Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation

Peterson, Julia; Lin, Brian M.; Barrios-Camacho, Camila M.; Herrick, Daniel B.; Holbrook, Eric H.; Jang, Wooseung; Coleman, Julie H.; Schwob, James E.

doi:10.1016/j.stemcr.2019.02.014

Cited by 37 publications

(42 citation statements)

References 53 publications

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“…They may also contribute to virus spread to the olfactory bulb vascular pericytes. Magnetic resonance imaging (MRI) studies of the olfactory bulb [ 33 , 34 ], in which ACE2 are only expressed in vascular pericytes but not in neurons, may show inflammatory signs suggesting that the infection process can extend more centrally and promote inflammatory response [ 35 ]. Inflammatory causes are often quickly reversible for example after a one-week trial of high dose of corticosteroids or simply days after the resolution of the viral infection suggesting that the olfactory neurons and bulbs are still somewhat intact.…”

Section: Discussionmentioning

confidence: 99%

ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review

Lechien

Radulesco

Calvo‐Henríquez³

et al. 2020

Head and Neck Pathol

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To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. The following outcomes were considered: sample origin (animal versus human); detection method; anatomical location and cell types. PRISMA checklist and modified population, intervention, comparison, outcome, timing and setting (PICOTS) framework were used to perform the review. Of the 24 identified studies, 17 met our inclusion criteria. Thirteen studies were conducted during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells. TMPRSS2 was found in goblet and apical respiratory cells. ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. Animal studies suggested that ACE2 expression may vary regarding age. There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.

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Section: Discussionmentioning

confidence: 99%

ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review

Lechien

Radulesco

Calvo‐Henríquez³

et al. 2020

Head and Neck Pathol

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“…The first session focused on stem cells in sensory organs for smell, taste, vision, and balance; the roles of stem cells in normal tissue development and regeneration; and the potential uses of stem cells in modeling complex sensory tissues or in disease therapies (e.g., Ren et al 2014 ; Vergara et al 2017 ; Gaillard et al 2019 ; Kurtenbach et al 2019 ; Peterson et al 2019 ; Sayyid et al, 2019 ).…”

Section: Chemosensory Disordersmentioning

confidence: 99%

“…Progress has also been made in the primary culture of human olfactory stem cells and their differentiation into olfactory sensory neurons, for example, culture expansion of de-differentiated murine basal cells ( Goldstein et al 2016 ). These olfactory stem cells are being transplanted into model hosts (e.g., mice and rats) to test their ability to recolonize olfactory tissues ( Peterson et al 2019 ). A primary cell culture approach can be used to identify signaling pathways, molecular targets, and compounds that force olfactory stem cell activation and neurogenesis and, thereby, exploit the endogenous capacity of the resident stem cells of the olfactory epithelium.…”

Section: Suggestions For High-yield Next Stepsmentioning

confidence: 99%

Identifying Treatments for Taste and Smell Disorders: Gaps and Opportunities

et al. 2020

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The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the daily enjoyment of food, friends and family, and our surroundings. Over 12% of the US population is estimated to experience taste and smell (chemosensory) dysfunction. Yet, despite this high prevalence, long-term, effective treatments for these disorders have been largely elusive. Clinical successes in other sensory systems, including hearing and vision, have led to new hope for developments in the treatment of chemosensory disorders. To accelerate cures, we convened the “Identifying Treatments for Taste and Smell Disorders” conference, bringing together basic and translational sensory scientists, health care professionals, and patients to identify gaps in our current understanding of chemosensory dysfunction and next steps in a broad-based research strategy. Their suggestions for high-yield next steps were focused in 3 areas: increasing awareness and research capacity (e.g., patient advocacy), developing and enhancing clinical measures of taste and smell, and supporting new avenues of research into cellular and therapeutic approaches (e.g., developing human chemosensory cell lines, stem cells, and gene therapy approaches). These long-term strategies led to specific suggestions for immediate research priorities that focus on expanding our understanding of specific responses of chemosensory cells and developing valuable assays to identify and document cell development, regeneration, and function. Addressing these high-priority areas should accelerate the development of novel and effective treatments for taste and smell disorders.

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“…Olfactory stem cells have been established in vitro as cloned neurospheres from rat 18 , mouse 19 and human 20 . Promisingly, these cells are optimal candidates to the source of cell transplantation in tissue repairs including facial nerve regeneration 21 , restoration of normal substantia nigra structure 22 , improvement of stroke-mediated neurological dysfunction 23 , restoration of motor functions in spinal cord injury model 24 , recovery of neuroplasticity in hippocampal lesions 25 and preservation of auditory function during early-onset progressive hearing loss 26 .…”

Section: Introductionmentioning

confidence: 99%

Expansion of murine and human olfactory epithelium/mucosa colonies and generation of mature olfactory sensory neurons under chemically defined conditions

Ren¹,

Wang²,

Zhang³

et al. 2021

Theranostics

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Olfactory dysfunctions, including hyposmia and anosmia, affect ~100 million people around the world and the underlying causes are not fully understood. Degeneration of olfactory sensory neurons and incapacity of globose basal cells to generate olfactory sensory neurons are found in elder people and patients with smell disorders. Thus, olfactory stem cell may function as a promising tool to replace inactivated globose basal cells and to generate sensory neurons. Methods: We established clonal expansion of cells from the murine olfactory epithelium as well as colony growth from human olfactory mucosa using Matrigel-based three-dimensional system. These colonies were characterized by immunostaining against olfactory epithelium cellular markers and by calcium imaging of responses to odors. Chemical addition was optimized to promote Lgr5 expression, colony growth and sensory neuron generation, tested by quantitative PCR and immunostaining against progenitor and neuronal markers. The differential transcriptomes in multiple signaling pathways between colonies under different base media and chemical cocktails were determined by RNA-Seq. Results: In defined culture media, we found that VPA and CHIR99021 induced the highest Lgr5 expression level, while LY411575 resulted in the most abundant yield of OMP + mature sensory neurons in murine colonies. Different base culture media with drug cocktails led to apparent morphological alteration from filled to cystic appearance, accompanied with massive transcriptional changes in multiple signaling pathways. Generation of sensory neurons in human colonies was affected through TGF-β signaling, while Lgr5 expression and cell proliferation was regulated by VPA. Conclusion: Our findings suggest that targeting expansion of olfactory epithelium/mucosa colonies in vitro potentially results in discovery of new source to cell replacement-based therapy against smell loss.

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Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation

Cited by 37 publications

References 53 publications

ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review

ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review

Identifying Treatments for Taste and Smell Disorders: Gaps and Opportunities

Expansion of murine and human olfactory epithelium/mucosa colonies and generation of mature olfactory sensory neurons under chemically defined conditions

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