IGF-1 介导嗅鞘干细胞对听觉毛细胞的神经保护作用。

IGF-1 Mediated Neuroprotective Effects of Olfactory-Derived Mesenchymal Stem Cells on Auditory Hair Cells.

机构信息

BC Rotary Hearing and Balance Centre at St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, BC, Canada.

出版信息

J Otolaryngol Head Neck Surg. 2024 Jan-Dec;53:19160216241258431. doi: 10.1177/19160216241258431.

Abstract

IMPORTANCE

Mesenchymal stem cells (MSCs) have the capability of providing ongoing paracrine support to degenerating tissues. Since MSCs can be extracted from a broad range of tissues, their specific surface marker profiles and growth factor secretions can be different. We hypothesized that MSCs derived from different sources might also have different neuroprotective potential.

OBJECTIVE

In this study, we extracted MSCs from rodent olfactory mucosa and compared their neuroprotective effects on auditory hair cell survival with MSCs extracted from rodent adipose tissue.

METHODS

Organ of Corti explants were dissected from 41 cochlea and incubated with olfactory mesenchymal stem cells (OMSCs) and adipose mesenchymal stem cells (AMSCs). After 72 hours, Corti explants were fixed, stained, and hair cells counted. Growth factor concentrations were determined in the supernatant and cell lysate using Enzyme-Linked Immunosorbent Assay (ELISA).

RESULTS

Co-culturing of organ of Corti explants with OMSCs resulted in a significant increase in inner and outer hair cell stereocilia survival, compared to control. Comparisons between both stem cell lines, showed that co-culturing with OMSCs resulted in superior inner and outer hair cell stereocilia survival rates over co-culturing with AMSCs. Assessment of growth factor secretions revealed that the OMSCs secrete significant amounts of insulin-like growth factor 1 (IGF-1). Co-culturing OMSCs with organ of Corti explants resulted in a 10-fold increase in IGF-1 level compared to control, and their secretion was 2 to 3 times higher compared to the AMSCs.

CONCLUSIONS

This study has shown that OMSCs may mitigate auditory hair cell stereocilia degeneration. Their neuroprotective effects may, at least partially, be ascribed to their enhanced IGF-1 secretory abilities compared to AMSCs.

摘要

重要性

间充质干细胞(MSCs)具有为退化组织提供持续旁分泌支持的能力。由于 MSCs 可以从广泛的组织中提取,因此它们的特定表面标志物谱和生长因子分泌可能不同。我们假设,源自不同来源的 MSCs 可能也具有不同的神经保护潜力。

目的

在这项研究中,我们从啮齿动物嗅黏膜中提取 MSCs,并将其与从啮齿动物脂肪组织中提取的 MSCs 的听觉毛细胞存活的神经保护作用进行比较。

方法

从 41 个耳蜗中分离出 Corti 器官外植体,并与嗅间充质干细胞(OMSCs)和脂肪间充质干细胞(AMSCs)共培养。72 小时后,将 Corti 外植体固定、染色并计数毛细胞。使用酶联免疫吸附试验(ELISA)在上清液和细胞裂解物中测定生长因子浓度。

结果

与对照相比,Corti 外植体与 OMSCs 共培养可显著增加内毛细胞和外毛细胞静纤毛的存活率。比较两种干细胞系,与 AMSCs 共培养相比,与 OMSCs 共培养可导致内毛细胞和外毛细胞静纤毛存活率更高。生长因子分泌评估显示,OMSCs 分泌大量胰岛素样生长因子 1(IGF-1)。与 Corti 外植体共培养 OMSCs 可使 IGF-1 水平比对照增加 10 倍,其分泌量比 AMSCs 高 2 至 3 倍。

结论

本研究表明,OMSCs 可能减轻听觉毛细胞静纤毛变性。它们的神经保护作用至少部分归因于与 AMSCs 相比,其增强的 IGF-1 分泌能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f36/11177734/9a0faca2a2d7/10.1177_19160216241258431-img2.jpg

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