Chunmeng Shi

Third Military Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (50)234.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The in vivo flow cytometry (IVFC) is now a powerful technique in biomedical research, especially for tracking specific cells in circulatory system. The current fluorescence-based IVFC is limited to visible spectrum, while near infrared (NIR) dyes have their advantages, such as deeper penetration, less absorption and less scattering for NIR fluorescence. Here, using an NIR in vivo flow cytometer with a 785 nm laser excitation, the measurement of fluorescent dye IR-780 labeled circulating cells is demonstrated. Representative peaks corresponding to NIR fluorescent circulating cells are detected and quantified. In addition, blood flow information, including the blood flow velocity and flow volume per unit time, is obtained. By simultaneous detection of IR-780 and enhanced green fluorescent protein (EGFP) signals from dual labeled cells, the IR-780 is shown to be a suitable fluorescent dye for multicolor detection by IVFC, including NIR. Thus, the IVFC is extended to the NIR range and shows potential application in biomedical research. © 2015 International Society for Advancement of Cytometry. © 2015 International Society for Advancement of Cytometry.
    Cytometry Part A 07/2015; DOI:10.1002/cyto.a.22711 · 3.07 Impact Factor
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    Zelin Chen · Tingyu Dai · Xia Chen · Li Tan · Chunmeng Shi
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    ABSTRACT: Skin as the largest and easily accessible organ of the body represents an abundant source of adult stem cells. Among them, dermal stem cells hold great promise in tissue repair and the skin granulation tissue has been recently proposed as a promising source of dermal stem cells, but their biological characteristics have not been well investigated. The 5-bromo-2'-deoxyuridine (BrdU) lineage tracing approach was employed to chase dermal stem cells in vivo. Granulation tissue derived cells (GTCs) were isolated and their in vitro proliferation, self-renewing, migration, and multi-differentiation capabilities were assessed. Combined radiation and skin wound model was used to investigate the therapeutic effects of GTCs. MicroRNA-21 (miR-21) antagomir was used to antagonize miR-21 expression. Reactive oxygen species (ROS) were scavenged by N-acetyl cysteine (NAC). The quiescent dermal stem/progenitor cells were activated to proliferate upon injury and enriched in granulation tissues. GTCs exhibited enhanced proliferation, colony formation and multi-differentiation capacities. Topical transplantion of GTCs into the combined radiation and skin wound mice accelerated wound healing and reduced tissue fibrosis. Blockade of the miR-21 expression in GTCs inhibited cell migration and differentiation, but promoted cell proliferation and self-renewing at least partiallyvia a ROS dependent pathway. The granulation tissue may represent an alternative adult stem cell source in tissue replacement therapy and miR-21 mediated ROS generation negatively regulates the stemness-related properties of granulation tissue derived cells.
    Stem Cell Research & Therapy 04/2015; 6(1):85. DOI:10.1186/s13287-015-0070-9 · 4.63 Impact Factor
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    Tao Liu · Shenglin Luo · Yang Wang · Xu Tan · Qingrong Qi · Chunmeng Shi
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    ABSTRACT: Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for cancer imaging and detection in living systems. However, cancer NIR fluorescent sensors are very challenging to develop because they are required to exhibit good specificity and low toxicity as an eligible contrast agent. Here, we describe the synthesis of a new heptamethine indocyanine dye (NIR-27) modified with a glycine at the end of each N-alkyl side chain, and its biological characterization for in vivo cancer-targeted NIR imaging. In addition to its high specificity, NIR-27 also shows lower cytotoxicity than indocyanine green, a nonspecific NIR probe widely used in clinic. These characteristics suggest that NIR-27 is a promising prospect as a new NIR fluorescent sensor for sensitive cancer detection.
    Drug Design, Development and Therapy 09/2014; 8:1287-97. DOI:10.2147/DDDT.S65696 · 3.03 Impact Factor
  • Zelin Chen · Yu Wang · Chunmeng Shi
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    ABSTRACT: Skin, the largest organ of the body, is a promising reservoir for adult stem cells. The epidermal stem cells and hair follicle stem cells have been well studied for their important roles in homeostasis, regeneration and repair of the epidermis and appendages for decades. However, stem cells resided in dermis were not identified until the year 2001, when a variety of stem cells subpopulations have been isolated and identified from the dermis of mammalian skin such as neural crest stem cells, mesenchymal stem cell (MSC)-like dermal stem cells and dermal hematopoietic cells. And these stem cell subpopulations exhibited capabilities of self-renewing, multi-potent differentiating, and immunosuppressive properties. Hence, the dermis derived stem cells showed extensive potential applications in regenerative medicine especially for wound healing/tissue repair, neural repair, and hematopoietic recovery. Here, we summarized current research on the stem cell subpopulations derived from the dermis, and aimed to provide a comprehensive review on their isolation, specific markers, differentiation capacity, and the functional activities in homeostasis, regeneration and tissue repair.
