Author
Bharti Bisht
Bio: Bharti Bisht is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Cellular differentiation & Stem cell. The author has an hindex of 7, co-authored 13 publications receiving 442 citations.
Papers
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TL;DR: It is shown in mouse and human airway basal stem cells (ABSCs) that intracellular flux from low to moderate ROS levels is required for stem cell self-renewal and proliferation and redox-mediated regulation of lung stem cell function.
228 citations
TL;DR: It is demonstrated that airway submucosal gland (SMG) duct cells, in addition to BCs, survived severe hypoxic‐ischemic injury and are therefore a multipotent stem cell for airway epithelial repair.
Abstract: The airway epithelium is in direct contact with the environment and therefore constantly at risk for injury. Basal cells (BCs) have been found to repair the surface epithelium (SE), but the contribution of other stem cell populations to airway epithelial repair has not been identified. We demonstrated that airway submucosal gland (SMG) duct cells, in addition to BCs, survived severe hypoxic-ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self-renewal and differentiation potential of duct cells and BCs. We found that only duct cells were capable of regenerating SMG tubules and ducts, as well as the SE overlying the SMGs. SMG duct cells are therefore a multipotent stem cell for airway epithelial repair This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell-based therapies for patients with airway diseases.
128 citations
TL;DR: It is found that only aldehyde dehydrogenase (ALDH)hi basal and duct cells were capable of sphere formation, and global inhibition of ALDH, as well as specific inhibition of the ALDH2 isoform, inhibited self‐renewal of both basal andduct cells, thereby producing fewer and smaller spheres.
Abstract: Basal cells and submucosal gland (SMG) duct cells have been isolated and shown to be stem/progenitor cell populations for the murine airway epithelium. However, methods for the isolation of basal and SMG duct cells from human airways have not been defined. We used an optimized two-step enzyme digestion protocol to strip the surface epithelium from tracheal specimens separate from SMG cells, and we then sorted the basal and duct stem/progenitors using fluorescence-activated cell sorting. We used nerve growth factor receptor, as well as a combination of CD166 and CD44, to sort basal cells and also used CD166 to isolate SMG duct cells. Sorted stem/progenitor cells were cultured to characterize their self-renewal and differentiation ability. Both basal and SMG duct cells grew into spheres. Immunostaining of the spheres showed mostly dense spheres with little to no central lumen. The spheres expressed cytokeratins 5 and 14, with some mucus- and serous-secreting cells. The sphere-forming efficiency and the rate of growth of the spheres varied widely between patient samples and correlated with the degree of hyperplasia of the epithelium. We found that only aldehyde dehydrogenase (ALDH)(hi) basal and duct cells were capable of sphere formation. Global inhibition of ALDH, as well as specific inhibition of the ALDH2 isoform, inhibited self-renewal of both basal and duct cells, thereby producing fewer and smaller spheres. In conclusion, we have developed methods to isolate basal and SMG duct cells from the surface epithelium and SMGs of human tracheas and have developed an in vitro model to characterize their self-renewal and differentiation.
87 citations
TL;DR: It is found that Wnt/β-catenin within ABSCs was essential for proliferation post-injury in vivo, and multiple spatiotemporally dynamic Wnt-secreting niches that regulate functionally distinct phases of airway regeneration and aging are underscore.
36 citations
TL;DR: In this article, the authors summarize the advances in scaffold fabrication techniques, emphasizing 3D printing of biomimetic bone grafts, which will be used to replace traditional bone graft substitutes such as metals, biomaterial coated metals and biodegradable scaffolds.
Abstract: The need for bone grafts is tremendous, and that leads to the use of autograft, allograft, and bone graft substitutes. The biology of the bone is quite complex regarding cellular composition and architecture, hence developing a mineralized connective tissue graft is challenging. Traditionally used bone graft substitutes including metals, biomaterial coated metals and biodegradable scaffolds, suffer from persistent limitations. With the advent and rise of additive manufacturing technologies, the future of repairing bone trauma and defects seems to be optimistic. 3D printing has significant advantages, the foremost of all being faster manipulation of various biocompatible materials and live cells or tissues into the complex natural geometries necessary to mimic and stimulate cellular bone growth. The advent of new-generation bioprinters working with high-precision, micro-dispensing and direct digital manufacturing is aiding in ground-breaking organ and tissue printing, including the bone. The future bone replacement for patients holds excellent promise as scientists are moving closer to the generation of better 3D printed bio-bone grafts that will be safer and more effective. This review aims to summarize the advances in scaffold fabrication techniques, emphasizing 3D printing of biomimetic bone grafts.
33 citations
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TL;DR: An impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients for non-small-cell lung cancers, including immunotherapy.
Abstract: Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to have diverse pathological features. During the past decade, in-depth analyses of lung cancer genomes and signalling pathways have further defined NSCLCs as a group of distinct diseases with genetic and cellular heterogeneity. Consequently, an impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients. Many targeted therapies have been developed with compelling clinical proofs of concept; however, treatment responses are typically short-lived. Further studies of the tumour microenvironment have uncovered new possible avenues to control this deadly disease, including immunotherapy.
1,189 citations
TL;DR: The different modes of regulation of Nrf2 activity are reviewed and the current knowledge of NRF2-mediated transcriptional control is reviewed to provide insight into mechanisms of disease and instruct new treatment strategies.
Abstract: Significance: Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that coordinates the basal and stress-inducible activation of a vast array of cytoprotective genes. Unders...
1,114 citations
Duke University1, Durham University2, University of California, San Francisco3, University of Pennsylvania4, University of Texas Southwestern Medical Center5, Yale University6, University of North Carolina at Chapel Hill7, Cedars-Sinai Medical Center8, University of Michigan9, University of Cincinnati Academic Health Center10
TL;DR: The multiple stem/progenitor populations in different regions of the adult lung, the plasticity of their behavior in injury models, and molecular pathways that support homeostasis and repair are highlighted.
716 citations
TL;DR: Nrf2 activity is tightly controlled via CRLKeap1 and SCFβ-TrCP by oxidative stress and energy-based signals, allowing it to mediate adaptive responses that restore redox homeostasis and modulate intermediary metabolism.
622 citations
TL;DR: ADCs can be modelled by KrasG12D expression (long latency), KrasD expression and Trp53-null, and epidermal growth factor receptor (EGFR)T790M/L858R, among other genetic models, and they are thought to arise from more distal airway cells.
Abstract: Nature Reviews Cancer 14, 535–546 (2014) In the original version of this article, the word 'proximal' was incorrectly used twice instead of 'distal' in two sentences in the legend for Figure 2. The sentences should have stated “ADCs can be modelled by KrasG12D expression (long latency), KrasG12D expression and Trp53-null, and epidermal growth factor receptor (EGFR)T790M/L858R, among other genetic models, and they are thought to arise from more distal airway cells.
491 citations