LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea

Sensorineural hearing loss is mainly caused by irreversible damage to sensory hair cells (HCs). A subgroup of supporting cells (SCs) in the cochlea express leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker for tissue-resident stem cells. LGR5+ SCs could be used as an endogenous source of stem cells for regeneration of HCs to treat hearing loss. Here, we report long-term presence of LGR5+ SCs in the mature adult cochlea and survival of LGR5+ SCs after severe ototoxic trauma characterized by partial loss of inner HCs and complete loss of outer HCs. Surviving LGR5+ SCs (confirmed by GFP expression) were located in the third row of Deiters’ cells. We observed a change in the intracellular localization of GFP, from the nucleus in normal-hearing to cytoplasm and membrane in deafened mice. These data suggests that the adult mammalian cochlea possesses properties essential for regeneration even after severe ototoxic trauma.

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Stem Cell Differentiation Stage Factors (SCDSFs) Taken from Zebrafish Embryo During Organogenesis and Their Role as Epigenetics Regulators Able to Reverse Neurosensory Hearing Loss

10.20944/preprints202111.0502.v1 ◽

2021 ◽

Author(s):

Pier Mario Biava ◽

Stefano Ciaurelli ◽

Riccardo Benzi Cibelli ◽

Gianpaolo Pisano

Keyword(s):

Stem Cells ◽

Hearing Loss ◽

Stem Cell ◽

Middle Ear ◽

Zebrafish Embryo ◽

Stem Cell Differentiation ◽

Speech Development ◽

Mechanical Transmission ◽

Cell Degeneration ◽

Irreversible Damage

Hearing dysfunctions can be classified by type, degree, configuration, time of onset, aetiology, and finally, consequences on speech development. They can be divided into conductive, mixed, central types and sensorineural. Conductive hearing loss (CHL) results from interference with the mechanical transmission of sound through the external and middle ear; it can be congenital, as a consequence of anatomic abnormalities, but it can commonly be acquired following middle ear inflammatory pathologies. Sensorineural hearing loss (SNHL) results from failure to transduce vibrations to neural impulses in the cochlean and is a consequence of an irreversible damage to the differentiated cells which make up the organ of hearing and the acoustic paths at various levels. Mixed hearing loss involves a combination of these two types in the same ear. Studies in neuroscience field have shown that the prevention of cell degeneration is only possible if all the factors taken at the different stages of stem cells’ multiplication and differentiation are administered together. We have demonstrated this in a recent study on the ability of SCDSFs to prevent neurodegeneration in hippocampal cells of the CA1 zone in mice. This study confirms previous findings demonstrating that early developmental zebrafish embryo extracts could act as a modulator of senescence in human mesenchymal stem cells (hMSC) isolated from many adult tissues. These findings have open a promising way for the approaches promoting the rejuvenation and regeneration of different tissues, by-passing stem cell transplantation. In the present clinical trial we have used SCDSFs to study the possible reversion of neurosensory hearing loss, until now considered an irreversible condition.

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Regeneration of sensory hair cells after acoustic trauma

Science ◽

10.1126/science.3381100 ◽

1988 ◽

Vol 240 (4860) ◽

pp. 1772-1774 ◽

Cited By ~ 530

Author(s):

JT Corwin ◽

DA Cotanche

Keyword(s):

Hearing Loss ◽

Hair Cells ◽

Acoustic Trauma ◽

Sensory Cells ◽

Lesion Site ◽

Supporting Cells ◽

Profound Hearing Loss ◽

Cochlear Hair Cells ◽

Sensory Hair ◽

Sensory Hair Cells

Any loss of cochlear hair cells has been presumed to result in a permanent hearing deficit because the production of these cells normally ceases before birth. However, after acoustic trauma, injured sensory cells in the mature cochlea of the chicken are replaced. New cells appear to be produced by mitosis of supporting cells that survive at the lesion site and do not divide in the absence of trauma. This trauma-induced division of normally postmitotic cells may lead to recovery from profound hearing loss.

