Regenerative efficacy of mesenchymal stromal cells from human placenta in sensorineural hearing loss
Introduction
There are over 250 million patients worldwide suffering from incurable neurological disease, including deafness. Among patients suffering from deafness, almost 90% have some form of sensorineural dysfunction, such as sensory hair cell loss. It is estimated that the number of patients with neuron-related disease will double by the year 2030. Recently, the transplantation of stem cells has emerged as a promising therapeutic strategy for the treatment of permanent hearing loss [1], [2]. Furthermore, articles and broadcasts have reported that many incurable neurological diseases have been influenced by the use of in vivo therapeutic methods.
Mesenchymal stromal cells (MSCs) are stem cells with a capacity for self-renewal and can differentiate into mesoderm- and non-mesoderm-derived tissues. From a therapeutic perspective, MSCs are promising therapeutic agents for tissue regeneration due to their ease of preparation and immunologic privilege. Many other studies have isolated adult mesenchymal stromal cells from bone marrow, adipose tissue, umbilical cord blood (UCB), lung tissue, and Wharton's jelly [3], [4], [5], [6], [7]. Additionally, in our previous study, we demonstrated that UCB-derived mesenchymal stromal cells can differentiate into auditory hair cells and neuronal cells in vitro when exposed to a neuronal-developmental microenvironment. These cells can be differentiated into all three germ cell layers (neuron, supporting cells, and hair cells). Several studies have shown that mesenchymal stromal cells can be collected from placenta and umbilical cord blood as a derivative and used in the field of regenerative medicine [7], [8]. However, the amount of MSCs derived from UCB was very small, and it was difficult to achieve a proper environment for the differentiation of MSCs; consequently, they did not proliferate well. Recently, the isolation of MSCs from adult stromal cells has demonstrated that these cells are a potential source of mesenchymal stromal cells with therapeutic potential. Also, our previous studies and other articles have shown that many types of adult stem cells can differentiate into various cell types. In addition, these cells have been used in therapeutic pathways that promote wound-healing and effect incurable diseases and nerve disorders [7], [8], [9], [10], [11], [12], [13]. Consequently, the aim of this article was to evaluate the therapeutic regeneration and treatment effects with respect to hearing loss using mesenchymal stromal cells derived from human placenta. Also, it is mandatory to develop novel techniques for isolating, culturing, and mass producing MSCs with proliferative capacity.
Therefore, in this study, we have shown that human amniotic membrane-derived MSCs (AM-MSC) and chorionic membrane-derived MSCs (CM-MSC) can be differentiated into neurons, glial cells, and hair cells. In addition, we transplanted AM-MSC into an animal model of deafness and evaluated their therapeutic efficacy with respect to hearing.
Section snippets
Isolation of MSCs derived from human placenta
Placentas were collected after birth from women who carried to full-term after obtaining informed consent and were placed in heparin for storage. The average age of the pregnant women whose placentas were used in this study was 30–40 years. Placentas were isolated from a total of 13 women. These samples were washed three times with PBS and stored in serum-free α-MEM (Alpha Minimum Essential Medium, Gibco, Grand Island, NY). Samples were carefully divided into amnion membrane and chorionic
Isolation and differentiation of MSCs
After primary culture for 5 days, the culture dish contained mononuclear cells attached to the plate surface and in suspension. As the numbers of sub-cultures increased, the shapes of cells elongated and changed into those of fibroblast-like cells (Fig. 1A and D). All MSCs derived from amnion and chorion were maintained for at least 10 passages. Also, after each of the MSC samples was cultured in neurosphere differentiation medium containing bFGF and EGF, many sphere-forming floating cells were
Discussion
The placenta is an extra-embryonic organ with a rich source of progenitor or stem cells. The placenta has two sides; one is the fetal side consisting of amnion and chorion, and the other is the maternal side consisting of decidua [15], [16]. In this study, we demonstrated the proliferation, differentiation, and cellular restoration capacities of MSCs using amnion- and chorion-derived MSCs. MSCs isolated from the maternal side of human placenta represent an important cell type for stem cell
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The intravenous administration of skin-derived mesenchymal stem cells ameliorates hearing loss and preserves cochlear hair cells in cisplatin-injected mice: SMSCs ameliorate hearing loss and preserve outer hair cells in mice
2022, Hearing ResearchCitation Excerpt :BM-derived MSCs can be successfully transplanted into the cochlea of young mice but spontaneously differentiated into fibrocyte-like cells with Cx26 expression and did not affect the auditory function of mice. ( Kil et al., 2016) further demonstrated that placenta-derived MSCs could significantly improve hearing function in deaf animals, measured according to ABR and distortion-product otoacoustic emissions, and reported an increased number of SGNs in the cochlea and no apparent adverse effects or immunological rejection. Data from the neuropathological gene expression panel provide valuable insight into the effects of SMSCs on cisplatin-induced hearing loss in mice (Figs. 5 and 6).
2.48 - Stem Cell Approaches and Small Molecules
2020, The Senses: A Comprehensive Reference: Volume 1-7, Second EditionTransplantation of human limbus–derived mesenchymal stromal cells via occipital approach improves hearing in animal auditory neuropathy
2019, International Journal of Pediatric OtorhinolaryngologyCitation Excerpt :Liang et al. reported that HL-MSCs have neurotrophic functions and neuroprotective potential with reduced ischemic brain injury and improved functional recovery in rat models of focal cerebral ischemia [10]. The results were also compatible with previous reports that transplants of mesenchymal stromal cells derived from human placenta had regenerative efficacy in a deaf animal model of hearing loss [25]. In addition, neural-induced human MSCs from mastoid process marrow can promote cochlear cell regeneration in deaf guinea pigs [20].
Hearing Loss in the Elderly
2018, Clinics in Geriatric MedicineCitation Excerpt :Although some researchers have reported success with hair cell–like cells from mouse embryonic stem cells and induced pluripotent stem cells,67 others have focused on the development of the neural component of the inner ear system.68 Several studies have shown success with mesenchymal stem cells in regenerating cochlear spiral ganglion neurons and restoration of some improved auditory brainstem response and otoacoustic emission.69–71 Work with endogenous stem cells could bypass some challenges of exogenous stem cell use, with the best source for use in hearing restoration under investigation.72–76
Precision medicine in hearing loss
2018, Journal of Genetics and GenomicsCitation Excerpt :Further, the NGF administered with NSCs conferred transduction capacity protection and restored ABR threshold in mice with gentamicin ototoxicity induced HL (Han et al., 2017). In another study, mesenchymal stromal cells (MSCs) derived from human placenta were shown to improve ABR threshold value, distortion product otoacoustic emissions (DPOAE) level, and the number of SGNs in guinea pigs (Kil et al., 2016). Researchers have also proposed using amniotic fluid mesenchymal stem cells (hAFMSCs) to regenerate SGNs, due to the high pluripotency potentials, and restore IHC function (Mohammadian et al., 2017).
Stem cell therapy in sensorineural hearing loss: a systematic review
2023, Egyptian Journal of Otolaryngology
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Kicheol Kil & Mi Young Choi were co-first author & equally contributed to this article.