Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells.

Stemness pertains to the intrinsic ability of mesenchymal stem cells (MSCs) to undergo self-renewal and differentiate into multiple lineages, while simultaneously impeding their differentiation and preserving crucial differentiating genes in a state of quiescence and equilibrium. Owing to their favorable attributes, including uncomplicated isolation protocols, ethical compliance, and ease of procurement, MSCs have become a focal point of inquiry in the domains of regenerative medicine and tissue engineering. As age increases or ex vivo cultivation is prolonged, the functionality of MSCs decreases and their stemness gradually diminishes, thereby limiting their potential therapeutic applications. Despite the existence of several uncertainties surrounding the comprehension of MSC stemness, considerable advancements have been achieved in the clarification of the potential mechanisms that lead to stemness loss, as well as the associated strategies for stemness maintenance. This comprehensive review provides a systematic overview of the factors influencing the preservation of MSC stemness, the molecular mechanisms governing it, the strategies for its maintenance, and the therapeutic potential associated with stemness. Finally, we underscore the obstacles and prospective avenues in present investigations, providing innovative perspectives and opportunities for the preservation and therapeutic utilization of MSC stemness.

Asiaticoside Attenuates Blood-Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury.

The blood-spinal cord barrier (BSCB) plays a vital role in the recovery of spinal cord function after spinal cord injury (SCI). Pericytes, pluripotent members of the neurovascular unit (NVU), receive signals from neighboring cells and are critical for maintaining CNS function. Therapeutic targets for the BSCB include endothelial cells (ECs) and glial cells, but few drugs target pericytes. This study was designed to explore whether asiaticoside has a positively effect on pericytes and the integrity of the BSCB. In this study, we found that asiaticoside could inhibit the loss of junction proteins just 1 day after SCI in vivo, but our in vitro study showed no significant differences in the expression of endothelial junction proteins between the control and asiaticoside treatment groups. We also found that asiaticoside could inhibit endoplasmic reticulum (ER) stress and pericyte apoptosis, which might be associated with the inhibition of junction protein reduction in ECs. Thus, we investigated the interactions between pericytes and ECs. Our results showed that asiaticoside could decrease the release of matrix metalloproteinase (MMP)-9 in pericytes and therefore upregulate the expression of junction proteins in ECs. Furthermore, the protective effect of asiaticoside on pericytes is related to the inhibition of ER stress via the MAPK signaling pathway. Taken together, our results demonstrate that asiaticoside treatment inhibits BSCB disruption and enhances functional recovery after SCI.

Biomechanical stability of oblique lateral interbody fusion combined with four types of internal fixations: finite element analysis.

Objective: Using finite element analysis to identify the optimal internal fixation method for oblique lateral lumbar interbody fusion (OLIF), providing guidance for clinical practice. Methods: A finite element model of the L4 - L5 segment was created. Five types of internal fixations were simulated in the generated L4-L5 finite element (FE) model. Then, six loading scenarios, i.e., flexion, extension, left-leaning, right-leaning, rotate left, and rotate right, were simulated in the FE models with different types of fixations. The biomechanical stability of the spinal segment after different fixations was investigated. Results: Regarding the range of motion (ROM) of the fused segment, OLIF + Bilateral Pedicle Screws (BPS) has a maximum ROM of 1.82° during backward bending and the smallest ROM in all directions of motion compared with other models. In terms of the von Mises stress distribution on the cage, the average stress on every motion direction of OLIF + BPS is about 17.08MPa, and of OLIF + Unilateral Vertebral Screw - Pedicle Screw (UVS-PS) is about 19.29 MPa. As for the von Mises stress distribution on the internal fixation, OLIF + BPS has the maximum internal fixator stress in left rotation (31.85 MPa) and OLIF + Unilateral Pedicle Screw (UPS) has the maximum internal fixator stress in posterior extension (76.59 MPa). The data of these two models were smaller than those of other models. Conclusion: OLIF + BPS provides the greatest biomechanical stability, OLIF + UPS has adequate biomechanical stability, OLIF + UVS-PS is inferior to OLIF + UPS synthetically, and OLIF + Double row vertical screw (DRVS) and Individual OLIF (IO) do not present significant obvious advantages.

Taxifolin attenuates neuroinflammation and microglial pyroptosis via the PI3K/Akt signaling pathway after spinal cord injury.

Spinal cord injury (SCI) is a severe injury characterized by neuroinflammation and oxidative stress. Taxifolin is exhibits anti-inflammatory and antioxidative activities in neurologic diseases. However, the roles and mechanisms of taxifolin in neuroinflammation and microglial pyroptosis after SCI remain unclear. The present study aims to investigate the effect of taxifolin on SCI and its potential underlying mechanisms in in vivo and in vitro models. In this study, taxifolin markedly reduced microglial activation mediated oxidative stress, and inhibited the expression of pyroptosis-related proteins (NLRP3, GSDMD, ASC, and Caspase-1) and inflammatory cytokines (IL-1ß and IL-18) after SCI, as shown by immunofluorescence staining and western blot assays. In addition, taxifolin promoted axonal regeneration and improved functional recovery after SCI. In vitro studies showed that taxifolin attenuated the activation of microglia and oxidative stress after lipopolysaccharide (LPS) + adenosine-triphosphate (ATP) stimulation in BV2 cells. We also observed that taxifolin inhibited the pyroptosis-related proteins and reduced the release of inflammatory cytokines. Moreover, to explore how taxifolin exerts its effects on microglial pyroptosis and axonal regeneration of neurons, we performed an in vitro study in BV-2 cells and PC12 cells co-culture. The results revealed that taxifolin facilitated axonal regeneration of PC12 cells in co-culture with LPS + ATP-induced BV-2 cells. Mechanistically, taxifolin regulated microglial pyroptosis via the PI3K/AKT signaling pathway. Taken together, these results suggest that taxifolin alleviates neuroinflammation and microglial pyroptosis through the PI3K/AKT signaling pathway after SCI, and promotes axonal regeneration and improves functional recovery, suggesting that taxifolin may represent a potential therapeutic agent for SCI.