A Comparison of Proteins Expressed between Human and Mouse Adipose-Derived Mesenchymal Stem Cells by a Proteome Analysis through Liquid Chromatography with Tandem Mass Spectrometry

Nahar, Saifun; Nakashima, Yoshiki; Miyagi-Shiohira, Chika; Kinjo, Takao; Kobayashi, Naoya; Saitoh, Issei; Watanabe, Masami; Noguchi, Hirofumi; Fujita, Jiro

doi:10.3390/ijms19113497

Cited by 12 publications

(5 citation statements)

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“…Indeed, a recent proteomic study showed that 92% of proteins in adipose-derived mesenchymal stem cells of mouse and human are consistent. 60 We also added minimal details to the interactions of Met and α5β1 to be able to study the effect of AXT050 that targets and breaks the interaction of α5β1 with Met. HGF-independent activation of Met from binding of α5β1 to fibronectin 22 was neglected in this model due to lack of sufficient experimental data, but could be implemented in the future.…”

Section: Discussionmentioning

confidence: 99%

Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

et al. 2019

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Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met–integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients.

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Section: Discussionmentioning

confidence: 99%

Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

et al. 2019

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“…Integrin β1 expression is important for mice MSCs migration, while C-X-C chemokine receptor type 4 expression is involved for human MSC migration to sites of tissue injury[ 24 - 25 ]. It has been demonstrated that 92% of MSC protein expression is similar in humans and mice[ 26 ]. MSCs represent only a small proportion of the cells in bone marrow, and their proliferation and differentiation capacity correlates inversely with age[ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

Bahrehbar¹,

Valojerdi²,

Esfandiari³

et al. 2020

WJSC

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BACKGROUND Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. According to previous reports, various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Human embryonic stem cells (ES) provide an alternative source for mesenchymal stem cells (MSCs) because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics. Embryonic stem cell-derived mesenchymal stem cells (ES-MSCs) are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs. However, possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated. AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells (BM-MSCs) in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure. METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF. Either human ES-MSCs or BM-MSCs were transplanted into these mice. Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ES-MSCs and/or BM-MSCs, we evaluated body weight, estrous cyclicity, follicle-stimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation. Moreover, terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling, real-time PCR, Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation. Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor, insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function. RESULTS The human ES-MSCs significantly restored hormone secretion, survival rate and reproductive function in POF mice, which was similar to the results obtained with BM-MSCs. Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles. Notably, the transplanted mice generated new offspring. The results of different analyses showed increases in antiapoptotic and trophic proteins and genes. CONCLUSION These results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility. The possible mechanisms of human ES-MSC were related to promotion of follicular dev...

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“…Some researchers have analyzed the contents of extracellular vesicles released by adipose tissue-derived MSCs [8,46]. Others have performed secretome analysis with low-resolution techniques, which has not provided exhaustive information [47,48].…”

Section: Discussionmentioning

confidence: 99%

A comparative study on normal and obese mice indicates that the secretome of mesenchymal stromal cells is influenced by tissue environment and physiopathological conditions

Ayaz-Güner

Alessio

Acar

et al. 2020

Preprint

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BackgroundThe term mesenchymal stromal cells (MSCs) designates an assorted cell population comprised of stem cells, progenitor cells, fibroblasts, and stromal cells. MSCs contribute to the homeostatic maintenance of many organs through paracrine and long-distance signaling.Tissue environment, in both physiological and pathological conditions, may affect the intercellular communication of MSCs. MethodsWe performed a secretome analysis of MSCs isolated from subcutaneous adipose tissue (sWAT) and visceral adipose tissue (vWAT), and from bone marrow (BM), of normal and obese mice.ResultsThe MSCs isolated from tissues of healthy mice share a common core of released factors: components of cytoskeletal and extracellular structures; regulators of basic cellular functions, such as protein synthesis and degradation; modulators of endoplasmic reticulum stress; and counteracting oxidative stress. It can be hypothesized that MSC secretome beneficially affects target cells by the horizontal transfer of many released factors. Each type of MSC may exert specific signaling functions, which could be determined by looking at the many factors that are exclusively released from every MSC type.The vWAT-MSCs release factors that play a role in detoxification activity in response to toxic substances and drugs. The sWAT-MSC secretome contains proteins involved in in chondrogenesis, osteogenesis, and angiogenesis. Analysis of BM-MSC secretome revealed that these cells exert a signaling function by remodeling extracellular matrix structures, such as those containing glycosaminoglycans. Obesity status profoundly modified the secretome content of MSCs, impairing the above-described activity and promoting the release of inflammatory factors.ConclusionWe demonstrated that the content of MSC secretomes depends on tissue microenvironment and that pathological condition may profoundly alter its composition.

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A Comparison of Proteins Expressed between Human and Mouse Adipose-Derived Mesenchymal Stem Cells by a Proteome Analysis through Liquid Chromatography with Tandem Mass Spectrometry

Cited by 12 publications

References 35 publications

Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

A comparative study on normal and obese mice indicates that the secretome of mesenchymal stromal cells is influenced by tissue environment and physiopathological conditions

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