    Cell Transplantation 06/2014; 24(8). DOI:10.3727/096368914X682431 · 3.57 Impact Factor
  • Yang Wang · Tao Liu · Erlong Zhang · Shenglin Luo · Xu Tan · Chunmeng Shi
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    ABSTRACT: Personalized oncology significantly relies on the development of theranostic agents to integrate cancer therapeutics and diagnostics. Current strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer specific ligands, contrast agents and therapeutic drugs. In this study, we reported a near infrared (NIR) heptamethine indocyanine dye, IR-780, which selectively accumulated in the mitochondria of drug-resistant human lung cancer cells (A549/DR) and significantly inhibited cell growth, self-renewal and migration without the need of any chemical conjugation. IR-780 was also able to induce A549/DR cell apoptosis by disrupting the mitochondrial function. Furthermore, IR-780 dye exhibited remarkable tumoricidal activity and inhibited tumor recurrence in mouse syngeneic Lewis lung carcinoma xenograft model. With the unique properties of targeting, near infrared imaging and inhibitive effect to the drug-resistant cancer cells both in vitro and in vivo, IR-780 may represent a potential theranostic agent for tumor recurrence.
    Biomaterials 02/2014; 35(13). DOI:10.1016/j.biomaterials.2014.01.061 · 8.31 Impact Factor
  • Li Gao · Fei Liu · Li Tan · Tao Liu · Zelin Chen · Chunmeng Shi
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    ABSTRACT: Mesenchymal stromal cells (MSCs) have been developed for the prevention and treatment of graft-versus-host disease (GVHD). Non-cultured natural MSCs are considered ideal, as they better maintain their biological and therapeutic properties. The skin is the largest organ in the body and constitutes an interesting alternative to bone marrow for the generation of MSCs. Large numbers of dermal-derived-MSCs (DMSCs) can be easily generated without culturing in vitro, but their therapeutic effects still remain unclear. In this study, we described for the first time the use of non-cultured DMSCs for controlling GVHD in an MHC-mismatched mouse model and investigated their immunomodulatory effects. Our results showed that non-cultured mouse DMSCs decreased the incidence and severity of acute GVHD during MHC-mismatched stem cell transplantation in mice. This effect was mediated by the inhibition of splenic cell (SPC) proliferation and the enhancement of Treg cells. Consistent with the results in vivo, the results in vitro showed that human DMSCs inhibited the proliferation of peripheral blood mononuclear cells (PBMCs) by inhibiting the proliferation of CD3(+) T cells. hDMSCs prevented PBMCs from entering S phase, suppressed the activation of CD3(+) T cells and increased Treg proportions. In conclusion, DMSCs should be considered as a novel MSC source for the control of refractory GVHD.
    Biomaterials 01/2014; 35(11). DOI:10.1016/j.biomaterials.2014.01.008 · 8.31 Impact Factor
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    ABSTRACT: In this paper, a novel and useful method based on photolysis of silver chloride is presented for the preparation of silver nanoparticles. Silver nanoparticles can be prepared by using silver nitrate and commercially available carboxymethyl chitosan under solar irradiation. This method is based on the photolysis of silver chloride. The stabilizing effect of carboxymethyl chitosan allows for the stable storage of these silver nanoparticles in the reaction mixture for more than six months; further, nanoparticles of different sizes can be separated from each other just by centrifugation. The favorable properties of carboxymethyl chitosan facilitate the use of these nanoparticles without further purification.
    Materials Letters 12/2013; 112:101-104. DOI:10.1016/j.matlet.2013.09.035 · 2.27 Impact Factor
  • Erlong Zhang · Shenglin Luo · Xu Tan · Chunmeng Shi
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    ABSTRACT: IR-780 iodide, a near-infrared fluorescent heptamethine dye, has been recently characterized to exhibit preferential accumulation property in the mitochondria of tumor cells. In this study, we investigated the possible mechanisms for its tumor selective activity and its potential as a drug delivery carrier. Results showed that the energy-dependent uptake of IR-780 iodide into the mitochondria of tumor cells was affected by glycolysis and plasma membrane potential. Moreover, OATP1B3 subtype of organic anion transporter peptides (OATPs) may play a dominant role in the transportation of IR-780 iodide into tumor cells, while cellular endocytosis, mitochondrial membrane potential and the ATP-binding cassette transporters did not show significant influence to its accumulation. We further evaluated the potential of IR-780 iodide as a drug delivery carrier by covalent conjugation of IR-780 with nitrogen mustard (IR-780NM). In vivo imaging showed that IR-780NM remained the tumor targeting property, indicating that IR-780 iodide could be potentially applied as a drug delivery agent for cancer targeted imaging and therapy.
