Inner Ear Progenitor Cells can be Generated
            <i>in Vitro</i>
            from Human Bone Marrow Mesenchymal Stem Cells

Boddy, Sarah; Chen, Wei; Romero-Guevara, Ricardo; Kottam, Lucksy; Bellantuono, Ilaria; Rivolta, Marcelo N.

doi:10.2217/rme.12.58

Cited by 29 publications

(20 citation statements)

References 38 publications

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“…A number of recent studies have shown that pluripotent stem cells can be differentiated into progenitor and HC‐like cells under different adherent culture conditions. However, the methods applied to these studies have relied upon co‐culturing cells with tissues from the developing inner ear (Boddy et al ., ; White et al ., ), the chicken utricle (Oshima et al ., ) or using conditioned medium that contained stromal factors (Ouji et al ., ). For these reasons, it is questionable whether these experiments are suitable for assessing the grafting capacity of the inner ear progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

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Culture conditions have an impact on the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells

Abboud

Fontbonne

Watabe

et al. 2016

J Tissue Eng Regen Med

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The generation of replacement inner ear hair cells (HCs) remains a challenge and stem cell therapy holds the potential for developing therapeutic solutions to hearing and balance disorders. Recent developments have made significant strides in producing mouse otic progenitors using cell culture techniques to initiate HC differentiation. However, no consensus has been reached as to efficiency and therefore current methods remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors from embryonic stem (ES) cells in two cell culture systems: suspension vs. adherent conditions. In the present study, an ES cell line derived from an Atoh1-green fluorescent protein (GFP) transgenic mouse was used to track the generation of otic progenitors, initial HCs and to compare these two differentiation systems. We used a two-step short-term differentiation method involving an induction period of 5 days during which ES cells were cultured in the presence of Wnt/transforming growth factor TGF-β inhibitors and insulin-like growth factor IGF-1 to suppress mesoderm and reinforce presumptive ectoderm and otic lineages. The generated embryoid bodies were then differentiated in medium containing basic fibroblast growth factor (bFGF) for an additional 5 days using either suspension or adherent culture methods. Upon completion of differentiation, quantitative polymerase chain reaction analysis and immunostaining monitored the expression of otic/HC progenitor lineage markers. The results indicate that cells differentiated in suspension cultures produced cells expressing otic progenitor/HC markers at a higher efficiency compared with the production of these cell types within adherent cultures. Furthermore, we demonstrated that a fraction of these cells can incorporate into ototoxin-injured mouse postnatal cochlea explants and express MYO7A after transplantation. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

“…Recent advances in the understanding of molecular mechanisms related to HC production and stem cell technology have raised the possibility that HC‐like cells might be generated from both embryonic and adult stem cell sources (Savary et al ., ; Oshima et al ., ; Boddy et al ., ; Ouji et al ., ; Koehler et al ., ; Ronaghi et al ., ).…”

Section: Introductionmentioning

confidence: 98%

Culture conditions have an impact on the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells

Abboud

Fontbonne

Watabe

et al. 2016

J Tissue Eng Regen Med

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“…Nevertheless, otic progenitors can be induced from pluripotent stem cells by activating FGF signaling with ligands involved in the generation of the placode in vivo , such as FGF3 and FGF10 (Chen et al, ). Alternatively, inner ear progenitors can be generated in vitro , from other stem cell populations, circumventing the above‐described procedure of stepwise addition of signaling molecules (Boddy et al, ). Human mesenchymal stem cells were cultured in media which previously has been used to culture human fetal auditory cells.…”

Section: Focussing On the Inner Earmentioning

confidence: 99%

Building an Artificial Stem Cell Niche: Prerequisites for Future 3D‐Formation of Inner Ear Structures—Toward 3D Inner Ear Biotechnology

Groot

Sliedregt

Benthem

et al. 2019

The Anatomical Record

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In recent years, there has been an increased interest in stem cells for the purpose of regenerative medicine to deliver a wide range of therapies to treat many diseases. However, two‐dimensional cultures of stem cells are of limited use when studying the mechanism of pathogenesis of diseases and the feasibility of a treatment. Therefore, research is focusing on the strengths of stem cells in the three‐dimensional (3D) structures mimicking organs, that is, organoids, or organ‐on‐chip, for modeling human biology and disease. As 3D technology advances, it is necessary to know which signals stem cells need to multiply and differentiate into complex structures. This holds especially true for the complex 3D structure of the inner ear. Recent work suggests that although other factors play a role, the extracellular matrix (ECM), including its topography, is crucial to mimic a stem cell niche in vitro and to drive stem cells toward the formation of the tissue of interest. Technological developments have led to the investigation of biomaterials that closely resemble the native ECM. In the fast forward moving research of organoids and organs‐on‐chip, the inner ear has hardly received attention. This review aims to provide an overview, by describing the general context in which cells, matrix and morphogens cooperate in order to build a tissue, to facilitate research in 3D inner ear technology. Anat Rec, 303:408–426, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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“…Other authors maintain that putative cochlear SCs may derive from the mesenchymal SCs (MSCs) reservoir located in the inner ear stroma underlying the epithelial tissue [41]. Although it remains unclear, some studies have shown that MSCs are able to differentiate in vitro in both HClike cells and neurons [42,43].…”

Section: Cochlear Scsmentioning

confidence: 99%

Regenerative medicine in hearing recovery

Simoni

Orsini²,

Chicca

et al. 2017

Cytotherapy

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Hearing loss, or deafness, affects 360 million people worldwide of which about 32 million are children. Deafness is irreversible when it involves sensory hair cell death because the regenerative ability of these cells is lost in mammals after embryo development. The therapeutic strategies for deafness include hearing aids and/or implantable devices. However, not all patients are eligible or truly benefit from these medical devices. Regenerative medicine based on stem cell application could play a role in both improvement of extant medical devices and in vivo recovery of auditory function by regeneration of inner ear cells and neurons. A review of recent literature on the subject indicates that two promising approaches to renewal and differentiation of cochlear tissues are transplantation of stem cells and in situ administration of growth factors. Rather than directly regenerating dead cells, these procedures apparently induce, through various pathways, differentiation of resident cochlear cells. More studies on the possible adverse effects of transplanted cells and the recovery of tonotopic sensorineural activity or required. To date, no reliable clinical results have been obtained in the field of cochlear regeneration.

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Inner Ear Progenitor Cells can be Generated in Vitro from Human Bone Marrow Mesenchymal Stem Cells

Abstract: This study demonstrates that hMSCs can be driven to express key genes found in the otic lineages and thereby promotes their status as candidates for regenerative therapies for deafness.

Cited by 29 publications

References 38 publications

Culture conditions have an impact on the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells

Culture conditions have an impact on the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells

Building an Artificial Stem Cell Niche: Prerequisites for Future 3D‐Formation of Inner Ear Structures—Toward 3D Inner Ear Biotechnology

Regenerative medicine in hearing recovery

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