Bone Marrow Mesenchymal Stem Cells Exosomes Research Articles

Exosomal miR-455-3p from BMMSCs prevents cardiac ischemia-reperfusion injury

Bone marrow mesenchymal stem cells (BMMSCs) exert protective effects against myocardial infarction (MI). Here, we focused on the function and mechanism of miR-455-3p from BMMSCs-derived exosomes (BMMSCs-Exo) in myocardial infarction. BMMSCs were isolated from rat bone marrow, and the exosomes from the culture medium of BMMSCs were separated, and administered to H9C2 cells under hypoxia-reperfusion (H/R) stimulation. MTT and TUNEL staining analyzed cell viability and apoptosis, respectively. RT-qPCR determined miR-455-3p expression. Apoptosis-related proteins, autophagy-associated proteins, and the MEKK1-MKK4-JNK signaling pathway were detected. The interaction between miR-455-3p and MEKK1 was confirmed through dual luciferase activity and RIP assay. An in vivo ischemia reperfusion (I/R) model was established in rats. 2, 3, 5 triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, Masson staining, and TUNEL staining evaluated the infarct volume and histopathological changes. miR-455-3p's expression was down-regulated in BMMSCs-derived exosomes, I/R myocardial tissues, and H/R myocardial cells. miR-455-3p enriched by BMMSC exosomes reduced H/R-mediated cardiomyocyte damage and death-related autophagy. miR-455-3p upregulation suppressed MEKK1-MKK4-JNK. MEKK1 overexpression notably mitigated cell apoptosis, cramped cell viability, suppressed autophagy expansion, and attenuated Exo-miR-455-3p's protection on H/R myocardial cells. In-vivo trials reflected that BMMSC exosomes enriched with miR-455-3p repressed ischemia reperfusion-induced myocardial damage and myocardial cell function. miR-455-3p, shuttled by exosomes from MSCs, targets the MEKK1-MKK4-JNK signaling pathway to guard against myocardial ischemia-reperfusion damage.

MiR-375 Enriched in Bone Marrow Mesenchymal Stem Cells (BMSC) Exosomes Inhibits Prostate Cancer Cell Migration and Invasion by Down-Regulating Trefoil Factor 3 (TFF3)

To study the effect and mechanism of miR-375 enriched in BMSC exosomes on prostate cancer (PC) cells. Bioinformatics assessed the potential regulatory miRNA of TFF3 and miR-375 level in breast cancer cells and breast cancer clinical samples was detected by PCR. Dual luciferase assay validated the relationship between TFF3 and miR-375. miR-375 mimics or sh-TFF3 was transfected into PC cells, followed by measuring miR-375 and TFF3 by PCR and Western-blot. Cell proliferation, invasion, migration and apoptosis by Edu staining, transwell and flow cytometry. The BMSC exosomes were then isolated and co-cultured with PC cells to detect cell proliferation and invasion. PC cells and tissues showed the expression of miR-375 was decreased, indicated that miR-375 specifically inhibited TFF3 level. miR-375 was enriched in MSC-derived exosomes and could be transferred to PC cells. miR-375 mimics, exosome miR-375 or silenced TFF3 inhibited TFF3 level, up-regulated PCNA, MMP-2/9 expression, thereby inhibiting cell proliferation and metastasis, and promoting cell apoptosis. miR-375 is enriched in BMSC exosomes and inhibits PC cell migration and invasion by reducing TFF3.

Bone marrow mesenchymal stem cell-derived exosomes inhibit chondrocyte apoptosis and the expression of MMPs by regulating Drp1-mediated mitophagy

