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In this contribution, we developed an injectable hydrogel composed of sodium alginate and hyaluronic acid that acts as a tissue scaffold to create a more optimal microenvironment for the stem cells for potential application of traumatic brain injury implantation.

Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer’s disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.

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Although Porphyromonas gingivalis lipopolysaccharide (P-LPS) is known to inhibit osteoblast differentiation, the exact molecular mechanisms underlying this phenomenon remain unclear. Here, we investigated the role of Notch signaling in the osteoblastic differentiation of both MC3T3E-1 cells and primary mouse bone marrow stromal cells (BMSCs). P-LPS stimulation activated the Notch1 signaling cascade and increased expression of the Notch target genes HES1 and HEY1. P-LPS can also act as an inhibitor because it is capable of suppressing Wnt/beta-catenin signaling in preosteoblasts by decreasing both glycogen synthase kinase-3beta (GSK-3beta) phosphorylation and the expression of nuclear beta-catenin. These effects were rescued, however, by inhibiting Notch1 signaling. Furthermore, P-LPS treatment inhibited osteoblast differentiation in preosteoblasts as demonstrated by reductions in alkaline phosphatase activity, osteoblast gene expression, and mineralization, all of which were rescued by suppression of Notch1 signaling. Moreover, inhibition of GSK-3beta, HES1, or HEY1 partially reversed the P-LPS-induced inhibition of osteoblast differentiation. Together, these findings suggest that P-LPS inhibits osteoblast differentiation by promoting the expression of Notch target genes and suppressing canonical Wnt/beta-catenin signaling.

Lipopolysaccharide (LPS) has been shown to be a prominent pathogenic factor in inflammatory bone loss. However, knowledge of the mechanisms involved is limited. The role of the SDF-1/CXCR4 (Stromal-derived factor-1 and its unique chemokine receptor) axis in LPS-induced bone loss has not been studied. The aim of this study was to investigate the role of the SDF-1/CXCR4 axis in LPS-stimulated inflammatory bone loss. The results show that LPS does not influence the expression of SDF-1/CXCR4 in osteoblasts, but up-regulates the expression of CXCR4 in pre-osteoclasts via Toll-like receptor 4, which subsequently enhances pre-osteoclast migration. Moreover, LPS promoted RANKL-induced osteoclast differentiation partially through CXCR4 up-regulation. In conclusion, the present study demonstrated, for the first time, that the up-regulated expression of CXCR4 in pre-osteoclasts by LPS stimulation is involved in LPS-induced bone resorption.

Long non-coding RNAs (lncRNAs) are defined as non-coding transcripts (>200 nucleotides) that serve important roles in the proliferation and differentiation of stem cells. Hair follicle stem cells (HFTs) have multidirectional differentiation potential and are able to differentiate into skin, hair follicles and sebaceous glands, serving a role in skin wound healing. The aim of the present study was to analyze the regulatory role of lncRNA AK015322 (IncRNA5322) in HFTs and the potential mechanism of IncRNA5322‑mediated differentiation of HFTs. The results demonstrated that lncRNA5322 transfection promoted proliferation and differentiation in HFTs. It was identified that lncRNA5322 transfection upregulated the expression and phosphorylation of phosphoinositide 3‑kinase (PI3K) and protein kinase B (AKT) in HFTs. It was also observed that lncRNA5322 transfection upregulated microRNA (miR)‑21 and miR‑21 agonist (agomir‑21) eliminated lncRNA5322‑induced expression and phosphorylation of PI3K and AKT. The present study also demonstrated that agomir‑21 blocked IncRNA5322‑induced expression and phosphorylation of PI3K and AKT in HFTs. The results indicated that agomir‑21 transfection also suppressed the IncRNA5322‑induced proliferation and differentiation of HFTs. In conclusion, the results of the present study suggest that lncRNA5322 is able to promote the proliferation and differentiation of HFTs by targeting the miR‑21‑mediated PI3K‑AKT signaling pathway in HFTs.

BackgroundTraumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment.MethodsIn this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury.ResultsWe found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling.ConclusionMG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.