Time filter

Source Type

Petah Tikva, Israel

Nambiar A.,Center for Stem Cell Research
Indian journal of medical ethics | Year: 2012

For consent in biomedical research, it is essential that research participants understand the need for research, the study protocol, the risk and benefits of participation, the freedom to participate or decline and the right to leave the study at any time. A structured questionnaire was used to assess understanding and knowledge among nursing trainees participating in a cohort study investigating exposure and latent tuberculosis at a tertiary care hospital. Data were collected for 138 participants. While 97% were aware of their enrollment into a research protocol, only 78% could state that it was a study on tuberculosis. Approximately two-thirds were aware of plans for blood collection, but not all of them knew the timings or number of samples. The majority (59%) participants had consulted others before making the decision to participate, and only 73% felt that their participation was completely voluntary. Even among healthcare trainees, emphasis needs to be placed on testing both the knowledge and understanding of participants to ensure the principle and practice of truly informed consent. Source

Balakrishnan B.,Christian Medical College | Jayandharan G.R.,Christian Medical College | Jayandharan G.R.,Center for Stem Cell Research
Current Gene Therapy | Year: 2014

Adeno-associated virus (AAV) based vectors have emerged as important tools for gene therapy in humans. The recent successes seen in Phase I/II clinical trials have also highlighted the issues related to the host and vector-related immune response that preclude the universal application of this promising vector system. A fundamental insight into the biological mechanisms by which AAV infects the host cell and a thorough understanding of the immediate and long-lived cellular responses to AAV infection is likely to offer clues and help design better intervention strategies to improve the therapeutic efficiency of AAV vectors. This article reviews the biology of AAV-host cellular interactions and outlines their application in the development of novel and improved AAV vector systems. © 2014 Bentham Science Publishers. Source

Selot R.S.,Center for Stem Cell Research | Hareendran S.,Center for Stem Cell Research | Jayandharan G.R.,Center for Stem Cell Research | Jayandharan G.R.,Christian Medical College
Current Pharmaceutical Biotechnology | Year: 2014

Gene therapy has become a clinical reality as demonstrated by remarkable benefits seen in Phase I/II clinical trials for hemophilia B, lipoprotein lipase deficiency and Leber's congenital amarousis. The choice of, and the improved understanding in vector characteristics have contributed significantly to this success. The adeno-associated virus (AAV) vectors used in these trials have been long known to be relatively safe and efficacious. However, certain factors, most notably host immunity to the vector, prevent their widespread use. In patients who have pre-existing antibodies to AAV, these vectors will be rapidly cleared. Administration of a relatively high initial dose of vector to achieve and sustain a higher margin of therapeutic benefit is limited by concerns of vector dose-dependent T cell response. Frequent vector administration necessitated by the non-integrating nature of the virus is difficult due to the variable, yet significant host immunological memory. Thus generation of AAV vectors that are immunologically inert is pivotal for the long-term success with this promising vector system. Several strategies, that aim targeted disruption of antigenic sites or those that chemically modify the vectors have been proposed for host immune evasion. While these approaches have been successful in the pre-clinical model systems, this continues to be a field of intense experimentation and constant improvisation due to limited information available on vector immunology or data from human studies. This review forms a comprehensive report on current strategies available to generate immunologically inert AAV vectors and their potential in mediating longterm gene transfer. © 2013 Bentham Science Publishers. Source

Sugimura R.,Stowers Institute for Medical Research | He X.C.,Stowers Institute for Medical Research | Venkatraman A.,Stowers Institute for Medical Research | Venkatraman A.,Center for Stem Cell Research | And 9 more authors.
Cell | Year: 2012

Wnt signaling is involved in self-renewal and maintenance of hematopoietic stem cells (HSCs); however, the particular role of noncanonical Wnt signaling in regulating HSCs in vivo is largely unknown. Here, we show Flamingo (Fmi) and Frizzled (Fz) 8, members of noncanonical Wnt signaling, both express in and functionally maintain quiescent long-term HSCs. Fmi regulates Fz8 distribution at the interface between HSCs and N-cadherin+ osteoblasts (N-cad +OBs that enrich osteoprogenitors) in the niche. We further found that N-cad+OBs predominantly express noncanonical Wnt ligands and inhibitors of canonical Wnt signaling under homeostasis. Under stress, noncanonical Wnt signaling is attenuated and canonical Wnt signaling is enhanced in activation of HSCs. Mechanistically, noncanonical Wnt signaling mediated by Fz8 suppresses the Ca2+-NFAT- IFNγ pathway, directly or indirectly through the CDC42-CK1α complex and also antagonizes canonical Wnt signaling in HSCs. Taken together, our findings demonstrate that noncanonical Wnt signaling maintains quiescent long-term HSCs through Fmi and Fz8 interaction in the niche. © 2012 Elsevier Inc. Source

Mizrahi K.,Center for Stem Cell Research | Askenasy N.,Center for Stem Cell Research
Blood | Year: 2014

Secretion of ligands of the tumor necrosis factor (TNF) superfamily is a conserved response of parenchymal tissues to injury and inflammation that commonly perpetuates elimination of dysfunctional cellular components by apoptosis. The same signals of tissue injury that induce apoptosis in somatic cells activate stem cells and initiate the process of tissue regeneration as a coupling mechanism of injury and recovery. Hematopoietic stem and progenitor cells upregulate the TNF family receptors under stress conditions and are transduced with trophic signals. The progeny gradually acquires sensitivity to receptor-mediated apoptosis along the differentiation process, which becomes the major mechanism of negative regulation of mature proliferating hematopoietic lineages and immune homeostasis. Receptor/ligand interactions of the TNF family are physiological mechanisms transducing the need for repair, which may be harnessed in pathological conditions and transplantation. Because these interactions are physiological mechanisms of injury, neutralization of these pathways has to be carefully considered in disorders that do not involve intrinsic aberrations of excessive susceptibility to apoptosis. © 2014 by The American Society of Hematology. Source

Discover hidden collaborations