Osteoarthritis (OA) is a joint degenerative disease commonly seen in the elderly. Bone marrow mesenchymal stem cell-exosomes (BMSC-exosomes) are closely associated with the progression of OA. Here, we investigated whether BMSC-exosomes can affect OA development by regulating mitophagy. Primary rat chondrocytes were treated with advanced glycation end products (AGEs) to induce cell damage. The results of flow cytometry showed that AGEs treatment significantly promoted apoptosis of chondrocytes. AGEs treatment also enhanced the expression of matrix metalloproteinases (MMPs), MMP-3 and MMP-13, and dynamin-related protein 1 (Drp1) in chondrocytes. To investigate the impact of BMSC-exosomes on chondrocytes, chondrocytes were treated with BMSC-exosomes. AGEs-mediated increase of apoptosis and up-regulation of MMP-3, MMP-13, and Drp1 in chondrocytes were abrogated by BMSC-exosomes. Western blot analysis of autophagy-related proteins and Mito-Keima assay revealed that BMSC-exosome treatment elevated the expression of autophagy-related proteins, LC3-II/LC3-I and Beclin-1, and promoted mitophagy in the AGEs-treated chondrocytes. Moreover, Drp1 overexpression repressed the expression of LC3-II/LC3-I and Beclin-1, and enhanced apoptosis and the expression of MMP-3 and MMP-13 in AGEs-treated chondrocytes. BMSC-exosomes reversed the impact of Drp1 overexpression on AGEs-treated chondrocytes. In conclusion, this work demonstrates that BMSC-exosomes inhibit chondrocyte apoptosis and the expression of MMPs, which attributes to regulate Drp1-mediated mitophagy. Thus, BMSC-exosomes may be a potential treatment for OA.

Exosomes Secreted by Mesenchymal Stem Cells Induce Immune Tolerance to Mouse Kidney Transplantation via Transporting LncRNA DANCR.

Mesenchymal stem cells induce kidney transplant tolerance by increasing regulatory T (Treg) cells. Bone marrow mesenchymal stem cell exosomes (BMMSC-Ex) promote Treg cell differentiation. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is expressed in BMMSCs and can be encapsulated in exosomes. We aimed to explore the role of DANCR in BMMSC-Ex in immune tolerance after kidney transplantation and related mechanism. The isogenic/allograft kidney transplantation mouse model was established, and levels of serum creatinine (SCr) were determined. Hematoxylin-eosin staining was conducted to detect the inflammation, and immunohistochemistry was performed to detect the infiltration of CD4+ T cells. Levels of IFN-γ, IL-17, and IL-2 were examined by ELISA. Flow cytometry was conducted to determine Treg cells. In the allograft group, the inflammatory response was severe, CD4+ T cell infiltration, SCr levels, and plasma rejection-related factors were up-regulated, while injection of BMMSC-Ex reversed the results. BMMSC-Ex increased Treg cells in kidney transplantation mice. Interference with DANCR reversed the promoting effect of BMMSC-Ex on Treg cell differentiation. DANCR bound to SIRT1, promoted ubiquitination and accelerated its degradation. The injection of BMMSC-Ex (after interference with DANCR) promoted SIRT1 levels, inflammatory response, CD4+ T cell infiltration, SCr levels, and plasma rejection related factors' expression, while Treg cells were decreased. LncRNA DANCR in BMMSC-Ex promoted Treg cell differentiation and induced immune tolerance of kidney transplantation by down-regulating SIRT1 expression in CD4+ T cells.

Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis.

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in clinical models of osteoarthritis (OA). However, effects of MSC‐derived exosomes on OA remain unclear. The study aimed to investigate the therapeutic potential of exosomes from human bone marrow MSCs (BM‐MSCs) in alleviating OA. The anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery were performed on the knee joints of a rat OA model, followed by intra‐articular injection of BM‐MSCs or their exosomes. In addition, BM‐MSC‐derived exosomes were administrated to primary human chondrocytes to observe the functional and molecular alterations. Both of BM‐MSCs and BM‐MSC‐derived exosomes alleviated cartilage destruction and subchondral bone remodelling in OA rat model. Administration of BM‐MSCs and exosomes could reduce joint damage and restore the trabecular bone volume fraction, trabecular number and connectivity density of OA rats. In addition, in vitro assays showed that BM‐MSCs‐exosomes could maintain the chondrocyte phenotype by increasing collagen type II synthesis and inhibiting IL‐1β–induced senescence and apoptosis. Furthermore, exosomal lncRNA MEG‐3 also reduced the senescence and apoptosis of chondrocytes induced by IL‐1β, indicating that lncRNA MEG‐3 might partially account the anti‐OA effects of BM‐MSC exosomes. The exosomes from BM‐MSCs exerted beneficial therapeutic effects on OA by reducing the senescence and apoptosis of chondrocytes, suggesting that MSC‐derived exosomes might provide a candidate therapy for OA treatment.

