Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable

A 3-Dimensional-Printed Spine Localizer: Introducing the Concept of Online Dissemination of Novel Surgical Instruments

Background/Aims To date, applications of 3-dimensional (3D) printing in neurosurgery have been limited to the creation of anatomical models for training and simulation, fabrication of customized implants, and production of patient-specific surgical tool guides. We aim to demonstrate a new application of this technology for the online dissemination of novel surgical instrument designs across the world. Methods A link to a 3D printing file and instructions for assembly of a spine localizer are included in this article. This device was used to determine the optimal location of skin incision in lumbar microsurgery in 43 consecutive patients. Data regarding the accuracy of the surgeon's initial estimate of the target site based on palpation of anatomical landmarks and the accuracy of the localizer device in locating the target spine segment were prospectively collected. Results In 35 cases (81%), the surgeon’s initial estimate of the target site was correct. In the remaining 8 cases (19%), the initial estimate was off by 1 motion segment. Inaccuracy of the surgeon’s estimate was found to be associated with a higher body mass index and the presence of transitional lumbosacral anatomy, but not with age, sex, or location of the target segment. In all patients, the location of the incision guided by the localizer was found to overlie the target segment, yielding a device accuracy of 100%. There was no need to extend the incision or modify the surgical trajectory. Conclusion This 3D-printable localizer serves as an example of a device that can be disseminated online and printed at the point of use, thus promoting online tool-sharing by neurosurgeons

COMPARISON OF THE EFFECT OF SELF-CARE EDUCATION THROUGH HOSPITAL ROUTINE AND SOCIAL NETWORKS METHODS ON QUALITY OF LIFE OF CORONARY ARTERY BYPASS GRAFT PATIENTS

Background and Purpose: Coronary artery bypass grafting [CABG] is currently performed to relieve coronary artery disease. This study evaluates the effects of two self-care approaches of hospital routine technique and social networks on the quality of life of patients undergoing CABG. Methods: One hundred candidates of CABG were enrolled in this study who then completed the questionnaires of demographic characteristics and MacNew heart disease health-related quality of life. Before hospital discharge, patients attended a 20-30 min self-care education session, held by the researcher and received a selfcare booklet after CABG. Afterwards, participants were randomly divided into two groups of intervention and control. The intervention group received self-care education for four weeks after the surgery through a “Telegram Group”. Subjects of both study groups filled the questionnaires again after six weeks. Data analysis was performed with SPSS version 21 using descriptive and inferential statistics. Results: Both study groups were homogenous regarding demographic characteristics. According to the results of paired t-test, quality of life and its dimensions increased in both intervention and control groups after the intervention. On the other hand, results of independent t-test, used to compare the study groups, revealed lower quality of life in the intervention group before the test and no statistically significant difference between the groups after the test. Conclusion: Although the quality of life was at a lower level in the intervention group before the tests, the post intervention quality of life increased in this study group so that reached the mean quality of life of the control group. It seems that education in any form could improve the quality of life. Keywords: self-care education, approach, hospital routine, social networks, quality of life, coronary artery bypass gra