A new technique to expand human mesenchymal stem cells using basement membrane extracellular matrix

Matsubara, Takehiro; Tsutsumi, S.; Pan, Hong; Hiraoka, Hisatada; Oda, Ryo; Nishimura, Masahiro; Kawaguchi, Hiroshi; Nakamura, Kimie; Kato, Yukio

doi:10.1016/j.bbrc.2003.11.143

Cited by 91 publications

(68 citation statements)

References 17 publications

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“…Thus, an important challenge in immunotherapy is to improve the replicative capacity of MSCs. In the past 10 years, several methods have been developed for MSC isolation/expansion in vitro, such as using flow cytometry or mononuclear cell gravity sedimentation for isolation (32,33), and using magnetic nanoparticles or basement membrane extracellular matrix, together with culture medium supplementation with different growth factors for expansion (34,35). Although …”

Section: A B Discussionmentioning

confidence: 99%

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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Abstract. Improved knowledge of the immunological properties of mesenchymal stem cells (MSCs) creates a potential cell-mediated immunotherapeutic approach for arthritic diseases. The low frequency of MSCs necessitates their in vitro expansion prior to clinical use. As sequential passage has been used as the most popular strategy for expansion of MSCs, the effect of long-term culture on the immunological properties of MSCs is not clear. In this study, we observed that the morphology of MSCs showed the typical characteristics of the Hayflick model of cellular aging during sequential expansion. The growth kinetics of MSCs decreased while the number of MSCs staining positive for SA β-gal (senescence marker) increased in long-term culture. Although long-term culture exerts less of an effect on the immunophenotype of MSCs, the immunosuppressive effects of MSCs on the allogeneic T-cell proliferation, activation-antigen expression (CD69 and CD25) and cytokine production (IFN-γ, TNF-α, IL-10) were significantly impaired following stimulation with phytohemagglutinin (PHA).

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Section: A B Discussionmentioning

confidence: 99%

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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“…Moreover, the expression of laminins exists in developing and normal cartilage but disappears in degenerative, traumatically-damaged cartilage and in cartilage that fails clinical repair, suggesting a spatiotemporal distribution and function of laminins in chondrogenesis (Foldager et al, 2004;Foldager et al, 2016). Growing evidence shows that ECM components can induce chondrogenic differentiation in chick embryo limb-bud mesenchymal cells and human MSCs, but laminin alone fails to drive chondrogenic activity (Bradham et al, 1995;Matsubara et al, 2004), suggesting that laminins might participate in the process of chondrogenesis with other regulatory factors. For instance, LM-332 promotes proliferation but suppresses chondrogenic differentiation (Lindner et al, 2010) by regulating integrin α3β1 activities in human MSCs and mouse ATDC5 cells (Hashimoto et al, 2005;Hashimoto et al, 2006), while favorably enhancing osteogenesis via an integrin/FAK/ERK1/2 signaling pathway (Salasznyk et al, 2007).…”

Section: Negative Effectsmentioning

confidence: 99%

The role of laminins in cartilaginous tissues: from development to regeneration

Sun¹,

Wang²,

Toh³

et al. 2017

eCM

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As a key molecule of extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells' proliferation and chondrogenic differentiation. With this information, we hope to facilitate an understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

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“…The extracellular matrix is a powerful regulator of stem cell function (11,12). Cell-matrix interactions are mediated, to a large extent, by the integrin family of transmembrane receptors (13).…”

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confidence: 99%

α2β1 Integrin Regulates Lineage Commitment in Multipotent Human Colorectal Cancer Cells*

Kirkland

Ying

2008

Journal of Biological Chemistry

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The human colorectal epithelium is maintained by multipotent stem cells that give rise to absorptive, mucous, and endocrine lineages. Recent evidence suggests that human colorectal cancers are likewise maintained by a minority population of socalled cancer stem cells. We have previously established a human colorectal cancer cell line with multipotent characteristics (HRA-19) and developed a serum-free medium that induces endocrine, mucous and absorptive lineage commitment by HRA-19 cells in vitro. In this study, we investigate the role of the ␤1 integrin family of cell surface extracellular matrix receptors in multilineage differentiation by these multipotent human colorectal cancer cells. We show that endocrine and mucous lineage commitment is blocked in the presence of functionblocking antibodies to ␤1 integrin. Function-blocking antibodies to ␣2 integrin also blocked both HRA-19 endocrine lineage commitment and enterocytic differentiation by Caco-2 human colon cancer cells; both effects being abrogated by the MEK inhibitor, PD98059, suggesting a role for ERK signaling in ␣2-mediated regulation of colorectal cancer cell differentiation. To further explore the role of ␣2 integrin in multilineage differentiation, we established multipotent cells expressing high levels of wild-type ␣2 integrin or a non-signaling chimeric ␣2 integrin. Overexpression of wild-type ␣2 integrin in HRA-19 cells significantly enhanced endocrine and mucous lineage commitment, while cells expressing the non-signaling chimeric ␣2 integrin had negligible ability for either endocrine or mucous lineage commitment. This study indicates that the collagen receptor ␣2␤1 integrin is a regulator of cell fate in human multipotent colorectal cancer cells.A small population of multipotent epithelial stem cells maintains the integrity and function of the adult intestinal epithelium (1) Colorectal epithelial stem cells proliferate slowly giving rise to daughter cells that undergo a phase of rapid proliferation and then differentiate into absorptive, mucous, and endocrine cells. Homeostasis requires a precise balance between stem cell renewal and generation of lineage-committed cells; processes regulated by the Wnt, TGF-␤, Hedgehog, and Notch pathways (2). Dysregulation of the Wnt signaling pathway, a critical regulator of normal stem cell renewal, is commonly present in colorectal cancer as the result of well described mutations in Wnt signaling components(3). This suggests that signaling cascades that promote normal colorectal epithelial stem cell renewal persist in colorectal cancer cells. Indeed there is growing support for the idea that human cancers, including colorectal cancer, are diseases of stem cells (4, 5). It has been shown that only a small minority of tumor cells, termed cancer stem cells, are able to initiate tumor growth. Furthermore, putative human colorectal cancer stem cells have been isolated on the basis of their expression of epithelial cell adhesion molecule and CD44 (6) or CD133 (7,8). However the relationship between cancer stem...

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A new technique to expand human mesenchymal stem cells using basement membrane extracellular matrix

Cited by 91 publications

References 17 publications

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

The role of laminins in cartilaginous tissues: from development to regeneration

α2β1 Integrin Regulates Lineage Commitment in Multipotent Human Colorectal Cancer Cells*

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