Therapeutic effect of co-culture of rat bone marrow mesenchymal stem cells and degenerated nucleus pulposus cells on intervertebral disc degeneration

BackgroundAfter non-contact co-culture of bone marrow mesenchymal stem cells (BMSCs) with nucleus pulposus cells (NPCs), exosomes secreted by BMSCs were able to ameliorate the degree of disc degeneration. The reason for this is, at least in part, that exosomes from BMSCs achieve by affecting the level of autophagy in NPCs, while the components in exosomes are diverse and their specific mechanism of action is still unclear. PurposeHere, we aimed to explore the therapeutic effect of co-culture of BMSCs and NPCs on NPCs and explore its specific mechanism of action. Study design/SettingIn vitro study. MethodsRat NPCs and BMSCs were isolated and cultured in vitro. The serum deprivation experiment (using oxygen, glucose, and serum deprivation [OGD]) simulates the pathological state of low blood supply of the intervertebral disc in vivo. We used apoptotic cell staining and flow cytometry to study the effect of BMSCs on the apoptosis rate of rat NPCs, and the apoptotic proteins active-caspase-3, active-caspase-9, autophagy marker proteins LC3 and Beclin 1 were further detected using Western blot analysis. The expression levels of the pro-apoptotic protein Bax and the apoptosis-inhibiting protein Bcl2 were measured. The differentially expressed miRNAs were screened in a gene expression profiling chip. Then qRT-PCR was used to detect the effect of different treatment methods on miR-155 expression. The effect of anti-miR-155 antibodies on autophagy was studied by flow cytometry and transmission electron microscopy. A luciferase reporter assay was used to study the direct interaction between miR-155 and BACH1 mRNA, which was analyzed by TargetScan software, and the results were verified by Western blotting. ResultsCompared with the OGD group, the expression level of miR-155 and the NPC autophagy level significantly increased; the HO-1 protein expression increased; and the Bach1 protein expression, degeneration index, and apoptosis index all significantly decreased in the co-culture group. After BMSCs transfected with anti-miR-155 were co-cultured with NPCs, the miR-155 expression in the cells was significantly reduced, the HO-1 protein expression and the level of cell autophagy was reduced. However, Bach1 protein expression, NPC degeneration index, and apoptosis index increased. After being inhibited by the autophagy inhibitor wortmannin, the cell degeneration index and apoptosis rate significantly improved. ConclusionIn the OGD model, BMSCs can significantly increase the viability, the level of autophagy, and reduce the level of apoptosis in rat NPCs. BMSC exosomes increase miR-155 expression in NPCs, which targets Bach1 and in turn upregulates HO-1 expression, activates autophagy in NPCs, inhibits the apoptosis level, and improves intervertebral disc degeneration. Clinical SignificanceOur experiment shows that it is maybe feasible to treat disc degeneration with drugs. At the same time, compared with BMSC injection method of treatment, side effects of drug therapy are smaller, and can be controlled, it also provides a new way for intervertebral disc degeneration drug treatment.

Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway.

Mesenchymal stem cells (MSCs) have been described to induce angiogenesis in various tissues and have been used for the development of novel cell‐based therapies. Increasing evidence suggests that MSCs execute their paracrine function via the secretion of exosomes, especially under hypoxic conditions. However, the mechanisms by which MSC‐derived exosomes secreted under hypoxia enhance angiogenesis still remain unclear. To study exosome physiology under hypoxic or normoxic conditions, we isolated exosomes from bone marrow mesenchymal stem cells (BMSCs). Furthermore, we detected the uptake of exosomes by human umbilical vein endothelial cells (HUVECs) by immunofluorescence staining. In addition, we determined the effects of exosomes on cell viability, migration and tube formation in HUVECs by Cell Counting Kit‐8, migration and tube formation assays, respectively. We examined the expression of key proteins related to exosome‐induced angiogenesis by BMSCs cultured under hypoxic conditions by western blot. Exosomes released by BMSCs cultured under hypoxic conditions enhanced cell proliferation, migration and angiogenesis of HUVECs. Hypoxia induced the expression of high mobility group box 1 protein (HMGB1) in BMSC‐derived exosomes, and silencing of HMGB1 abolished the angiogenic effect in HUVECs. Furthermore, exosomal HMGB1 activated the JNK signaling pathway and induced hypoxia‐inducible factor‐1α/vascular endothelial growth factor expression, consequently enhancing angiogenesis in HUVECs. Our data reveal that exosomal HMGB1 promotes angiogenesis via JNK/hypoxia‐inducible factor‐1α signaling. Therefore, BMSC exosomes derived under hypoxia may have potential for development of novel treatment strategies for angiogenesis‐related diseases.