    Biomaterials 10/2013; 35(2). DOI:10.1016/j.biomaterials.2013.10.033 · 8.31 Impact Factor
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    ABSTRACT: Highly charged hydrophilic superparamagnetic Fe3O4 colloidal nanocrystal clusters with an average diameter of 195 nm have been successfully synthesized using a modified one-step solvothermal method. Anionic polyelectrolyte poly(4-styrenesulfonic acid-co-maleic acid) sodium salt containing both sulfonate and carboxylate groups was used as the stabilizer. The clusters synthesized under different experimental conditions were characterized with transmission electron microscopy and dynamic light scattering; it was found that the size distribution and water dispersity were significantly affected by the concentration of the polyelectrolyte stabilizer and iron sources in the reaction mixtures. A possible mechanism involving novel gel-like large molecular networks that confined the nucleation and aggregation process was proposed and discussed. The colloidal nanocrystal clusters remained negatively charged in the experimental pH ranges from 2 to 11, and also showed high colloidal stability in phosphate buffered saline (PBS) and ethanol. These highly colloidal stable superparamagnetic Fe3O4 clusters could find potential applications in bioseparation, targeted drug delivery, and photonics.
    Nanoscale 06/2013; 5(15). DOI:10.1039/c3nr00931a · 7.39 Impact Factor
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    Qinyuan Guo · Shenglin Luo · Qingrong Qi · Chunmeng Shi
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    ABSTRACT: Our research has identified a couple of near-infrared (NIR) heptamethine indocyanine dyes exhibiting preferential tumor accumulation property for in vivo imaging. On the basis of our foregoing work, we describe here a preliminary structure–activity relationship (SAR) study of 11 related heptamethine indocyanine dyes and several essential requirements of these structures for in vivo tumor-targeted imaging.
    Journal of Innovative Optical Health Sciences 02/2013; 06(01). DOI:10.1142/S179354581350003X · 0.93 Impact Factor
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    ABSTRACT: Personalized oncology significantly relies on the development of cancer theranostic agents to integrate cancer therapeutics and diagnostics. Current most common strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer targeted ligands, contrast agents and therapeutic agents. Here we report the chemical synthesis and biological characterization of a new heptamethine dye, termed as IR-808DB, natively with multifunctional characteristics of cancer targeting, near-infrared fluorescence imaging, and efficient anticancer activity. The tumor inhibition effect of IR-808DB is higher than that of cyclophosphamide (CTX) toward a broad spectrum of tumor xenograft models. These findings provide IR-808DB a promising prospect as a new cancer theranostic agent that would enable integration of cancer targeted therapeutics and diagnostics without requirement of multi-component chemical conjugation.
    Biomaterials 12/2012; 34(9). DOI:10.1016/j.biomaterials.2012.11.057 · 8.31 Impact Factor
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    ABSTRACT: With the clarification of the important roles of microRNAs (miRNAs) in diverse physiologic and pathologic processes, the effects of miRNAs in wound healing have attracted more attention recently. However, the global pattern of miRNA expression in wound tissue is still unknown. In the present study, we depicted the miRNA profile and identified at least 54 miRNAs, including miR-21, changed for more than twofold at the stage of granulation formation during wound healing. These miRNAs were closely related to the major events of wound healing, including cell migration and proliferation, angiogenesis, and matrix remolding. Furthermore, we found that miR-21 was up-regulated after skin injury, mainly in activated and migrating epithelial cells of epidermis and mesenchymal cells of dermis. Locally antagonizing miR-21 by directly injecting antagomir to wound edge caused significant delay of wound closure with impaired collagen deposition. Unexpectedly, we found wounds treated with miR-21 antagomir had an obvious defect in wound contraction at an early stage of wound healing. The significant role of miR-21 in wound contraction was further confirmed by in vivo gain-of-function and in vitro loss-of-function experiments. In conclusion, the present study has for the first time depicted miRNA profiling of wound healing and demonstrated the involvement of miR-21 in regulating the wound contraction and collagen deposition. These results suggest that miR-21 may be a new medical target in skin wound manipulation.
