Human Migratory Meniscus Progenitor Cells Are Controlled via the TGF-β Pathway

Muhammad, Hayat; Schminke, Boris; Bode, Christa; Roth, Moritz; Albert, Julius; Heyde, Silvia von der; Rosen, Vicki; Miosge, Nicolai

doi:10.1016/j.stemcr.2014.08.010

Cited by 65 publications

(73 citation statements)

References 42 publications

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“…Identification of CD166-positive cells in the surface layers of the meniscus in our current study is consistent with previous reports indicating the presence of stem or progenitor cells in this area (23–25). The expression of CD166 suggests that these cells could be progenitors.…”

Section: Discussionsupporting

confidence: 93%

“…The presence of progenitor cells would appear to be in conflict with the capacity of the avascular region to self-heal (14–16). Meniscus progenitors in normal meniscal tissue are likely quiescent, but cells positive for several stem cell markers including CD105, CD106 and STRO-1 emerge from and migrate into diseased or disrupted tissues (25). Although the inner bulk tissue of the avascular region lacked identifiable progenitor populations, the presence of progenitors on the surface of the meniscus opens the possibility of developing methods to better characterize, stimulate, and utilize these cells.…”

Section: Discussionmentioning

confidence: 99%

“…At the very surface (superficial zone of meniscus), is a cell type without cell extensions and apparently analogous to the superficial zone (SZ) of articular cartilage. Like the superficial zone of cartilage, the superficial zone of the meniscus may harbor progenitor cells (23–25). Ghadially et al indicated similarity between the cells of the meniscal superficial zone to those of chondrocytes in the SZ of articular cartilage and the cells of the inner regions of the meniscus to the chondrocytes of the middle and deep zones of articular cartilage (26).…”

Section: Introductionmentioning

confidence: 99%

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Relevance of meniscal cell regional phenotype to tissue engineering

Grogan

Pauli

Lotz

et al. 2017

Connective Tissue Research

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Purpose Meniscus contains heterogeneous populations of cells that have not been fully characterized. Cell phenotype is often lost during culture; however, culture expansion is typically required for tissue engineering. We examined and compared cell surface molecule expression levels on human meniscus cells from the vascular and avascular regions and articular chondrocytes while documenting changes during culture-induced dedifferentiation. Materials and Methods Expression of 16 different surface molecules were examined by flow cytometry after monolayer culture for 24 h, 1 week, and 2 weeks. Menisci were also immunostained to document the spatial distributions of selected surface molecules. Results Meniscus cells and chondrocytes exhibited several similarities in surface molecule profiles with dynamic changes during culture. A greater percentage of meniscal cells were positive for CD14, CD26, CD49c, and CD49f compared to articular chondrocytes. Initially, more meniscal cells from the vascular region were positive for CD90 compared to cells from the avascular region or chondrocytes. Cells from the vascular region also expressed higher levels of CD166 and CD271 compared to cells from the avascular region. CD90, CD166, and CD271-positive cells were predominately perivascular in location. However, CD166-positive cells were also located in the superficial layer and in the adjacent synovial and adipose tissue. Conclusions These surface marker profiles provide a target phenotype for differentiation of progenitors in tissue engineering. The spatial location of progenitor cells in meniscus is consistent with higher regenerative capacity of the vascular region, while the surface progenitor subpopulations have potential to be utilized in tears created in the avascular region.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relevance of meniscal cell regional phenotype to tissue engineering

Grogan

Pauli

Lotz

et al. 2017

Connective Tissue Research

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“…Vanderploeg et al [6] showed collagen type VI to be concentrated in inner meniscal regions and localized to the pericellular matrix; in this study, omECM supplementation downregulated Col6 expression, as compared with Controls and imECM constructs. In examining additional putative meniscal cell markers [31], ECM supplementation tended to have a negligible or inhibitory effect at early time points, with broad equivalency across groups by day 42. The extent that these transcriptional changes are meaningful for tissue engineering application remains uncertain, given the paucity of studies characterizing the phenotypes of cells across various meniscus regions.…”

Section: Discussionmentioning

confidence: 99%

Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix

et al. 2017

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Extracellular matrix (ECM) derived from decellularized tissues has been found to promote tissue neogenesis, most likely mediated by specific biochemical and physical signaling motifs that promote tissue-specific differentiation of progenitor cells. Decellularized ECM has been suggested to be efficacious for the repair of tissue injuries. However, decellularized meniscus contains a dense collagenous structure, which impedes cell seeding and infiltration and is not readily applicable for meniscus repair. In addition, the meniscus consists of two distinct anatomical regions that differ in vascularity and cellular phenotype. The purpose of this study was to explore the region-specific bioactivity of solubilized ECM derived from the inner and outer meniscal regions as determined in 2D and 3D cultures of adult mesenchymal stem cells (MSCs). When added as a medium supplement to 2D cultures of MSCs, urea-extracted fractions of the inner (imECM) and outer meniscal ECM (omECM) enhanced cell proliferation while imECM most strongly upregulated fibrochondrogenic differentiation on the basis of gene expression profiles. When added to 3D cultures of MSCs seeded in photocrosslinked methacrylated gelatin (GelMA) hydrogels, both ECM fractions upregulated chondrogenic differentiation as determined by gene expression and protein analyses, as well as elevated sulfated glycosaminoglycan sGAG content, compared to ECM-free controls. The chondrogenic effect at day 21 was most pronounced with imECM supplementation, but equivalent between ECM groups by day 42. Despite increased cartilage matrix, imECM and omECM constructs possessed compressive moduli similar to controls. In conclusion, soluble meniscal ECM may be considered for use as a tissue-specific reagent to enhance chondrogenesis for MSC-based 3D cartilage tissue engineering.

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“…The existence of these progenitor cells was first proposed by Hayes et al on the basis of their observation that cartilage exhibits appositional growth during development. 20 Mesenchymal progenitor cells have been found in many areas of the joint, including cartilage, synovial lining, bone marrow, infrapatellar fat pad, meniscus, and even tendons, [21][22][23][24][25][26][27][28][29] and it has been proposed that they may be quiescent remnant cells from the developing limb bud mesenchyme. 30 Cartilage-derived mesenchymal progenitors make up a small percentage of all cells in the cartilage tissue 31 and reside side-by-side with the more abundant chondrocytes throughout cartilage; however, they are most abundantly found in the superficial zone, specifically in the articular surface.…”

Section: Local Stem/progenitor Cellsmentioning

confidence: 99%

The influence of tissue microenvironment on stem cell–based cartilage repair

Jayasuriya

Chen

Liu

et al. 2016

Annals of the New York Academy of Sciences

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Mesenchymal stem/progenitor cells and induced pluripotent stem cells have become viable cell sources for prospective cell-based cartilage engineering and tissue repair. The development and function of stem cells are influenced by the tissue microenvironment. Specifically, the local tissue microenvironment can dictate how stem cells integrate into the existing tissue matrix and how successfully they can restore function to the damaged area in question. This review focuses on the microenvironmental features of articular cartilage and how they influence stem cell–based cartilage tissue repair. Also discussed are current tissue-engineering strategies used in combination with cell-based therapies, all of which are designed to mimic the natural properties of cartilage tissue in order to achieve a better healing response.

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Human Migratory Meniscus Progenitor Cells Are Controlled via the TGF-β Pathway

Cited by 65 publications

References 42 publications

Relevance of meniscal cell regional phenotype to tissue engineering

Relevance of meniscal cell regional phenotype to tissue engineering

Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix

The influence of tissue microenvironment on stem cell–based cartilage repair

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