Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool

García‐Castro, Javier; Trigueros, César; Madrenas, Joaquı́n; Pérez-Simón, Josè Antonio; Rodrı́guez, René; Menéndez, Pablo

doi:10.1111/j.1582-4934.2008.00516.x

Cited by 126 publications

(93 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Increasing evidence indicates that MSCs might constitute the target cell for transforming mutations responsible for sarcoma development, suggesting that MSCs/ASCs may become an instrumental tool in studies aimed at dissecting the pathogenesis and cellular origin of sarcomas [1]. It has been demonstrated that BM-mMSCs provided a permissive environment for tumoral transformation and sarcoma development mediated by several sarcoma-associated fusion genes [2][3][4][5].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

FUS-CHOP Fusion Protein Expression Coupled to p53 Deficiency Induces Liposarcoma in Mouse but Not in Human Adipose-Derived Mesenchymal Stem/Stromal Cells

et al. 2011

View full text Add to dashboard Cite

Human sarcomas have been modeled in mice by expression of specific fusion genes in mesenchymal stem cells (MSCs). However, sarcoma models based on human MSCs are still missing. We attempted to develop a model of liposarcoma by expressing FUS (FUsed in Sarcoma; also termed TLS, Translocated in LipoSarcoma)-CHOP (C/ EBP HOmologous Protein; also termed DDIT3, DNA Damage-Inducible Transcript 3), a hallmark mixoid liposarcoma-associated fusion oncogene, in wild-type and p53-deficient mouse and human adipose-derived mesenchymal stem/stromal cells (ASCs). FUS-CHOP induced liposarcoma-like tumors when expressed in p53 2/2 but not in wild-type (wt) mouse ASCs (mASCs). In the absence of FUS-CHOP, p53 2/2 mASCs forms leiomyosarcoma, indicating that the expression of FUS-CHOP redirects the tumor genesis/phenotype. FUS-CHOP expression in wt mASCs does not initiate sarcomagenesis, indicating that p53 deficiency is required to induce FUS-CHOP-mediated liposarcoma in fat-derived mASCs. In a human setting, p53-deficient human ASCs (hASCs) displayed a higher in vitro growth rate and a more extended lifespan than wt hASCs. However, FUS-CHOP expression did not induce further changes in culture homeostasis nor initiated liposarcoma in either wt or p53-depleted hASCs. These results indicate that FUS-CHOP expression in a p53-deficient background is sufficient to initiate liposarcoma in mouse but not in hASCs, suggesting the need of additional cooperating mutations in hASCs. A microarray gene expression profiling has shed light into the potential deregulated pathways in liposarcoma formation from p53-deficient mASCs expressing FUS-CHOP, which might also function as potential cooperating mutations in the transformation process from hASCs. STEM CELLS 2011; 29:179-192 Disclosure of potential conflicts of interest is found at the end of this article.

show abstract

Section: Discussionmentioning

confidence: 99%

“…It is becoming evident that mesenchymal stem cells (MSCs) may be the target cell in which transforming mutations responsible for sarcoma development arise [1]. Several types of sarcomas have been reproduced in vivo on overexpression of specific fusion oncoproteins in bone marrow (BM)-derived mouse MSCs (mMSCs).…”

Section: Introductionmentioning

confidence: 99%

FUS-CHOP Fusion Protein Expression Coupled to p53 Deficiency Induces Liposarcoma in Mouse but Not in Human Adipose-Derived Mesenchymal Stem/Stromal Cells

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The onset and progression of hematological malignancies are in many cases dependent on mutual interactions between the leukemic blasts/plasma cells and BM stroma/MSCs, which provide survival and growth-promoting signals [8,95,96]. Interestingly, the fusion MLL-AF4 was recently found expressed in both BM-MSCs and leukemic blasts in 100% of infants suffering from pro-B ALL highlighting an unrecognized role of the BM milieu in the pathogenesis of this dismal infant leukemia [97].…”

Section: Mscs and Tumor Growthmentioning

confidence: 99%

“…Thus, cultures are heterogeneous in potency and it is likely that only a small MSC subset represents the bona fide multipotent stem cell population. The potential of MSCs for cell-based therapies relies on several key properties: (i) capacity to differentiate into several cell lineages; (ii) lack of immunogenicity; (iii) immunomodulatory properties; (iv) robust ex vivo expansion potential; (v) ability to secrete factors, which regulate cell proliferation, differentiation and migration and; (vi) homing ability to damaged tissues and tumor sites [8]. Due to these properties, MSCs are being used worldwide in a variety of clinical applications including tissue repair, treatment of graft-versus-host disease and autoimmune diseases and are being used as vehicles to deliver anti-cancer therapies [8].…”

Section: Introductionmentioning

confidence: 99%

Modeling sarcomagenesis using multipotent mesenchymal stem cells

2011

View full text Add to dashboard Cite

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.

show abstract

“…Mesenchymal stem cell (MSC) immunoregulatory effects and allogenic tolerance 1 led to investigations into the treatment of severe immune‐mediated diseases 2, which in turn attracted interest on anti‐inflammatory MSCs as a potential asthma treatment. However, the use of MSCs for asthma may face significant limitations.…”

mentioning

confidence: 99%

Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma

Mariñas-Pardo

Mirones

Amor-Carro

et al. 2014

Allergy

View full text Add to dashboard Cite

BackgroundMesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti‐inflammatory therapy may favor airway remodeling and therefore be detrimental.MethodsAdipose tissue‐derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite‐instilled animals receiving intravenous vehicle or phosphate‐buffered saline‐instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge.ResultsThe mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T‐helper‐1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues.ConclusionsTherapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro‐remodeling effects and ameliorates airway hyper‐responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell‐based asthma therapies, although caution and solid preclinical data building are warranted.

show abstract

Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool

Cited by 126 publications

References 138 publications

FUS-CHOP Fusion Protein Expression Coupled to p53 Deficiency Induces Liposarcoma in Mouse but Not in Human Adipose-Derived Mesenchymal Stem/Stromal Cells

FUS-CHOP Fusion Protein Expression Coupled to p53 Deficiency Induces Liposarcoma in Mouse but Not in Human Adipose-Derived Mesenchymal Stem/Stromal Cells

Modeling sarcomagenesis using multipotent mesenchymal stem cells

Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma

Contact Info

Product

Resources

About