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.

Mesenchymal stem cells (MSCs) can be isolated from different tissue origins, such as the bone marrow, the placenta, the umbilical cord, adipose tissues, and skin tissues. MSCs can secrete anti-inflammatory molecules and growth factors for tissue repair and remodeling. However, the ability of skin-derived MSCs (SMSCs) to repair cochlear damage and ameliorate hearing loss remains unclear. Cisplatin is a commonly used chemotherapeutic agent that has the side effect of ototoxicity due to inflammation and oxidative stress. This study investigated the effects of SMSCs on cisplatin-induced hearing loss in mice. Two independent experiments were designed for modeling cisplatin-induced hearing loss in mice, one for chronic toxicity (4 mg/kg intraperitoneal [IP] injection once per day for 5 consecutive days) and the other for acute toxicity (25 mg/kg IP injection once on day one). Three days after cisplatin injection, 1 × 10 ⁶ or 3 × 10 ⁶ SMSCs were injected through the tail vein. Data on auditory brain responses suggested that SMSCs could significantly reduce the hearing threshold of cisplatin-injected mice. Furthermore, immunohistochemical staining data suggested that SMSCs could significantly ameliorate the loss of cochlear hair cells, TUNEL-positive cells and cleaved caspase 3-positive cells in cisplatin-injected mice. Neuropathological gene analyses revealed that SMSCs treatment could downregulate the expression of cochlear genes involved in apoptosis, autophagy, chromatin modification, disease association, matrix remodeling, oxidative stress, tissue integrity, transcription, and splicing and unfolded protein responses. Additionally, SMSCs treatment could upregulate the expression of cochlear genes affecting the axon and dendrite structures, cytokines, trophic factors, the neuronal skeleton and those involved in carbohydrate metabolism, growth factor signaling, myelination, neural connectivity, neural transmitter release, neural transmitter response and reuptake, neural transmitter synthesis and storage, and vesicle trafficking. Results from TUNEL and caspase 3 staining further confirmed that cisplatin-induced apoptosis in cochlear tissues of cisplatin-injected mice could be reduced by SMSCs treatment. In conclusion, the evidence of the effects of SMSCs in favor of ameliorating ototoxicity-induced hearing loss suggests a potential clinical application.
Competing Interests: Declaration of Competing Interest Maria Von Med-Biotechnology Co., Ltd, Taiwan provided a partial grant. The authors independently characterized the SMSCs and evaluated the effects of SMSCs in cisplatin-induced hearing loss. Stella Chin-Shaw Tsai has no relation with Maria Von Med- Biotechnology Co., Ltd. Frank Cheau-Feng Lin has no relation with Maria Von Med- Biotechnology Co., Ltd. Kuang-Hsi Chang has no relation with Maria Von Med- Biotechnology Co., Ltd. Min-Chih Li has no relation with Maria Von Med- Biotechnology Co., Ltd. Ruey-Hwang Chou has no relation with Maria Von Med- Biotechnology Co., Ltd. Mei-Yue Huang is the founder of Maria Von Med- Biotechnology Co., Ltd. Yen-Chung Chen was the chief technology officer in Maria Von Med- Biotechnology Co., Ltd. Chien-Yu Kao has no relation with Maria Von Med- Biotechnology Co., Ltd. Ching-Chang Cheng has no relation with Maria Von Med- Biotechnology Co., Ltd. Hung-Ching Lin has no relation with Maria Von Med- Biotechnology Co., Ltd. Yi-Chao Hsu has no relation with Maria Von Med- Biotechnology Co., Ltd.
(Copyright © 2021 Elsevier B.V. All rights reserved.)