UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

Koh, Kyungmin; Park, Soo‐Jin; Bae, Eun Soo; Duong, Van-An; Park, Jong; Lee, Hookeun; Lew, Helen

doi:10.1186/s13287-020-01943-w

Cited by 14 publications

(11 citation statements)

References 54 publications

(66 reference statements)

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“…1c ). Western blot analysis demonstrated that the exosome surface proteins CD63, CD9 and TSG101 42 , 43 were expressed in the 2D- and 3D-exos, but the cytosolic marker GM130 was absent in the 2D- and 3D-exos (Fig. 1d ).…”

Section: Resultsmentioning

confidence: 96%

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium

Zhang

Chen

et al. 2021

Int J Oral Sci

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Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.

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Section: Resultsmentioning

confidence: 96%

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium

Zhang

Chen

et al. 2021

Int J Oral Sci

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“…Previously, we demonstrated the therapeutic efficacy of exosomes from MSCs. They enhanced the neuroprotective and neurorecovery abilities of in vitro models [29]. UBA2 expression is increased in a time-dependent manner in response to hypoxia, and is upregulated in the exosome [1].…”

Section: Discussionmentioning

confidence: 95%

Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model

Park

Kim

Shin

et al. 2021

IJMS

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Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using R28 cells under hypoxic conditions and a rat model of optic nerve injury. NPCs and PSCs (2 × 106 cells) were injected into the subtenon space. After 1, 2, and 4 weeks, we examined changes in target proteins in the retina and optic nerve. NPCs significantly induced vascular endothelial growth factor (Vegf) compared to age-matched shams and PSC groups at 2 weeks; they also induced neurofilaments in the retina compared to the sham group at 4 weeks. In addition, the expression of brain-derived neurotrophic factor (Bdnf) was high in the retina in the NPC group at 2 weeks, while expression in the optic nerve was high in both the NPC and PSC groups. The low expression of ionized calcium-binding adapter molecule 1 (Iba1) in the retina had recovered at 2 weeks after NPC injection and at 4 weeks after PSC injection. The expression of the inflammatory protein NLR family, pyrin domain containing 3 (Nlrp3) was significantly reduced at 1 week, and that of tumor necrosis factor-α (Tnf-α) in the optic nerves of the NPC group was lower at 2 weeks. Regarding retinal ganglion cells, the expressions of Brn3a and Tuj1 in the retina were enhanced in the NPC group compared to sham controls at 4 weeks. NPC injections increased Gap43 expression from 2 weeks and reduced Iba1 expression in the optic nerves during the recovery period. In addition, R28 cells exposed to hypoxic conditions showed increased cell survival when cocultured with NPCs compared to PSCs. Both Wnt/β-catenin signaling and increased Nf-ĸb could contribute to the rescue of damaged retinal ganglion cells via upregulation of neuroprotective factors, microglial engagement, and anti-inflammatory regulation by NPCs. This study suggests that NPCs could be useful for the cellular treatment of various optic neuropathies, together with cell therapy using mesenchymal stem cells.

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“…If samples containing proteins are culture media, exosomes, or body fluids such as serum, plasma, saliva, tears, nasal fluids, urine, or aqueous humor, they do not require lysis pretreatment. In these cases, an appropriate amount of buffer is added to favor subsequent enzymatic digestion steps [63,64]. If samples are cells, a lysis step is applied to break the cell membrane.…”

Section: Sampling and Sample Pretreatmentmentioning

confidence: 99%

Proteomics in Forensic Analysis: Applications for Human Samples

et al. 2021

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Proteomics, the large-scale study of all proteins of an organism or system, is a powerful tool for studying biological systems. It can provide a holistic view of the physiological and biochemical states of given samples through identification and quantification of large numbers of peptides and proteins. In forensic science, proteomics can be used as a confirmatory and orthogonal technique for well-built genomic analyses. Proteomics is highly valuable in cases where nucleic acids are absent or degraded, such as hair and bone samples. It can be used to identify body fluids, ethnic group, gender, individual, and estimate post-mortem interval using bone, muscle, and decomposition fluid samples. Compared to genomic analysis, proteomics can provide a better global picture of a sample. It has been used in forensic science for a wide range of sample types and applications. In this review, we briefly introduce proteomic methods, including sample preparation techniques, data acquisition using liquid chromatography-tandem mass spectrometry, and data analysis using database search, spectral library search, and de novo sequencing. We also summarize recent applications in the past decade of proteomics in forensic science with a special focus on human samples, including hair, bone, body fluids, fingernail, muscle, brain, and fingermark, and address the challenges, considerations, and future developments of forensic proteomics.

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UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

Cited by 14 publications

References 54 publications

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium

Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model

Proteomics in Forensic Analysis: Applications for Human Samples

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