could benefit cartilage regeneration and engineering on a larger scale and provide more promising therapeutic applications [57]. For future clinical application, young and healthy donors can be selected for deposition of this ECM [16]; a decellularized process can minimize concerns about immune issues; and this dECM can be commercialized to make one-step in vitro expansion possible.…”

Section: Discussionmentioning

confidence: 99%

Delineation of in vitro chondrogenesis of human synovial stem cells following preconditioning using decellularized matrix

Zhang

Davis

et al. 2015

Acta Biomaterialia

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As a tissue-specific stem cell for chondrogenesis, synovium-derived stem cells (SDSCs) are a promising cell source for cartilage repair. However, a small biopsy can only provide a limited number of cells. Cell senescence from both in vitro expansion and donor age presents a big challenge for stem cell based cartilage regeneration. Here we found that expansion on decellularized extracellular matrix (dECM) full of three-dimensional nanostructured fibers provided SDSCs with unique surface profiles, low elasticity but large volume as well as fibroblast-like shape. dECM expanded SDSCs yielded larger pellets with intensive staining of type II collagen and sulfated glycosaminoglycans compared to those grown on plastic flasks while SDSCs grown in ECM yielded 28-day pellets with minimal matrix as evidenced by pellet size and chondrogenic marker staining, which was confirmed by both biochemical data and real-time PCR data. Our results also found lower levels of inflammatory genes in dECM expanded SDSCs that might be responsible for enhanced chondrogenic differentiation. Despite an increase in type X collagen in chondrogenically induced cells, dECM expanded cells had significantly lower potential for endochondral bone formation. Wnt and MAPK signals were actively involved in both expansion and chondrogenic induction of dECM expanded cells. Since young and healthy people can be potential donors for this matrix expansion system and decellularization can minimize immune concerns, human SDSCs expanded on this future commercially available dECM could be a potential cell source for autologous cartilage repair.

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“…Defining subpopulations of MSCs may provide a good foundation; some progress in this field has been made (Houlihan et al, 2012). As cells only differentiate when they exit the cell cycle, fine-tuned cell cycles at the initial stages of differentiation can influence cells to differentiate into homogeneous phenotypes (Li et al, 2014). Senescence and apoptosis inherently occur during both embryonic development and in vitro chondrogenic differentiation, so regulation of these two processes could potentially regulate chondrogenic differentiation.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Previously, multiple factors induced step-wise mesoderm differentiation and subsequent chondrogenesis through mimicking embryonic chondrogenesis (Oldershaw et al, 2010). The sequential addition of growth factors may be able to improve chondrogenesis based on gene expression of cell surface receptors and effectiveness of growth factors; withdrawal of the growth factors after nine days improves chondrogenesis (Handorf and Li, 2014). Apart from the addition of growth factors, inhibition of specific cell signalling pathways may also enhance chondrogenesis, such as the Smad1/5/8 signalling inhibitor dorsomorphin (Hellingman et al, 2011;Retting et al, 2009) or Wnt inhibitors [Gremlin 1, frizzled-related protein (FRP) or dickkopf (Dkk-1)] (Leijten et al, 2012).…”

Section: Future Perspectivesmentioning

confidence: 99%

Evolving concepts of chondrogenic differentiation: history, state-of-the-art and future perspectives

Tang

Fan²,

M³

et al. 2015

eCM

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As a cell source, multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs) are promising candidates for chondrogenic differentiation and subsequent cartilage regeneration. From previous literature, it is known that chondrogenic differentiation of MSCs inevitably leads to hypertrophy and subsequent endochondral ossification. In this review, we examine the history of currently established protocols of chondrogenic differentiation and elaborate on the roles of individual components of chondrogenic differentiation medium. We also summarise the effects of physical, chemical and biological factors involved, and propose potential strategies to differentiate MSCs into articular chondrocytes with homogenous mature phenotypes through spatial-temporal incorporation of cell differentiation and chondrogenesis.

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Significance of Epigenetic Landscape in Cartilage Regeneration from the Cartilage Development and Pathology Perspective

Cited by 9 publications

References 187 publications

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Delineation of in vitro chondrogenesis of human synovial stem cells following preconditioning using decellularized matrix

Evolving concepts of chondrogenic differentiation: history, state-of-the-art and future perspectives

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