Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

Weber, William; Rouleau, Cecile; Yang, Min; Honma, Nakayuki; Kataoka, Satoshi; Roberts, Bruce; Teicher, Beverly A.

doi:10.3892/ijo_00000187

Cited by 77 publications

(63 citation statements)

References 36 publications

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“…On the one hand, these signaling pathways are functionally intact without the requirement of TEM-1 expression in most cells. On the other hand, TEM-1 expression seems to be required in some precursor cell types: mural cells (pericytes, which could be viewed as precursors of vascular smooth muscle cells), 12 endothelial progenitor cells, 31 mesenchymal stem cells (MSCs) 12,32 and stromal fibroblasts (with the potential to differentiate into many different cell types). 12 In the developing mouse embryo both stromal fibroblasts and perivascular cells were found to express elevated levels of TEM-1.…”

Section: Discussionmentioning

confidence: 99%

Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Tomkowicz

Rybiński²,

Sebeck³

et al. 2010

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Tomkowicz

Rybiński²,

Sebeck³

et al. 2010

Cancer Biology & Therapy

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“…This confirmed that CD248-expressing cells proliferate in vivo. Taken together, we suggest that CD248 1 stroma is required for full pLN expansion by increasing proliferation of mesenchymal cells in the medulla and capsule of pLN.It has recently been shown that CD248 is expressed on human bone marrow-derived mesenchymal stem cells (MSC) [19]. As such cells have been suggested to play a role in tissue remodelling and repair [20], we were interested to see whether CD248 played a role in regulating differentiation of mouse mesenchymal cells.…”

mentioning

confidence: 99%

“…It has recently been shown that CD248 is expressed on human bone marrow-derived mesenchymal stem cells (MSC) [19]. As such cells have been suggested to play a role in tissue remodelling and repair [20], we were interested to see whether CD248 played a role in regulating differentiation of mouse mesenchymal cells.…”

mentioning

confidence: 99%

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

et al. 2010

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CD248 is a cell surface receptor that specifically identifies fibroblasts and pericytes during development and in association with cancer and inflammation. However, its function is poorly defined and its role in lymphoid organs not studied. Here, we used (4-hydroxy-3-nitrophenyl)acetyl chicken c-globulin immunisation and mice lacking CD248 to study whether CD248 modulates popliteal LN (pLN) expansion and subsequent immune responses. We have found that CD248 is required for complete pLN expansion but not for co-ordination of B and T cell compartmentalisation or antibody production following (4-hydroxy-3-nitrophenyl)acetyl chicken c-globulin immunisation. In vitro, we show that CD248 expression in human MG63 stromal cells and mouse embryonic fibroblasts leads to a pro-proliferative and pro-migratory phenotype. This correlates with a proliferating CD248 1 population observed in vivo during pLN expansion. Taken together, these data highlight a role for CD248 in secondary lymphoid organ remodelling during adaptive immune responses.Key words: CD248 . Endosialin . Fibroblast . Lymphoid tissue . Stromal cells IntroductionDuring an immune response, secondary lymphoid organs (SLO) expand significantly. However, mechanisms that regulate this have been relatively understudied with leucocyte accumulation rather than stromal cell expansion being the focus. Logic dictates that there has to be co-ordinated expansion of tissue structure to accommodate the rapidly expanding leucocyte populations. This expansion includes not only an intricate network of fibroblasts that provide an important structural scaffold but also the formation of new blood and lymph vessels to oxygenate and allow transport of lymphocytes into and out of the organ [1].CD248/endosialin is a relatively new marker for a subset of stromal cells in developing tissues. It is a member of an emerging transmembrane protein family implicated in tissue remodelling and repair, which includes CD141 and CD93 [2,3] 1884expressed on fibroblasts and pericytes during development and in tumour-associated stroma [4][5][6][7]. An important role for CD248 within tumour stroma has been highlighted in CD248-deficient mice; abdominal tumours implanted into mice lacking CD248 demonstrated reduced growth, invasion and metastasis [8]. This, coupled with the finding that CD248 expression is regulated by hypoxia inducible factor-2a [9], suggests that CD248 may provide an important link between hypoxia and tissue remodelling allowing synchronisation of these processes.We have previously proposed a role for CD248 in development and infection-dependent activation of SLO stroma [10]. Whether CD248 is required for tissue remodelling was not explored nor was its function. Therefore, to more fully understand the requirements for CD248 during remodelling, we compared the degree of popliteal LN (pLN) expansion in WT and CD248 KO mice following immunisation with (4-hydroxy-3-nitrophenyl)acetyl chicken g-globulin (NP-CGG). The ability of CD248 to regulate cell migration and proliferation in vitro w...

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“…In contrast to the bene icial effects, however, adverse effects of MSCs on multiple tumour models have also been reported. It has been found that in tumour tissues MSCs could differentiate into myo ibroblastslike cells, which have been proven to play a crucial role in tumour promotion through multiple mechanisms, including promotion of tumour stroma remodelling and tumour invasiveness 30 . It was demonstrated that when exposed to a tumourconditioned medium over a long period MSCs gained a myo ibroblastic phenotype as evidenced by an expression of carcinoma-associated markers, including stroma-derived factor-1 (SDF-1), α-SMA and ibroblast surface protein 31 .…”

Section: Mscs Therapy In Liver Cancermentioning

confidence: 99%

Treating end-stage liver diseases with mesenchymal stem cells: An oak is not felled at one stroke

Li¹,

He²,

Xiao³

et al. 2013

OA Tissue Engineering

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IntroductionCurrently, orthotropic liver transplantation is the only effective therapy for end-stage liver diseases, including acute liver failure, cirrhosis and liver cancer. However, the shortage of donor liver severely limits its application. The advent of the technology of turning mesenchymal stem cells from adult tissues into liver cells has opened the possibility of obtaining transplantable hepatocytes without donor livers and raised much interest in the ield of hepatology. In this review, we summarized recent advances in using mesenchymal stem cells as a therapeutic strategy for treating liver diseases. ConclusionFor the acute liver failure, many studies have demonstrated promising results. However, for the treatment of cirrhosis and liver cancer, the results do vary. Therefore, further studies are warranted before considering mesenchymal stem cells for active use in clinical applications.

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Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

Cited by 77 publications

References 36 publications

Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

Treating end-stage liver diseases with mesenchymal stem cells: An oak is not felled at one stroke

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