Background: Cell-based therapy using adipose-derived mesenchymal stem cells (ADSCs) is a promising treatment strategy for neurogenic bladder (NB) associated with spinal cord injury (SCI). However, therapeutic efficacy is low because of inefficient cell delivery. Cell sheets improve the efficacy of cell transplantation. Therefore, this study was conducted to investigate the therapeutic efficacy of transplanting ADSC sheets into an SCI rat model and focused on the function and pathological changes of the bladder. Methods: ADSC sheets were prepared from adipose tissue of Sprague–Dawley (SD) rats using temperature-responsive cell culture dishes. Adult female SD rats were subjected to SCI by transection at the T10 level and administered ADSC sheets or gelatin sponge (the control group). Four and 8 weeks later, in vivo cystometrograms were obtained for voiding function assessment. Rats were sacrificed and the expression of various markers was analyzed in spinal and bladder tissues. Results: The number of β-tubulin III-positive axons in the ADSC sheet transplantation group was higher than that in the control group. Conversely, expression of glial fibrillary acidic protein in the ADSC sheet transplantation group was lower than that in the control group. Cystometry showed impairment of the voiding function after SCI, which was improved after ADSC sheet transplantation with increased high-frequency oscillation activity. Furthermore, ADSC sheet transplantation prevented disruption of the bladder urothelium in SCI rats, thereby maintaining the intact barrier. Compared with fibrosis of the bladder wall in the control group, the ADSC sheet transplantation group had normal morphology of the bladder wall and reduced tissue fibrosis as shown by downregulation of type 1 collagen. ADSC sheet transplantation also resulted in strong upregulation of contractile smooth muscle cell (SMC) markers (α-smooth muscle actin and smoothelin) and downregulation of synthetic SMC markers (MYH10 and RBP1). Conclusion: ADSC sheet transplantation significantly improved voiding function recovery in rats after SCI. ADSC sheet transplantation is a promising cell delivery and treatment option for NB related to SCI.
3D bioprinting technology, a subset of 3D printing technology, is currently witnessing widespread utilization in tissue repair and regeneration endeavors. In particular, light-based 3D bioprinting technology has garnered significant interest and favor. Central to its successful implementation lies the judicious selection of photosensitive polymers. Moreover, by fine-tuning parameters such as light irradiation time, choice of photoinitiators and crosslinkers, and their concentrations, the properties of the scaffolds can be tailored to suit the specific requirements of the targeted tissue repair sites. In this comprehensive review, we provide an overview of commonly utilized bio-inks suitable for light-based 3D bioprinting, delving into the distinctive characteristics of each material. Furthermore, we delineate strategies for bio-ink selection tailored to diverse repair locations, alongside methods for optimizing printing parameters. Ultimately, we present a coherent synthesis aimed at enhancing the practical application of light-based 3D bioprinting technology in tissue engineering, while also addressing current challenges and future prospects.
Urethral stricture is a common urological disease that seriously affects quality of life. Urethroplasty with grafts is the primary treatment, but the autografts used in clinical practice have unavoidable disadvantages, which have contributed to the development of urethral tissue engineering. Using various types of seed cells in combination with biomaterials to construct a tissue-engineered urethra provides a new treatment method to repair long-segment urethral strictures. To date, various cell types have been explored and applied in the field of urethral regeneration. However, no optimal strategy for the source, selection, and application conditions of the cells is available. This review systematically summarizes the use of various cell types in urethral regeneration and their characteristics in recent years and discusses possible future directions of cell-based therapies.
The regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink, which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g., in vascularization, effective antibacterial, immunomodulation, and regulation of collagen deposition. Many studies incorporated different bioactive materials into the 3D-printed scaffolds to optimize the bioprinting. Here, we reviewed a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide a useful basis for future research.
In recent years, decellularized extracellular matrices (dECM) derived from organs have attracted much attention from researchers due to their excellent biocompatibility, capacity to promote cell proliferation and migration, as well as pro-vascularization. However, their inferior mechanical properties, slow cross-linking, weak strengths, and poor supporting properties remain their inevitable challenges. In our study, we fabricated a novel dECM hydrogel with better crosslinking strength and speed, stronger support properties, and better mechanical properties. The hydrogel, which we named gelatin-based dECM powder hydrogel (gelatin-dECM hydrogel), was prepared by mixing dECM microparticles in gelatin solution and adding certain amount of 1-Ethyl-3-(3-dimethyl-aminopropyl-1-carbodiimide) (EDC) and N-hydroxysuccinimide (NHS). We evaluated the utility of this hydrogel by assessing the degradation rate, mechanical properties, and biocompatibility. The results showed that the gelatin-dECM hydrogel has high mechanical properties and biocompatibility and also has the ability to promote cell proliferation and migration. After injection of this hydrogel around the surgical sites of urethras in rabbits, the incorporation of dECM powder was demonstrated to promote angiogenesis as well as scarless repair by histological sections after surgery. The application of this novel hydrogel provides a new perspective for the treatment of post-traumatic urethral stricture.
Background: Clear cell renal cell carcinoma (ccRCC) is the main subtype of renal cell carcinoma and has different prognoses, especially in patients with metastasis. Here, we aimed to establish a novel model to predict overall survival (OS) and surgical benefit of ccRCC patients with distant metastasis.Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) databases, we identified 2185 ccRCC patients with distant metastasis diagnosed from 2010 to 2015. Univariate and multivariate Cox analysis were used to identify significant prognostic clinicopathological variables. By integrating these variables, a prognostic nomogram was constructed and evaluated using C-indexes and calibration curves. The discriminative ability of the nomogram was measured by analyses of receiver operating characteristic (ROC) curve. A risk stratification model was built according to each patient's total scores. Kaplan-Meier curves were performed in the low-, intermediate- and high-risk groups to evaluate the survival benefit of surgery.Results: Eight clinicopathological variables were included as independent prognostic factors in the nomogram: grade, marital status, T stage, N stage, bone metastasis, brain metastasis, liver metastasis, and lung metastasis. The nomogram had a better discriminative ability for predicting OS than Tumor-Node-Metastasis (TNM) stage. The C-index was 0.71 (95% CI 0.68–0.74) in the training cohort. The calibration plots demonstrated that the nomogram-based predictive outcomes had good consistency with the actual prognosis results. Total nephrectomy improved prognosis in both the low-risk and intermediate-risk groups, but partial nephrectomy could only benefit the low-risk group.Conclusions: We constructed a predictive nomogram and risk stratification model to evaluate prognosis in ccRCC patients with distant metastasis, which was valuable for prognostic stratification and making therapeutic decisions.