Mesenchymal stem cells

Short, Brenton; Brouard, Nathalie; Occhiodoro-Scott, Teresa; Ramakrishnan, Anand; Simmons, Paul J.

doi:10.1016/j.arcmed.2003.09.007

Cited by 255 publications

(183 citation statements)

References 61 publications

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“…It could be hypothesized that control EL-MSCs are in a relatively early stage of differentiation toward an endothelial lineage (30,31), given the lack of expression of CD31, features of mature endothelial cells, and lack of CD105-specific and CD166-specific markers of MSCs (32). Our preliminary results concerning the expression of vWF might confirm that this molecule can be expressed by MSCs after specific proendothelial 2002 CIPRIANI ET AL stimuli, although the reason for the differences observed among SSc patients is not clear.…”

Section: Discussionmentioning

confidence: 99%

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Cipriani

Guiducci

Miniati

et al. 2007

Arthritis & Rheumatism

146

102

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Objective. Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair.Methods. MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit-fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed.Results. MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2؉, CXCR4؉, VEGFR-2؉/CXCR4؉ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell-derived factor 1 to cultured SSc ELMSCs increased their angiogenic potential less than that in controls.Conclusion. Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.

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Section: Discussionmentioning

confidence: 99%

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Cipriani

Guiducci

Miniati

et al. 2007

Arthritis & Rheumatism

146

102

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“…Each colony is derived from a single cell called a colony-forming unit fibroblast (CFU-F). MSCs are rare, declining in frequency with age, being present in bone marrow aspirates at a frequency of 0.1-5/10 5 cells in rodents and 1-20/10 5 in humans [82]. To the properties of plastic adherence and trilineage potential, a working party has suggested that human MSCs be further defined as expressing CD105, CD73 and CD90, but lacking expression of CD45, CD34, CD14 or CD11b, CD79α or CD19 and HLA-DR surface markers [83].…”

Section: Bone Marrowmentioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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“…(21)(22)(23) In addition, new evidence suggests that the majority of MSCs are not actually located within the bone marrow but rather within the bone tissue itself or, more specifically, within the vascular system of the bone. (24)(25)(26) Therefore, employing fluorescence-activated cell sorting (FACS) for Sca-1 on cells purified from murine bone tissue following a rigorous depletion of hematopoietic cells results in two populations enriched for mesenchymal progenitor cells: highly proliferative Sca-1 þ MSCs, which have been shown to exhibit adipogenic, chondrogenic, and osteogenic potential, and Sca-1 À CD51 þ cells that are more committed toward the osteogenic lineage and hence referred to as osteoprogenitor cells. (6,25,27) The regulation of MSCs within the bone microenvironment is complex, involving numerous systemic and local factors.…”

Section: Introductionmentioning

confidence: 99%

“…(24)(25)(26) Therefore, employing fluorescence-activated cell sorting (FACS) for Sca-1 on cells purified from murine bone tissue following a rigorous depletion of hematopoietic cells results in two populations enriched for mesenchymal progenitor cells: highly proliferative Sca-1 þ MSCs, which have been shown to exhibit adipogenic, chondrogenic, and osteogenic potential, and Sca-1 À CD51 þ cells that are more committed toward the osteogenic lineage and hence referred to as osteoprogenitor cells. (6,25,27) The regulation of MSCs within the bone microenvironment is complex, involving numerous systemic and local factors. Therefore, the use of purified populations of mesenchymal progenitor cells from bone tissue avoids the complicating influence of multiple cell types present in the heterogeneous BMSC cultures.…”

Section: Introductionmentioning

confidence: 99%

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

Lee

Doyle

Sainsbury

et al. 2010

Journal of Bone and Mineral Research

101

135

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The neuropeptide Y (NPY) system has been implicated in the regulation of bone homeostasis and osteoblast activity, but the mechanism behind this is unclear. Here we show that Y1 receptor signaling is directly involved in the differentiation of mesenchymal progenitor cells isolated from bone tissue, as well as the activity of mature osteoblasts. Importantly, the mRNA levels of two key osteogenic transcription factors, runx2 and osterix, as well as the adipogenic transcription factor PPAR-g, were increased in long bones of Y1 À/À mice compared with wild-type mice. In vitro, bone marrow stromal cells (BMSCs) isolated from Y1 À/À mice formed a greater number of mineralized nodules under osteogenic conditions and a greater number of adipocytes under adipogenic conditions than controls. In addition, both the number and size of fibroblast colony-forming units formed in vitro by purified osteoprogenitor cells were increased in the absence of the Y1 receptors, suggestive of enhanced proliferation and osteogenesis. Furthermore, the ability of two specific populations of mesenchymal progenitor cells isolated from bone tissue, an immature mesenchymal stem cell population and a more committed osteoprogenitor cell population, to differentiate into osteoblasts and adipocytes in vitro was enhanced in the absence of Y1 receptor signaling. Finally, Y1 receptor deletion also enhanced the mineral-producing ability of mature osteoblasts, as shown by increased in vitro mineralization by BMSCs isolated from osteoblast-specific Y1 À/À mice. Together these data demonstrate that the NPY system, via the Y1 receptor, directly inhibits the differentiation of mesenchymal progenitor cells as well as the activity of mature osteoblasts, constituting a likely mechanism for the high-bone-mass phenotype evident in Y1 À/À mice. ß

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Mesenchymal stem cells

Cited by 255 publications

References 61 publications

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Attributes of adult stem cells

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

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