Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells

Abstract

BackgroundThe stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell–cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells.MethodsThe exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively.ResultsBoth the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs.ConclusionOur study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

“…Studies have revealed that MSC medium may contain a large amount of protective factors for NICCs exposed to hypoxic damage, 51 and exosomes are one example. 52,53 Exosomes are membrane- clinically relevance, we have tested clinical serum-free medium (Cell Therapy Systems STEMPRO MSC SFM CTS medium (Thermofisher, A10332-01) in our culture system and achieved similar results to that presented in this study. Exosomes derived from MSCs might be an efficient nutrient delivery vehicle for graft islets, and may become a promising strategy to improve the outcome of islet transplantation.…”

“…Studies have revealed that MSC medium may contain a large amount of protective factors for NICCs exposed to hypoxic damage, and exosomes are one example . Exosomes are membrane‐enclosed nanovesicles (50‐200 nm diameter in our test) that shuttle active cargo between different cells.…”

Mechanisms of endogenous repair failure during intervertebral disc degeneration

“…And it was demonstrated that MSCs influenced NP cells via paracrine manner, cell contact, and cell fusion, promoting NP cells to secrete cytokines that induced the differentiation of stem cells to NP-like cells, and these cytokines could also facilitate NP-like cells to repair IVD degeneration 84,85 . It was also reported that NP cells could secrete exosomes to induce bone marrow-derived MSCs differentiation to NP-like cells and promote bone marrow-derived MSCs migration 86 .…”

Exosomes: biology, therapeutic potential, and emerging role in musculoskeletal repair and regeneration

“…It was reported that NPC‐derived exosomes promoted MSC migration and stimulated MSCs to differentiate to a nucleus pulposus–like phenotype. MSC‐derived exosomes also stimulated the NPCs to regain a nondegenerate phenotype and enhance extracellular matrix production . This study suggests that the exosome‐based, cell‐free/progenitor therapeutic approach bears potential for IVD treatment.…”

“…MSCderived exosomes also stimulated the NPCs to regain a nondegenerate phenotype and enhance extracellular matrix production. 88 This study suggests that the exosome-based, cell-free/progenitor therapeutic approach bears potential for IVD treatment.…”