Bone Marrow Mesenchymal Stem Cells-Derived Exosomal MicroRNA-150-3p Promotes Osteoblast Proliferation and Differentiation in Osteoporosis

At present, much more studies have focused on the role of microRNAs in osteoporosis, but the more specific role of microRNA-150-3p (miR-150-3p) in osteoporosis still needs full exploration. We aim at investigating the role of miR-150-3p in osteoporosis and at exploring the related mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which exosomes were isolated. Osteoporosis models were established by ovariectomy and injected with transfected BMSCs exosomes. Bone formation markers in serum, histopathological changes and miR-150-3p, runt-related transcription factor 2 (Runx2) and Osterix expression, and osteoblast apoptosis in femoral tissues were detected. Osteoblasts were isolated and co-cultured with the transfected BMSCs-derived exosomes. Osteoblast proliferation, cell differentiation, and apoptosis, along with miR-150-3p, Runx2, and Osterix expression in osteoblasts were detected. In vivo experiment demonstrated that miR-150-3p, Runx2, and Osterix expression was decreased whereas bone formation markers were decreased in osteoporosis. BMSCs exosomes attenuated osteoporosis, which was further improved by upregulated miR-150-3p in exosomes whereas it was impaired by downregulated miR-150-3p in exosomes. In vitro experiments declared decreased miR-150-3p, Runx2, and Osterix expression; suppressed proliferation; and encouraged apoptosis in osteoblasts in osteoporosis. BMSCs exosomes promoted osteoblast proliferation and differentiation and inhibited apoptosis, which was strengthened by raised exosomal miR-150-3p whereas it was disrupted by inhibited exosomal miR-150-3p. Our study elucidates that exosomal miR-150-3p promotes osteoblast proliferation and differentiation in osteoporosis and provides a new clue for the treatment of patients with osteoporosis.

Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment

Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.

Mesenchymal stem cells-derived exosomes ameliorate nucleus pulposus cells apoptosis via delivering miR-142-3p: therapeutic potential for intervertebral disc degenerative diseases

ABSTRACT Intervertebral disc degeneration (IDD) is the main cause of lower back pain (LBP), and puzzles massive individuals worldwide. Mesenchymal stem cells (MSCs) transplantation has been demonstrated to potentially ameliorate IDD progression, while the underlying mechanism has not been fully explained. Interleukin-1β (IL-1β) was used to induce nucleus pulposus cells (NPCs) injury. Bone marrow MSCs-derived exosomes were isolated using the super centrifugation method, and characterized using Transmission electron microscopy (TEM) and western blot. Cell viability was determined by MTT, while apoptosis was measured by Annexin-V staining using flow cytometry. miR-142-3fp and gene expressions were measured by real-time PCR. The protein expressions were determined by western blot. Herein, we found exosomes from bone marrow MSCs are circular vesicles, about 80 nm in diameter, and with robust expression of TSG101 and CD63, but without of Calnexin. MSCs exosomes alleviated NPCs apoptosis by reducing IL-1β-induced inflammatory cytokines secretion and MAPK signaling activation. Additionally, MSCs exosomes inhibited NPCs apoptosis and MAPK signaling by delivering miR-142-3p that targets mixed lineage kinase 3 (MLK3). Overexpression of MLK3 abolished the effects of MSCs exosomes on the inflammatory condition, cell apoptosis, and MAPK signaling activation in NPCs. The results confirmed that bone marrow MSCs-derived exosomes-packaged miR-142-3p alleviates NPCs injury through suppressing MAPK signaling by targeting MLK3. The work highlights the therapeutic effect of MSCs on IDD progression, and bone marrow MSCs exosomes might be apromising therapeutic strategy for IDD.