    American Journal Of Pathology 12/2012; 181(6):1911-20. DOI:10.1016/j.ajpath.2012.08.022 · 4.60 Impact Factor
  • Dechun Wang · Shuguang Wang · Chunmeng Shi
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    ABSTRACT: Mesenchymal stem cells (also known as multipotent stromal cells, MSCs) are considered as promising candidate cells for stem cell-based therapy. However, the applications of MSCs are facing controversial concerns of potential tumorigenic risks. There is also increasing evidence that MSCs may play a modulatory role in the development and progression of tumors. MSCs have the potential to migrate to tumor sites and promote tumor cell proliferation, invasion and metastasis. In addition to these risks, MSCs also have shown to be an attractive target for gene/cell-mediated anti-tumor therapy. These complicated behaviors of MSCs in cancer warrant further study to evaluate the benefits of MSCs treatment and the long-term risk of tumor origin or incidence from MSCs under different pathological conditions.
    Current Stem Cell Research & Therapy 02/2012; 7(5):370-80. DOI:10.2174/157488812802481454 · 2.86 Impact Factor
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    ABSTRACT: The future personalized oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging, and cytotoxic activities. In our recent study, we have recently identified a near infrared fluorescent heptamethine dye, IR-780, with unexpected preferential accumulation in a broad spectra of tumor cells for in vivo tumor targeting and imaging. On the basis of this foregoing work, in this study, we describe here the chemical synthesis and biological characterization of an analog of IR-780, termed as IR-808, which not only possesses similar tumor targeting and imaging properties of IR-780, but also has unique photodependent cytotoxic activity. In addition, IR-808 also exhibits favorable optical and pharmacokinetic properties, as well as good biocompatibility. This dye may hold promise as a candidate multifunctional theranostic agent for future tumor targeted imaging and photodynamic therapy.
    Biomaterials 12/2011; 33(7):2230-9. DOI:10.1016/j.biomaterials.2011.11.081 · 8.31 Impact Factor
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    ABSTRACT: The transforming growth factor-β (TGF-β) signaling pathway plays important roles in maintaining normal tissue homeostasis, and is tightly controlled by a network of biomolecules. MicroRNAs (miRNAs) are small noncoding RNAs of ∼22 nucleotides that regulate gene expression at posttranscriptional levels. Increasing evidence points to the important role of miRNAs in TGF-β signaling. OncomicroRNA miR-21 has been established as a key regulator of mesenchymal phenotype transition induced by TGF-β. However, the effects of miR-21 on epithelial biology involved in TGF-β signaling pathway such as cytostatic program and epithelial to mesenchymal transition (EMT) processes are unclear. Here we show that miR-21 is upregulated after TGF-β exposure in both growth inhibition and EMT models of HaCaT keratinocytes. To determine the potential roles of miR-21 in TGF-β-induced growth-arrest and EMT models, we showed that ectopic expression of miR-21 overcame TGF-β' growth-inhibitory effect and the knockdown of miR-21 potentialized this effect, but perturbation of miR-21 levels had little effect on EMT. Moreover, TGFBR2, PTEN, PDCD4, and TAp63 were identified as targets of miR-21 in HaCaT cells. And among them, TGFBR2, PTEN, and TAp63 were associated with TGF-β-induced cytostatic program. Thus, our results suggest that miR-21 regulates the ability of epithelial cells to respond to TGF-β, with potential impact on epithelium homeostasis, wound-healing and tumorigenesis.
    The international journal of biochemistry & cell biology 11/2011; 44(2):366-76. DOI:10.1016/j.biocel.2011.11.012 · 4.24 Impact Factor
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    ABSTRACT: The development of multifunctional agents for simultaneous tumor targeting and near infrared (NIR) fluorescence imaging is expected to have significant impact on future personalized oncology owing to the very low tissue autofluorescence and high tissue penetration depth in the NIR spectrum window. Cancer NIR molecular imaging relies greatly on the development of stable, highly specific and sensitive molecular probes. Organic dyes have shown promising clinical implications as non-targeting agents for optical imaging in which indocyanine green has long been implemented in clinical use. Recently, significant progress has been made on the development of unique NIR dyes with tumor targeting properties. Current ongoing design strategies have overcome some of the limitations of conventional NIR organic dyes, such as poor hydrophilicity and photostability, low quantum yield, insufficient stability in biological system, low detection sensitivity, etc. This potential is further realized with the use of these NIR dyes or NIR dye-encapsulated nanoparticles by conjugation with tumor specific ligands (such as small molecules, peptides, proteins and antibodies) for tumor targeted imaging. Very recently, natively multifunctional NIR dyes that can preferentially accumulate in tumor cells without the need of chemical conjugation to tumor targeting ligands have been developed and these dyes have shown unique optical and pharmaceutical properties for biomedical imaging with superior signal-to-background contrast index. The main focus of this article is to provide a concise overview of newly developed NIR dyes and their potential applications in cancer targeting and imaging. The development of future multifunctional agents by combining targeting, imaging and even therapeutic routes will also be discussed. We believe these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis and therapeutics for the treatment of cancer.
