Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Lepperdinger, Günter; Brunauer, Regina; Jamnig, Angelika; Laschober, Gerhard; Kassem, Moustapha

doi:10.1016/j.exger.2008.07.004

Cited by 112 publications

(74 citation statements)

References 76 publications

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“…The former paradigm for the benefit of BMC administration focused on cell replacement; however, this concept encompassed the concerns related to cell tumorigenic potential and allogeneic transplantation (59,60). We believed that the delivery of a cell-free preparation would alleviate concerns related to tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

Ionescu

Alphonse

Arizmendi

et al. 2012

Am J Respir Cell Mol Biol

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Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T H 2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.

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Section: Discussionmentioning

confidence: 99%

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

Ionescu

Alphonse

Arizmendi

et al. 2012

Am J Respir Cell Mol Biol

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“…24 The benefits of delivering stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells, which can differentiate to give rise to CMs, 10 have been investigated. Limited success has, however, been realized using stem cells, and concerns remain regarding the potential cancer risk 25,26 and adverse immune response 25 associated with their use. Recent research has also shown the potential benefit of delivering fibroblasts to the infarct region.…”

Section: Introductionmentioning

confidence: 99%

Calcium-Alginate Hydrogel-Encapsulated Fibroblasts Provide Sustained Release of Vascular Endothelial Growth Factor

Hunt

Shelton

Henderson

et al. 2013

Tissue Engineering Part A

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“…[2][3][4] Several recent reports, however, raised the concern that hMSCs expanded in culture may emerge from senescence and generate cells that are both immortal in culture and tumorigenic in patients. 3,[5][6][7][8][9][10][11] We speculated that culture methodology could play a significant role in the putative tumorigenicity of expanded hMSC cultures. In particular, exposure to high density can substantially and irreversibly alter the characteristics of hMSCs 12,13 much as high-density cultures predispose mouse fibroblasts to spontaneous transformation.…”

mentioning

confidence: 99%

Sox11Is Expressed in Early Progenitor Human Multipotent Stromal Cells and Decreases with Extensive Expansion of the Cells

Larson

Ylöstalo

Lee

et al. 2010

Tissue Engineering Part A

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There has been considerable interest in developing new therapies with adult multipotent progenitor stromal cells or mesenchymal stem cells (MSCs) in organ replacement and repair. To be effectively seeded into scaffolds for therapy, large numbers of cells are needed, but concerns remain regarding their chromatin stability in long-term culture. We therefore expanded four donors of human MSCs (hMSCs) from bone marrow aspirates with a protocol that maintains the cells at low density. MSCs initially proliferated at average doubling times of 24 h and then gradually reached senescence after 8-15 passages (33-55 population doublings) without evidence of immortalization. Comparative genomic hybridization assays of two preparations revealed no abnormalities through 33 population doublings. One preparation had a small amplification of unknown significance in chromosome 7 (7q21:11) after 55 population doublings. Microarray assays demonstrated progressive changes in the transcriptome of the cells. However, the transcriptomes clustered more closely over time within a single passage, rather than with passage number, indicating a partial reversibility of the patterns of gene expression. One of the largest changes was a decrease in mRNA for Sox11, a transcription factor previously identified in neural progenitor cells. Knockdown of Sox11 with siRNA decreased the proliferation and osteogenic differentiation potential of hMSCs. The results suggested that assays for Sox11 may provide a biomarker for early progenitor hMSCs.

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Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Cited by 112 publications

References 76 publications

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

Calcium-Alginate Hydrogel-Encapsulated Fibroblasts Provide Sustained Release of Vascular Endothelial Growth Factor

Sox11Is Expressed in Early Progenitor Human Multipotent Stromal Cells and Decreases with Extensive Expansion of the Cells

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