Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture

Wang, Yuchuan; Huso, David; Harrington, Jr. Joseph E.; Kellner, Joshua; Jeong, Dong Kee; Turney, Jennifer; McNiece, Ian

doi:10.1080/14653240500363216

Cited by 244 publications

(180 citation statements)

References 21 publications

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“…For example, a subpopulation of cells in human MSC culture was noted to appear morphologically distinct from typical MSCs [122]. These cells showed a high level of telomerase activity compared with typical MSCs and formed tumours with aggressive growth when transplanted into NOD/SCID mice.…”

Section: Expansion Of Cell Number and In Vitro Culturementioning

confidence: 99%

Tissue engineering and the intervertebral disc: the challenges

2008

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Disc degeneration is a common disorder. Although the back pain that can develop in association with this is rarely life-threatening, the annual cost in terms of morbidity, lost productivity, medical expenses and workers' compensation benefits is significant. Surgical intervention as practised currently is directed towards removing the damaged or altered tissue. Development of new treatment modalities is critical as there is a growing consensus that the strategies used currently for symptomatic degenerative disc disease may not be effective. Accordingly, there is a need to develop an entirely new way to treat this disorder; regenerative medicine and tissue engineering approaches appear particularly promising in this regard. This paper reviews some of the challenges that currently are limiting the clinical application of this approach to the treatment of disc degeneration.

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Section: Expansion Of Cell Number and In Vitro Culturementioning

confidence: 99%

Tissue engineering and the intervertebral disc: the challenges

2008

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“…Consequently, the possibility that hMSCs may also undergo spontaneous transformation after long-term in vitro culture became a concern, which has drawn especial attention in recent years. One group described the outgrowth of a cell population with a transformed phenotype derived from normal BM-hMSC cultures, although the authors could not rule out the presence of a rare CD133 + non-stromal cell population in the starting material [20] (Table 1). Likewise, it is worth mentioning that two other comprehensive studies initially reporting spontaneous transformation of both BM-hMSCs and human adiposederived mesenchymal stem cells (hASCs) after longterm in vitro culture have been recently retracted due to cross-contamination of the MSC cultures with cancer cell lines [21,22].…”

Section: Spontaneous Transformation Of Mscsmentioning

confidence: 99%

Modeling sarcomagenesis using multipotent mesenchymal stem cells

2011

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Because of their unique properties, multipotent mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells being used worldwide in a wide array of clinical applications. Overall, compelling evidence supports the long-term safety of ex vivo expanded human MSCs, which do not seem to transform spontaneously. However, experimental data reveal a link between MSCs and cancer, and MSCs have been reported to inhibit or promote tumor growth depending on yet undefined conditions. Interestingly, solid evidence based on transgenic mice and genetic intervention of MSCs has placed these cells as the most likely cell of origin for certain sarcomas. This research area is being increasingly explored to develop accurate MSC-based models of sarcomagenesis, which will be undoubtedly valuable in providing a better understanding about the etiology and pathogenesis of mesenchymal cancer, eventually leading to the development of more specific therapies directed against the sarcoma-initiating cell. Unfortunately, still little is known about the mechanisms underlying MSC transformation and further studies are required to develop bona fide sarcoma models based on human MSCs. Here, we comprehensively review the existing MSC-based models of sarcoma and discuss the most common mechanisms leading to tumoral transformation of MSCs and sarcomagenesis.

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“…While teratoma formation is a defining criterion for ES cells, and as little as 2 ES cells contaminating a graft of mature cells have been shown to give rise to teratomas (Hentze et al, 2007), adult and BMDCs do not form tumors on a regular basis. However, in vitro and mouse studies have shown that MSCs can undergo transformation or support growth of existing tumors (Djouad et al, 2003;Houghton et al, 2004;Wang et al, 2005;Tolar et al, 2007). So far, there have been no reports of transformation of administered BMDCs into tumors in patients treated with autologous or allogeneic stem cells, but experience is limited and follow-up times are insufficient to allow assessment of true long-term effects.…”

Section: Side Effects and Dangersmentioning

confidence: 99%