Exosomes derived from differentiated human ADMSC with the Schwann cell phenotype modulate peripheral nerve-related cellular functions

Authors

Bo Liu, University of Nebraska Medical CenterFollow
Yunfan Kong, University of Nebraska Medical Center
Wen Shi, University of Nebraska Medical CenterFollow
Mitchell Kuss, University of Nebraska Medical CenterFollow
Ke Liao, University of Nebraska Medical Center
Guoku Hu, University of Nebraska Medical CenterFollow
Peng Xiao, University of Nebraska Medical CenterFollow
Jagadesan Sankarasubramanian, University of Nebraska Medical CenterFollow
Chittibabu Guda, University of Nebraska Medical CenterFollow
Xinglong Wang, University of Nebraska Medical Center
Yuguo Lei, Pennsylvania State University
Bin Duan, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

11-23-2022

Citation

Bioactive Materials 14 (2022) 61–75. https://doi.org/10.1016/j.bioactmat.2021.11.022

Comments

Open access

Abstract

Peripheral nerve regeneration remains a significant clinical challenge due to the unsatisfactory functional recovery and public health burden. Exosomes, especially those derived from mesenchymal stem cells (MSCs), are promising as potential cell-free therapeutics and gene therapy vehicles for promoting neural regeneration. In this study, we reported the differentiation of human adipose derived MSCs (hADMSCs) towards the Schwann cell (SC) phenotype (hADMSC-SCs) and then isolated exosomes from hADMSCs with and without differentiation (i.e., dExo vs uExo). We assessed and compared the effects of uExo and dExo on antioxidative, angiogenic, antiinflammatory, and axon growth promoting properties by using various peripheral nerve-related cells. Our results demonstrated that hADMSC-SCs secreted more neurotrophic factors and other growth factors, compared to hADMSCs without differentiation. The dExo isolated from hADMSC-SCs protected rat SCs from oxidative stress and enhanced HUVEC migration and angiogenesis. Compared to uExo, dExo also had improved performances in downregulating pro-inflammatory gene expressions and cytokine secretions and promoting axonal growth of sensory neurons differentiated from human induced pluripotent stem cells. Furthermore, microRNA (miRNA) sequencing analysis revealed that exosomes and their parent cells shared some similarities in their miRNA profiles and exosomes displayed a distinct miRNA signature. Many more miRNAs were identified in dExo than in uExo. Several upregulated miRNAs, like miRNA-132-3p and miRNA-199b-5p, were highly related to neuroprotection, anti-inflammation, and angiogenesis. The dExo can effectively modulate various peripheral nerverelated cellular functions and is promising for cell-free biological therapeutics to enhance neural regeneration.