| 1. |
- Lee, Chyan-Jang, et al.
(author)
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Cathelicidin LL-37 and HSV-1 Corneal Infection : Peptide Versus Gene Therapy
- 2014
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In: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology. - 2164-2591. ; 3:3, s. 1-14
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate the potential utility of collagen-based corneal implants with anti?Herpes Simplex Virus (HSV)-1 activity achieved through sustained release of LL-37, from incorporated nanoparticles, as compared with cell-based delivery from model human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37. Methods: We tested the ability of collagen-phosphorylcholine implants to tolerate the adverse microenvironment of herpetic murine corneas. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs to confer viral resistance, and their response to HSV-1 infection was examined. Results: Our implants remained in herpetic murine corneas 7 days longer than allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size. Conclusion: LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti?HSV-1 activity by blocking binding. However, while both slowed down virus spread, neither was able on its own to completely inhibit the viruses. Translational Relevance: LL-37 releasing hydrogels may have potential utility as corneal substitutes for grafting in HSV-1 infected corneas, possibly in combination with LL-37 producing therapeutic cells.
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| 2. |
- Rajendran, Vijayalakshmi, et al.
(author)
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In vitro tumorigenic assay : colony forming assay for cancer stem cells
- 2018
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In: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1692, s. 89-95, s. 89-95
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Book chapter (peer-reviewed)abstract
- Colony forming or clonogenic assay is an in vitro quantitative technique to examine the capability of a single cell to grow into a large colony through clonal expansion. Clonogenic activity is a sensitive indicator of undifferentiated cancer stem cells. Here, we described the colony forming ability of the isolated breast cancer stem cells from the total population of cancer cells using double-layered, soft agarose-based assay. This method demonstrates that cancer stem cells can survive and generate colony growth in an anchorage-independent culture model. The 0.005% crystal violet solution is used in this assay to visualize the generated colonies.
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| 3. |
- Rajendran, Vijayalakshmi, et al.
(author)
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Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents
- 2017
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In: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 64, s. 346-356
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Journal article (peer-reviewed)abstract
- Artificial corneas (keratoprostheses) and biosynthetic collagen-based corneal equivalents are surgical implants designed to ease the global burden of corneal blindness. However, keratoprostheses in many cases fail due to development of fibrous retro-corneal membranes (RCM). Fibrous membranes which develop in the anterior chamber after prosthesis implantation do so on a matrix of fibrin. This study investigated fibrin deposition and RCM formation after full-thickness collagen-based hydrogel implants and compared them with syngeneic and allogeneic corneal grafts in mice. Fibrin cleared from the anterior chamber within 14 days in both allo- and syn-grafts but, persisted in hydrogel implants and developed into dense retro-corneal membrane (RCM) which were heavily infiltrated by activated myofibroblasts. In contrast, the number of CD11 b(+) macrophages infiltrating the initial deposition of fibrin in the anterior chamber (AC) after hydrogel implantation was markedly reduced compared to syn- and allo-grafts. Inoculation of mesenchymal stem cells prior to collagen gel implant promoted clearance of gel associated fibrin from the anterior chamber. We propose that a failure of macrophage-mediated clearance of fibrin may be the cause of RCM formation after collagen-based hydrogel implants and that mesenchymal stem cell therapy promotes clearance of fibrin and prevents RCM formation. Statement of Significance The manuscript addresses the potential value of bone marrow-derived mesenchymal stem cell therapy for retro-corneal membrane (RCM) formation in full-thickness transplantation of biosynthetic corneal equivalents. This work reports the pathophysiological changes in the anterior chamber of the mouse eye following full-thickness recombinant human cross-linked collagen-based hydrogel implants in which persistent fibrin promotes the development of dense RCM. Furthermore, pre-treatment with mesenchymal stem cells reduces RCM formation and enhances corneal transparency. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 4. |
- Rajendran, Vijayalakshmi, et al.
(author)
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Stem cell aging and wound healing
- 2021
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In: Stem Cells and Aging. - 9780128200711 ; , s. 53-60
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Book chapter (peer-reviewed)abstract
- Aging is a natural process that promotes different pathologies and progressive functional losses of cells and tissues. Aging impacts stem cell reserve and function negatively, resulting in compromising tissue regeneration. Stem cell aging significantly impairs wound healing properties of different tissues due to the age-related aberrant changes like increased proinflammatory cytokines, accumulation of toxic metabolites, and senescence-associated molecules in the systemic milieu. The cascade of improper structural alterations leading to fibrosis is a serious concern in aged tissues upon injury due to the increased thickness/stiffness of extracellular matrix intermediated by matrix metalloproteinases. The aged-associated defects in the stem cell function can be revived by applying various exogenous interventions aiming at upregulating optimal reparative conditions for aged tissues. Thus, this chapter briefly covers the factors linked to impaired wound healing due to stem cell aging and enlists alternative treatment strategies to regulate tissue regeneration in aging.
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| 5. |
- Wickham, Abeni, et al.
(author)
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Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking
- 2015
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In: Advanced Functional Materials. - : Wiley: 12 months. - 1616-301X .- 1616-3028. ; 25:27, s. 4274-4281
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Journal article (peer-reviewed)abstract
- Noninvasive tracking of biomaterials is vital for determining the fate and degradation of an implant in vivo, and to show its role in tissue regeneration. Current biomaterials have no inherent capacity to enable tracing but require labeling with, for example, fluorescent dyes, or nanoparticles. Here a novel biocompatible fully conjugated electrospun scaffold is described, based on a semiconducting luminescent polymer that can be visualized in situ after implantation using fluorescence imaging. The polymer, poly [2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt -thiophene-2,5-diyl] (TQ1), is electrospun to form a fibrous mat. The fibers display fluorescence emission in the near-infrared region with lifetimes in the sub-nanosecond range, optimal for in situ imaging. The material shows no cytotoxic behaviors for embryonic chicken cardiomyocytes and mouse myoblasts, and cells migrate onto the TQ1 fibers even in the presence of a collagen substrate. Subcutaneous implantations of the material in rats show incorporation of the TQ1 fibers within the tissue, with limited inflammation and a preponderance of small capillaries around the fibers. The fluorescent properties of the TQ1 fibers are fully retained for up to 90 d following implantation and they can be clearly visualized in tissue using fluorescence and lifetime imaging, thus making it both a pro-angiogenic and traceable biomaterial.
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