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With outstanding therapeutic potential in the tissue regeneration and anti-inflammation, mesenchymal stem cell-derived exosomes (MSC-EXOs) have emerged as a prominent therapeutic in recent. However, poor production yield and reproducibility have remained as significant challenges of their practical applications. To surmount these challenges, various alternative materials with stem cell-like functions, have been recently investigated, however, there has been no comprehensive analysis in these alternatives so far. Here, we discuss the recent progress of alternatives of MSC-EXOs, including exosomes and exosome-like nanovesicles from various biological sources such as plants, milk, microbes, and body fluids. Moreover, we extensively compare each alternative by summarizing their unique functions and mode of actions to suggest the expected therapeutic target and future directions for developing alternatives for MSC-EXOs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Jung, Yoo, Go, Park, Lee and Um.)

LAB were isolated from makgeolli locally produced around Jinju, Gyeongnam, S. Korea during spring of 2011. Randomly selected 11 isolates from MRS agar plates were identified first by API CHL 50 kits and then 16S rRNA gene sequencing. All 11 isolates were identified as Lactobacillus plantarum. Among them, ST4 grew in MRS broth with ethanol up to 10%, showing the highest alcohol resistance. L. plantarum ST4 was moderately resistant against acid and bile salts. When cellular proteins of L. plantarum ST4 under ethanol stress were analyzed by two-dimensional gel electrophoresis (2DE), the intensities of 6 spots increased, whereas 22 spots decreased at least 2-fold. Those 28 spots were identified by peptide mass fingerprinting (PMF). FusA2 (elongation factor G) increased 18.8-fold (6% ethanol) compared with control. Other proteins were AtpD (ATP synthase subunit beta), DnaK, GroEL, Tuf (elongation factor Tu), and Npr2 (NADH peroxidase), respectively. Among the 22 proteins decreased in intensities, lactate dehydrogenases (LdhD and LdhL1) were included.

A 2.5 kb aga gene encoding alpha-galactosidase (alpha- Gal) from Leuconostoc mesenteroides SY1 was cloned into pSJE, an E. coli-Leuconostoc shuttle vector. The recombinant plasmid, pSJEaga, was introduced into Leuconostoc citreum KCTC3526 (ATCC49370) by electroporation. Transcription level of aga was the highest in cells grown on raffinose (1%, w/v) followed by cells grown on galactose, melibiose, fructose, glucose, and sucrose. Western blot using antibodies against alpha-Gal showed similar results to slot-blot results and enzyme activity measurements. All the results indicated that the heterologous aga was successfully expressed in L. citreum and its transcription was under the carbon catabolite repression (CCR).

Conclusion: This study suggests for the first time that 1) IGF-I, IGFBP-4, and -5 alone and IGF-I+IGFBP-5 mixture stimulated hair cell survival and prevented neomycin-induced hair cell loss in the sensory epithelial culture of mouse utricles, 2) When administered together, IGFBP-4 diminished the effect of IGF-I, 3) In P3-5 mice utricle, IGF-I, IGFBP-4, and IGFBP-5 are expressed in the cytoplasm of hair cells. And Insulin/IGF-I Receptor is expressed in the nucleus of hair cells., Objectives: Several growth factors have been demonstrated to protect auditory sensory cells in vitro and in vivo from aminoglycoside toxicity. IGF-I is one of the most well-known mitogenic and protective substance working in the inner ear. However, there are no reports available regarding the function of IGFBPs in the inner ear. In the present study, the effects of IGFBP-4 and -5 on hair cell survival were investigated in mouse utriclular organ cultures., Materials and Methods: The amount of cellular damage and cell viability in vestibular organs were assessed by counting hair cells stained with a rhodamine-phalloidin probe. The expressions of IGFBP-4, IGFBP-5, IGF-IR, and IGF-I were localized by immunohistochemistry., Results: When treated with IGF-I, IGFBP-4, or IGFBP-5 for 24 h, explant culture showed hair cell survival rates of 136+/-18%, 140+/-15%, and 133+/-6%, respectively, compared to controls. Neomycin (1 mM) induced hair cell loss resulted in 45+/-17% of hair cell survival. However, pre-treatment of IGF-I, IGFBP-4, or -5 before neomycin insult showed survival rates of 113+/-14%, 98+/-8%, and 73+/-24%, respectively. Similar to IGF-I, IGFBP-4 and IGFBP-5 were significantly protective. IGFBP-4 and -5 immunoreactivities were observed in the cytoplasm of normal explanted vestibular hair cells as well as in the P3 mouse utricular hair cells in vivo.

Unlike mammals, avian cochlear hair cells can regenerate after acoustic overstimulation. The WDR1 gene is one of the genes suspected to play an important role in this difference. In an earlier study, we found that the WDR1 gene is over-expressed in the chick cochlea after acoustic overstimulation. The aim of this study was to compare the expression of WDR1 before and after acoustic overstimulation in the chick vestibule. Seven-day-old chicks were divided into three groups: normal group, damage group, and regeneration group. The damage and regeneration group was exposed to 120 dB SPL white noise for 5-6 hours. The damage group was euthanized shortly after the impulse, but the regeneration group was allowed to recover for 2 days. The utricle, saccule, and the three ampullae of each semicircular canal were dissected and immunohistochemically stained with anti-WD40 repeat protein 1 antibody. For quantitative analysis, immunoreactive densities were measured and quantitative real-time RT PCR was performed. WD40 repeat protein 1 expression was elevated in all the semicircular canals and utricle, two days after an acoustic overstimulation (P=0.001). WDR1 mRNA expression was 1.34 times higher in the regeneration group compared to the normal group, but it was not statistically significant. Exceptionally, WD40 repeat protein 1 expression did not increase in the saccule of the regeneration group. Elevated WDR1 expression in the avian vestibule may have a role in the hair cell regenerating ability as in the avian cochlea. A similar mechanism of hair cell regeneration may exist in the avian cochlea and vestibule.