Background: Mesenchymal stem cells (MSCs) therapy is a novel treatment strategy for cancer and a wide range of diseases with an excessive immune response such as ulcerative colitis (UC), due to its powerful immunomodulatory properties and its capacity for tissue regeneration and repair. One of the promising therapeutic options can focus on MSC-secreted exosomes (MSC-Exo), which have been identified as a type of paracrine interaction. In light of a wide variety of recent experimental studies, the present review aims to seek the recent research advances of therapies based on the MSC-Exo for treating UC and colorectal cancer (CRC). Methods: A systematic literature search in MEDLINE, Scopus, and Google Scholar was performed from inception to December 2021 using the terms [(“colorectal cancer” OR “bowel cancer” OR “colon cancer” OR “rectal cancer”) AND (exosome) AND (stem cell) AND (“inflammatory bowel disease” OR “Crohn's disease” OR “colitis”)] in titles and abstracts. Findings: Exosomes derived from various sources of MSCs, including human umbilical cord-derived MSCs (hUC-MSCs), human adipose-derived MSCs (hAD-MSCs), human bone marrow-derived MSCs (hBM-MSCs), and olfactory ecto-MSCs (OE-MSCs), have shown the protective role against UC and CRC. Exosomes from hUC-MSCs, hBM-MSCs, AD-MSCs, and OE-MSCs have been found to ameliorate the experimental UC through suppressing inflammatory cells including macrophages, Th1/Th17 cells, reducing the expression of proinflammatory cytokines, as well as inducing the anti-inflammatory function of Treg and Th2 cells and enhancing the expression of anti-inflammatory cytokines. In addition, hBM-MSC-Exo and hUC-MSC-Exo containing tumor-suppressive miRs (miR-3940-5p/miR-22-3p/miR‐16‐5p) have been shown to suppress proliferation, migration, and invasion of CRC cells via regulation of RAP2B/PI3K/AKT signaling pathway and ITGA2/ITGA6. Key messages: The MSC-Exo can exert beneficial effects on UC and CRC through two different mechanisms including modulating immune responses and inducing anti-tumor responses, respectively.

Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the present study was to investigate the potential of berberine against n-STZ-induced painful diabetic peripheral polyneuropathy by assessing various biochemical, electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in T2DM-induced neuropathic pain reflected by a significant alterations (P < .05) in hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities whereas berberine (20 and 40 mg/kg) treatment significantly attenuated (P < .05) these alterations. Berberine treatment significantly inhibited (P < .05) STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative stress and decreased Na-K-ATPase and pulse Ox levels were significantly attenuated (P < .05) by berberine. It also significantly downregulated (P < .05) neural tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 messenger RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), and peroxisome proliferator-activated receptors-γ (PPAR-γ) in sciatic nerve were significantly upregulated (P < .05) by berberine. Western blot analysis revealed that STZ-induced alterations in adenosine monophosphate protein kinase (AMPK; Thr-172) and protein phosphatase 2C-α protein expressions in dorsal root ganglia were inhibited by berberine. It also attenuated histological and ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, berberine exerts its neuroprotective effect against n-STZ-induced diabetic peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF α, IL-1β, and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-γ, and AMPK expression to ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during T2DM.

Acute liver failure (ALF) is a complicated clinical syndrome associated with high mortality, with liver transplantation as the only treatment option. Treatment of mesenchymal stem cells has shown a potential therapeutic option for acute liver failure. However, the lack of random clinical trials and large non-human primate studies makes it necessary to assess the efficacy and safety in the clinic. We treated the monkeys with peripheral delivery of human umbilical MSCs (hUC-MSCs) and investigated the role of hUC-MSCs in modulating the progress of acute liver failure. The use of early peripheral infusion of human umbilical cord MSC infusion did not improve liver regeneration or modulate adaptive immunity. However, it significantly suppressed the hepatic aggregation and maturation of circulating monocytes and their IL-6 secretion, greatly improving liver histology, systemic homeostasis, and survival. Our study reveals the critical role of monocyte-derived IL-6 in initiating and accelerating acute liver failure and hUC-MSC treatment can disrupt the development of the inflammatory cascade by inhibiting monocyte activation. Early hUC-MSC treatment disrupts the development of the inflammatory cascade, indicating a potential clinical solution for acute liver failure.

Barrett’s esophagus (BE) is a precancerous lesion of esophageal adenocarcinoma (EAC). It is a pathological change in which the squamous epithelium distal esophagus is replaced by columnar epithelium. Loss of P53 is involved in the development of BE and is taken as a risk factor for the progression. We established a HET1A cell line with P53 stably knockdown by adenovirus vector infection, followed by 30 days of successive acidic bile salt treatment. MTT, transwell assay, and wound closure assay were applied to assess cell proliferation and migration ability. The expression of key factors was analyzed by RT-qPCR, western blotting and immunohistochemical staining. Our data show that the protein expression level of P53 reduced after exposure to acidic bile salt treatment, and the P53 deficiency favors the survival of esophageal epithelial cells to accommodate the stimulation of acidic bile salts. Furthermore, exposure to acidic bile salt decreases cell adhesions by repressing the JAK/STAT signaling pathway and activating VEGFR/AKT in P53-deficient esophageal cells. In EAC clinical samples, P53 protein expression is positively correlated with that of ICAM1 and STAT3 and negatively correlated with VEGFR protein expression levels. These findings elucidate the role of P53 in the formation of BE, explain the mechanism of P53 deficiency as a higher risk of progression for BE formation, and provide potential therapeutic targets for EAC.