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100 Dinaki et al. | Journal of Clinical and Translational Research 2024; 10(2): 99-111
Table 1. Tissue engineering and regenerative medicine concepts
Stem cells Bioactive factors Scaffolds
Totipotent stem cells Pluripotent stem cells Multipotent stem cells Biological Synthetic
material material
Differentiate into Differentiate into the entire Differentiate into derivatives of Cytokines, growth Trachea Ceramic, metal,
embryonic and range of derivatives of multiple cell lineages factors, hormones, and and aortic polymer, and
extra-embryonic tissues all three embryonic germ morphogenic proteins allograft composite
layers
Obtained from an early Includes ESC and iPSC Includes NSCs and MSCs from the
embryo in the two-cell bone marrow, fat, skin, umbilical
stage cord, and/or muscle
Abbreviations: ESC: Embryonic stem cell; NSCs: Neural stem cells; MSCs: Mesenchymal stem cells; iPSC: induced pluripotent stem cell.

The field of otorhinolaryngology is extensive, including 4. Applications in Otology and Hearing
many different tissues and functions such as hearing, balance,
olfaction, facial expression, breathing, and speaking. The 4.1. Cochlea
diverse cells and tissues in the ear, nose, and throat, which Loss of hearing, congenital or acquired, results in the hair
are responsible for the related vital functions, contribute to cells’ inability to function correctly and subsequent death [9].
the heterogeneity challenging the exploitation of regenerative The absence of hair cells causes the death of spiral ganglion
therapies. This review aims to narratively summarize the neurons (SGNs) [9]. The mature mammalian cochlea in mammals
current state of tissue engineering and regenerative medicine in is incapable of hair cell regeneration [10]. Intracellular stem
otorhinolaryngology. cell activation and external stem cell transplantation are two
approaches in regenerative medicine that can potentially treat
2. Methods sensorineural hearing loss. The first approach is to stimulate the

This paper provides a literature overview of regenerative stem cells present in the organ of Corti, leading to the replacement
medicine and tissue engineering in otorhinolaryngology. of damaged hair cells. The second technique involves introducing
A literature search was conducted in PubMed, CINAHL, and stem cells from an external source into the inner ear. Several papers
Scopus using the following terms: “regenerative medicine,” reported using mesenchymal stem cells (MSCs) in animal models
“tissue engineering,” “regenerative surgery,” “stem cells,” “ear,” with hearing loss (Table 2). The injection of primary MSCs into
“cochlea,” “hearing loss,” “nose,” “larynx,” “head and neck,” the cochlea may result in the survival of hair cells [9]. However,
“vocal fold,” “trachea,” “craniofacial,” “otology,” “rhinology,” there is currently minimal indication of the transdifferentiation of
“laryngology,” “salivary glands,” and “otorhinolaryngology,” MSCs into hair-like cells or neurons in vivo [9].
from database inception to 2022. We used Boolean operators to Jang et al. implanted human bone marrow MSCs (BM-MSCs)
refine our search. In addition, review articles from the reference into the cochlea of neomycin-deafened guinea pigs, resulting in
list were included. a more significant number of SGNs as compared to the control
All randomized and non-randomized controlled prospective group [11]. MSCs have also been utilized in human research
and retrospective trials and case series of two or more patients but with minimal hearing enhancement [12]. In 2015, a clinical
experiment explored the efficacy of transplanting autologous
of any age were included. Only articles written in English were BM-MSCs in patients with sensorineural hearing loss. Two
further considered for the study. Duplicates were excluded. individuals were intravenously injected with cells, but their
Articles related to oral surgery and maxillofacial surgery were hearing did not improve [12]. Eleven children participated in
excluded. Although randomized controlled trials were prioritized another clinical trial using an autologous umbilical cord stem
and human clinical trials were preferred, animal trials were also cell infusion [13]. There were no adverse events reported, and
reviewed and included. Most articles were pre-clinical animal significant improvement in hearing was discovered from several
studies, reflecting the current state of research on this topic. hearing tests.
Information from completed early-phase clinical trials was It is more difficult to regenerate the auditory nerve using stem
included, while ongoing clinical trials were excluded. Articles cell technology due to the electrical features of those cells and
were analyzed and selected based on relevance to the topic of the requirement for an adequate connection with the remaining
interest. residual auditory neurons [14]. In vitro studies have revealed
3. Results that MSCs obtained from the olfactory mucosa can stimulate
the myelination of oligodendrocytes [9]. However, an ideal
The literature search identified 622 studies, of which 105 fit transplantation method has not been established thus far. Systemic
the eligibility criteria for data curation. Forty studies reported injection, injection into the scala tympani via the round window or
on otology and hearing, eight on craniofacial cartilaginous a basal turn cochleostomy, and injection into the scala media are
reconstruction, four on salivary glands, and 46 on laryngology. some of the stem cell transfer methods for the cochlea [14].
DOI: https://doi.org/10.36922/jctr.22.00151