    Biomaterials 07/2011; 32(29):7127-38. DOI:10.1016/j.biomaterials.2011.06.024 · 8.31 Impact Factor
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    ABSTRACT: The development of multifunctional agents that could be used for simultaneous tumor targeting, imaging and treatment is a major goal in cancer research and is expected to contribute significantly to the realization of personalized oncology. Mitochondria are involved in diverse physiological activities and confer vital roles in cancer development and progression. Increasing efforts are being made to develop cancer treatment strategies based on various mitochondrial targets and novel mitochondrial drug delivery systems. Multifunctional nanostructures or multifunctional chemical compounds further broaden the current concept of tumor targeting and provide alternative solutions for mitochondrially targeted cancer therapy.
    Drug discovery today 02/2011; 16(3-4):140-6. DOI:10.1016/j.drudis.2010.12.006 · 5.96 Impact Factor
  • Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology; 11/2010
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    ABSTRACT: Near-infrared (NIR) fluorescent agents hold great promise for noninvasive in vivo imaging. We have recently reported that a NIR fluorescent heptamethine dye, IR-780 iodide, exhibits unique optical properties for biomedical imaging. On the basis of this foregoing work, we further describe here the potential application of IR-780 iodide as a novel NIR agent for stem cell labeling and tracking. The labeling efficiency, subcellular localization, and the effects on cell viability and differentiation of IR-780 iodide were investigated. The in vivo distribution of stem cells after intravenous transplantation was traced by whole-body animal NIR imaging. Our results showed that IR-780 iodide exhibited superior labeling efficiency and biocompatibility with unique optical properties. Following whole-body NIR imaging, the pulmonary passage of stem cells was noninvasively visualized in rats after systemic transplantation of IR-780 iodide-labeled stem cells through intravenous delivery. With this NIR imaging method, we further confirmed that pretreatment with sodium nitroprusside (SNP), a vasodilator agent, significantly reduced the cell trapping in the lung and increased the cell passage through the lung capillaries. Our study suggests that IR-780 iodide may represent an effective NIR fluorophore for stem cell labeling and tracking.
    Cell Transplantation 11/2010; 20(5):741-51. DOI:10.3727/096368910X536536 · 3.57 Impact Factor
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    ABSTRACT: Near-infrared (NIR) fluorescence imaging holds great promise for tumor imaging due to low tissue autofluorescence and deep tissue penetration. However, most tumor-targeting fluorescent probes require combination of targeting agents and fluorescent reporters. In this study, we described a NIR heptamethine cyanine dye, IR-780 iodide, with preferential accumulation in multiple tumor cells without the necessity of chemical conjugation. The IR-780 iodide was found to retain in tumors but not normal cells in multiple tumor xenografts in nude mice and chemically-induced lung tumors in C57BL/6 mice. The fluorescent signal of tumors could persist at least 20 days with a significant signal-to-background ratio. As a lipophilic cation, a predominant accumulation of IR-780 iodide was shown in the mitochondria of tumor cells owing to the high magnitude of mitochondrial membrane potential in tumor cells than normal cells. We further showed that the transportation of IR-780 iodide into tumor cells was mediated by the organic anion transporter peptides (OATPs) because the dye accumulation was significantly inhibited by sulfobromophthalein (BSP), a competitive inhibitor of OATPs. Our study shows that IR-780 iodide that preferentially accumulates in tumor cells and is natively NIR fluorescent would be useful in tumor detection.
    Biomaterials 09/2010; 31(25):6612-7. DOI:10.1016/j.biomaterials.2010.05.007 · 8.31 Impact Factor

Publication Stats

993 Citations
234.98 Total Impact Points

Institutions

  • 2000–2015
    • Third Military Medical University
      • Institute of Pathology and Southwest Cancer Center
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2013
    • Sichuan University
      • Department of Medicinal Chemistry
      Hua-yang, Sichuan, China
  • 2012
    • Xinqiao Hospital
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2008–2009
    • Emory University
      • Department of Urology
      Atlanta, GA, United States