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

Bo Liu, Yunfan Kong, Wen Shi, Mitchell Kuss, Ke Liao, Guoku Hu, Peng Xiao, Jagadesan Sankarasubramanian, Chittibabu Guda, Xinglong Wang, Yuguo Lei, Bin Duan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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, anti-inflammatory, 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 nerve-related cellular functions and is promising for cell-free biological therapeutics to enhance neural regeneration.

Original languageEnglish (US)
Pages (from-to)61-75
Number of pages15
JournalBioactive Materials
Volume14
DOIs
StatePublished - Aug 2022

Keywords

  • Anti-inflammatory
  • Anti-oxidation
  • Axon growth
  • Neural regeneration
  • microRNA

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering

Fingerprint

Dive into the research topics of 'Exosomes derived from differentiated human ADMSC with the Schwann cell phenotype modulate peripheral nerve-related cellular functions'. Together they form a unique fingerprint.

Cite this