Highlights d Mechanical tension-induced Yap activation triggers hepatocyte dedifferentiation d Confinement of cell spreading is sufficient to inhibit hepatocyte dedifferentiation d A chemical cocktail, LBDXL, maintains hepatocyte functions by targeting stress fibers d LBDXL hepatocytes resemble primary hepatocytes in gene expression and functions
Background: There is still no definite consensus on whether arthroscopic repair shows superiority over open repair for chronic lateral ankle instability. We conducted a systematic review and meta-analysis of the current comparative studies to make a generalized analysis. Methods: PubMed, Embase, and Web of Science databases were searched from inception to April 2020. Included studies were assessed by the level of evidence and quality of evidence (Cochrane Handbook or MINORS). The process of data extraction was conducted by two independent authors. The comparative results of clinical outcomes, stress radiographic outcomes, and complication rates between two groups were pooled. Statistical analysis was performed using STATA. Results: Nine comparative studies for a total of 473 patients (250 arthroscopic repair, 223 open repair) were included. For the clinical outcomes, a significant difference was found in favor of arthroscopic repair with regard to AOFAS scores (MD 0.32, 95% CI 0.12 to 0.53, I 2 = 7.7%, P = .370) and VAS scores (MD − 0.30, 95% CI − 0.54 to − 0.05, I 2 = 48.3%, P = .102). No significant difference was found regarding to stress radiographic outcomes. Importantly, the total complication rate (RR 0.88, 95% CI 0.51 to 1.49, I 2 = 0%, P = .957) as well as nerve complication rate (RR 1.21, 95% CI 0.53 to 2.75, I 2 = 0%, P = .975) of arthroscopic repair group is not significantly different to that of open repair group. Conclusions: Arthroscopic repair for lateral ankle instability shows excellent clinical results comparable to open repair. Especially, arthroscopic repair might alleviate more pain due to the minimally invasive procedure. Patients receiving arthroscopic repair do not result in a higher total complication rate and nerve injury rate.
Articular cartilage is highly specific and has limited capacity for regeneration if damaged. Human pluripotent stem cells (hPSCs) have the potential to generate any cell type in the body. Here, we report the dual-phase induction of ectodermal chondrogenic cells (ECCs) from hPSCs through the neural crest (NC). ECCs were able to self-renew long-term (over numerous passages) in a cocktail of growth factors and small molecules. The cells stably expressed cranial neural crest-derived mandibular condylar cartilage markers, such as MSX1, FOXC1 and FOXC2. Compared with chondroprogenitors from iPSCs via the paraxial mesoderm, ECCs had single-cell transcriptome profiles similar to condylar chondrocytes. After the removal of the cocktail sustaining self-renewal, the cells stopped proliferating and differentiated into a homogenous chondrocyte population. Remarkably, after transplantation, this cell lineage was able to form cartilage-like structures resembling mandibular condylar cartilage in vivo. This finding provides a framework to generate self-renewing cranial chondrogenic progenitors, which could be useful for developing cell-based therapy for cranial cartilage injury.
Myelin sheaths are essential in maintaining the integrity of axons. Development of the platform for in vitro myelination would be especially useful for demyelinating disease modeling and drug screening. In this study, a fiber scaffold with a core–shell structure was prepared in one step by the coaxial electrospinning method. A high-molecular-weight polymer poly-L-lactic acid (PLLA) was used as the core, while the shell was a natural polymer material such as hyaluronic acid (HA), sodium alginate (SA), or chitosan (CS). The morphology, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), contact angle, viability assay, and in vitro myelination by oligodendrocytes were characterized. The results showed that such fibers are bead-free and continuous, with an average size from 294 ± 53 to 390 ± 54 nm. The DSC and FTIR curves indicated no changes in the phase state of coaxial brackets. Hyaluronic acid/PLLA coaxial fibers had the minimum contact angle (53.1° ± 0.24°). Myelin sheaths were wrapped around a coaxial electrospun scaffold modified with water-soluble materials after a 14-day incubation. All results suggest that such a scaffold prepared by coaxial electrospinning potentially provides a novel platform for oligodendrocyte myelination.
Spinal cord impairment involving motor neuron degeneration and demyelination can cause life-long disabilities, but effective clinical interventions for restoring neurological functions have yet been developed. In early spinal cord development, neural progenitors in the pMN (‘progenitors of motor neurons’) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on the chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.
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