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An Update on Mesenchymal Stem Cell-Centered Therapies in Temporomandibular Joint Osteoarthritis

Stem Cells International ◽

10.1155/2021/6619527 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Yifan Zhao ◽

Liang Xie

Keyword(s):

Stem Cells ◽

Temporomandibular Joint ◽

Stromal Vascular Fraction ◽

Cartilage Degeneration ◽

Therapeutic Effects ◽

Cellular Therapies ◽

Temporomandibular Joint Osteoarthritis ◽

Multipotent Progenitor Cells ◽

Resident Stem Cells

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by cartilage degeneration, disrupted subchondral bone remodeling, and synovitis, seriously affecting the quality of life of patients with chronic pain and functional disabilities. Current treatments for TMJOA are mainly symptomatic therapies without reliable long-term efficacy, due to the limited self-renewal capability of the condyle and the poorly elucidated pathogenesis of TMJOA. Recently, there has been increased interest in cellular therapies for osteoarthritis and TMJ regeneration. Mesenchymal stem cells (MSCs), self-renewing and multipotent progenitor cells, play a promising role in TMJOA treatment. Derived from a variety of tissues, MSCs exert therapeutic effects through diverse mechanisms, including chondrogenic differentiation; fibrocartilage regeneration; and trophic, immunomodulatory, and anti-inflammatory effects. Here, we provide an overview of the therapeutic roles of various tissue-specific MSCs in osteoarthritic TMJ or TMJ regenerative tissue engineering, with an additional focus on joint-resident stem cells and other cellular therapies, such as exosomes and adipose-derived stromal vascular fraction (SVF). Additionally, we summarized the updated pathogenesis of TMJOA to provide a better understanding of the pathological mechanisms of cellular therapies. Although limitations exist, MSC-centered therapies still provide novel, innovative approaches for TMJOA treatment.

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An adult uterine hemangioblast: evidence for extramedullary self-renewal and clonal bilineage potential

Blood ◽

10.1182/blood-2010-01-266882 ◽

2010 ◽

Vol 116 (16) ◽

pp. 2932-2941 ◽

Cited By ~ 13

Author(s):

Zhuo Sun ◽

Yuemei Zhang ◽

Keith R. Brunt ◽

Jun Wu ◽

Shu-Hong Li ◽

...

Keyword(s):

Stem Cells ◽

Cell Fate ◽

Cell Renewal ◽

Self Renewal ◽

Stem Cell Maintenance ◽

Resident Stem Cells ◽

Multipotent Differentiation

Abstract Stem cells exhibit long-term self-renewal by asymmetric division and multipotent differentiation. During embryonic development, cell fate is determined with predictable orientation, differentiation, and partitioning to form the organism. This includes the formation of a hemangioblast from which 2 derivative cell clusters commit to either a hematopoietic or an endothelial lineage. Frequently, it is not clear whether tissue resident stem cells in the adult originate from the bone marrow. Here, we show that blast colony-forming cells exhibiting bilineage (hematopoietic and vascular) potential and long-term self-renewal originate from the uterus in the mouse. This is the first in vitro and in vivo evidence of an adult hemangioblast retained from development in the uterus. Our findings offer new understanding of uterine cell renewal and turnover and may provide insights and opportunities for the study of stem cell maintenance.

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Caspases and apoptosis

Essays in Biochemistry ◽

10.1042/bse0380009 ◽

2002 ◽

Vol 38 ◽

pp. 9-19 ◽

Cited By ~ 121

Author(s):

Guy S Salvesen

Keyword(s):

Cysteine Proteases ◽

Signalling Pathways ◽

Term Survival ◽

Mature Adult ◽

Intracellular Signalling Pathways ◽

Adult Cell ◽

Caspase Family ◽

Cell Fragments ◽

Pro Inflammatory Cytokines

The ability of metazoan cells to undergo programmed cell death is vital to both the precise development and long-term survival of the mature adult. Cell deaths that result from engagement of this programme end in apoptosis, the ordered dismantling of the cell that results in its 'silent' demise, in which packaged cell fragments are removed by phagocytosis. This co-ordinated demise is mediated by members of a family of cysteine proteases known as caspases, whose activation follows characteristic apoptotic stimuli, and whose substrates include many proteins, the limited cleavage of which causes the characteristic morphology of apoptosis. In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.

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