Human adipose tissue derived mesenchymal stem cells are resistant to several chemotherapeutic agents

Liang, Wei; Xia, Hailong; Li, Jing; Zhao, Robert Chunhua

doi:10.1007/s10616-011-9374-5

Cited by 43 publications

(36 citation statements)

References 25 publications

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“…Therefore, the selection could also be due to the high-antibiotic and starvation steps used for the culture of the cells. In fact, the intrinsic feature of MSCs is resistance to injury, including its high resistance to xenobiotics (36,46). Furthermore, it has recently been described that, under severe cellular stress conditions, it is possible to isolate multipotent cells from adipose tissue (25); our approach could be considered a stressful method, taking into account the high antibiotic- Under the in vitro culture conditions described, pAVPCs share some features with pericytes in term of antigen expression (18), such as the expression of the proteoglycan NG2, a marker exclusively associated with the arterial system (16).…”

Section: Resultsmentioning

confidence: 99%

Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

Zaniboni

Bernardini

Alessandri

et al. 2014

American Journal of Physiology-Cell Physiology

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Several studies have already described the presence of specialized niches of precursor cells in vasculature wall, and it has been shown that these populations share several features with mesenchymal stromal cells (MSCs). Considering the relevance of MSCs in the cardiovascular physiopathology and regenerative medicine, and the usefulness of the pig animal model in this field, we reported a new method for MSC-like cell isolation from pig aorta. Filling the vessel with a collagenase solution for 40 min, all endothelial cells were detached and discarded and then collagenase treatment was repeated for 4 h to digest approximately one-third of the tunica media. The ability of our method to select a population of MSC-like cells from tunica media could be ascribed in part to the elimination of contaminant cells from the intimal layer and in part to the overnight culture in the high antibiotic/antimycotic condition and to the starvation step. Aortic-derived cells show an elongated, spindle shape, fibroblast-like morphology, as reported for MSCs, stain positively for CD44, CD56, CD90, and CD105; stain negatively for CD34 and CD45; and express CD73 mRNA. Moreover, these cells show the classical mesenchymal trilineage differentiation potential. Under our in vitro culture conditions, aortic-derived cells share some phenotypical features with pericytes and are able to take part in the formation of network-like structures if cocultured with human umbilical vein endothelial cells. In conclusion, our work reports a simple and highly suitable method for obtaining large numbers of precursor MSC-like cells derived from the porcine aortic wall.

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Section: Resultsmentioning

confidence: 99%

Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

Zaniboni

Bernardini

Alessandri

et al. 2014

American Journal of Physiology-Cell Physiology

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“…7 Moreover, several studies demonstrated the inherent chemoresistant properties of the MSC that enable them to withstand the suicide effect and thus prolong the bystander toxicity exerted on the neighboring tumor cells. [8][9][10] One of the most frequently used enzyme/prodrug combinations in GDEPT still remains the Herpes simplex virus thymidine kinase (HSV-TK) in combination with prodrug ganciclovir (GCV). 1 HSV-TK was expressed in the MSC and demonstrated an antitumor efficiency in the preclinical models either alone 11,12 or in combination with a valproic acid as an augmentation agent.…”

Section: Introductionmentioning

confidence: 99%

Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in human melanoma xenograft model

et al. 2014

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Mesenchymal stromal cells (MSC) can be exploited as cellular delivery vehicles for the enzymes converting non-toxic prodrugs to toxic substances. Because of their inherent chemoresistance, they exert potent bystander and antitumor effect. Here we show that the human adipose tissue-derived MSC expressing fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) in combination with 5-fluorocytosine (5FC) mediated a long-term tumor-free survival in the 83.3% of tumor-bearing animals. CD-MSC/5FC treatment induced cytotoxicity against model human melanoma cells EGFP-A375. Only 4% of the therapeutic CD-MSC cells eliminated >98.5% of the tumor cells in vitro. Long-term tumor-free survival was confirmed in 15 out of the 18 animals. However, repeatedly used CD-MSC/5FC therapeutic regimen generated more aggressive and metastatic variant of the melanoma cells EGFP-A375/Rel3. These cells derived from the refractory xenotransplants exhibited increased resistance to the CD-MSC/5FC treatment, altered cell adhesion, migration, tumorigenic and metastatic properties. However, long-term curative effect was achieved by the augmentation of the CD-MSC/5FC regimen along with the inhibition of c-Met/hepatocyte growth factor signaling axis in this aggressive melanoma derivative. In summary, the CD-MSC/5FC regimen can be regarded as a very effective antitumor approach to achieve long-term tumor-free survival as demonstrated on a mouse model of aggressive human melanoma xenografts.

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“…While the effects of chemotherapeutics on bone marrow stem cells (BMSCs) and hematopoietic stem cells have been studied for a number of years (Gardner, et al, 1993; J. Li, et al, 2004), researchers have only recently begun investigating the effects of these drugs on adipose-derived stem cells (ASCs) (Liang, et al, 2011; Zimmerlin, et al, 2011). Advancements in drug formulations have resulted in increased patient survival, but unfortunately many of these chemotherapeutics also have severe side effects, such as long-term musculoskeletal damage (Schriock, et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

Beane

Fonseca

Darling

2014

Experimental Cell Research

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In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 M. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy.

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Human adipose tissue derived mesenchymal stem cells are resistant to several chemotherapeutic agents

Cited by 43 publications

References 25 publications

Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in human melanoma xenograft model

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

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