RETRACTED: Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-126-3p Inhibits Pancreatic Cancer Development by Targeting ADAM9

Pancreatic cancer is a lethal malignancy with relatively few effective therapies. Recent investigations have highlighted the role of microRNAs (miRNAs) as crucial regulators in various tumor processes including tumor progression. Hence the current study aimed to investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomal microRNA-126-3p (miR-126-3p) in pancreatic cancer. Initially, miRNA candidates and related genes associated with pancreatic cancer were screened. PANC-1 cells were transfected with miR-126-3p or silenced a disintegrin and a metalloproteinase-9 (ADAM9) to examine their regulatory roles in pancreatic cancer cells. Additionally, exosomes derived from BMSCs were isolated and co-cultured with pancreatic cancer cells to elucidate the effects of exosomes in pancreatic cancer. Furthermore, the effects of overexpressed miR-126-3p derived from BMSCs exosomes on proliferation, migration, invasion, apoptosis, tumor growth, and metastasis of pancreatic cancer cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo. Restored miR-126-3p was observed to suppress pancreatic cancer through downregulating ADAM9. Notably, overexpressed miR-126-3p derived from BMSCs exosomes inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells, and promoted their apoptosis both in vitro and in vivo. Taken together, the key findings of the study indicated that overexpressed miR-126-3p derived from BMSCs exosomes inhibited the development of pancreatic cancer through the downregulation of ADAM9, highlighting the potential of miR-126-3p as a novel biomarker for pancreatic cancer treatment.

Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia

Multiple sclerosis (MS) is a chronic demyelinating disease caused by central nervous system (CNS) inflammation and immune dysfunction, which often leaves patients with severe physical disabilities. Microglia function in the surveillance of the CNS, and an imbalance in the M1/M2 phenotypes of microglia contribute to the progression of MS. Recent studies indicate that exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) play therapeutic roles in many autoimmune diseases and aid in tissue repair. However, it is not clear whether BMSC-derived exosomes can attenuate MS-associated inflammation and immune dysfunction, or how BMSC exosomes protect neurons. The experimental autoimmune encephalomyelitis (EAE) rat model was used to investigate the effect of exosomes on microglia polarization and inflammation in CNS. The results showed that exosome treatment significantly decreased neural behavioral scores, reduced the infiltration of inflammatory cells into the CNS, and decreased demyelination in comparison to untreated EAE rats. In addition, exosome treatment resulted in significant increases in the levels of M2-related cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β, whereas M1-related tumor necrosis factor (TNF)-α and IL-12 levels decreased significantly. Moreover, compared with the untreated EAE group, the exosome group displayed significantly increased protein and mRNA expression levels of M2 phenotype markers, whereas M1 marker expression decreased. Our findings were further confirmed in an in vitro HAPI microglia cell line model. In conclusion, these findings indicate that BMSC-derived exosomes can attenuate inflammation and demyelination of the CNS in the EAE rat model by regulating the polarization of microglia. Therefore, the use of BMSC-derived exosomes may be a potential therapeutic approach for the treatment of autoimmune and inflammatory diseases.

Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis.

Neurodegenerative diseases comprise a group of disorders for which no treatment is available till date. Stem cell based therapy offers great hope and promise. However, stem cell transplantation is associated with certain disadvantages like poor targeted migration, engraftment and survival of the transplanted cells. Exosomes, a type of extracellular membrane vesicle released by all cell types including stem cells, offer an alternative to stem cell transplantation. Exosome carry a wide array of biomolecules and are implicated in exhibiting substantial benefits in the repair/regeneration of the injured tissue. Thus, exosomes offer an alternative therapeutic approach as a substitute of cell transplantation. In order to utilize exosomes for therapeutic purpose, it is essential to evaluate the appropriate passage number and the dosage to avoid possible cytotoxic effects. Here, we isolated exosomes from different passages of rat bone marrow mesenchymal stem cells (BM-MSC) and analysed the neuroprotective potential of BM-MSC exosomes in an in vitro model of excitotoxicity. Our results demonstrated that the exosomes isolated from early passage of rat BM-MSC exhibited more efficient neuroprotective potential as opposed to later passages derived exosomes. Furthermore, the neuroprotective efficacy of exosome is dosage dependent. i.e. the lower dosage of exosomes was found to be neuroprotective, whereas higher dosage of exosomes (from later passages) was found to be detrimental to neurons. The early passage derived exosomes protected neurons through anti-apoptotic, anti-necrotic and anti-oxidant mechanisms. Our study suggests that adult stem cells derived exosomes could be a potential therapeutic agent to confer neuroprotection in neurodegenerative diseases like Alzheimer's disease.

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

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.