Epithelial‑mesenchymal transition (EMT) is a critical step in order for epithelial‑derived malignancies to metastasize, however, its role in mesenchymal‑derived tumors, i.e., osteosarcoma, remains unclear. Cancer stem cells (CSCs) are enriched with cells that undergo EMT. The activity of telomerase is maintained in normal stem cells and a number of malignant tumors. The current study observed the heterogeneity of telomerase activity among individual osteosarcoma cells. We hypothesized that telomerase‑positive (TELpos) cells are enriched for stem cell‑like and EMT properties. A human telomerase reverse transcriptase (hTERT) promoter‑reporter was applied to assess the telomerase activity of individual MG63 osteosarcoma cells and sort them into TELpos and telomerase‑negative (TELneg) subpopulations. It was found that the TELpos cells exhibited an enhanced ability to form sarcospheres in vitro. In addition, TELpos cells exhibited a higher expression of vimentin, accompanied by an increased long/short axis ratio. A panel of EMT‑related genes was evaluated by quantitative PCR and western blot analysis, and were found to be significantly upregulated in TELpos cells. Next, the in vitro migration capacity was examined by Transwell assay, which confirmed that TELpos cells are more prone to migration (2.6 fold). The results of the present study support the concept that EMT also applies to mesenchymal‑derived osteosarcoma and draws a connection between telomerase and EMT characteristics.
Stem cell cardiac patches have shown promising future for myocardium infarction (MI) therapy, but the characteristics of cardiac pulsation and tissue orientation lead to challenges in the design of cardiac repair scaffolds. Herein, a novel and multifunctional stem cell patch with favorable mechanical properties was reported. In this study, the scaffold was prepared by coaxial electrospinning of poly (CL-co-TOSUO)/collagen (PCT/collagen) core/shell nanofibers. Rat bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffold to prepare the MSC patch. The nanofiber diameter of coaxial PCT/collagen was 945 ± 102 nm, and the tensile testing results showed that the PCT/collagen core/shell nanofibers possess highly elastic mechanical properties with an elongation at break higher than 300%. The results also showed that the MSCs maintained stem cell properties following seeding on the nano-fibers. The cells on the transplanted MSC patch survived 15 ± 4% 5 weeks following transplantation, and this PCT/collagen-MSC patch significantly improved the MI cardiac function and promoted angiogenesis. With high elasticity and good stem cell biocompatibility, the PCT/collagen core/shell nanofibers exhibited a good research value in the field of myocardial patches.
Current approaches in myocardial infarction treatment are limited by low cellular oxidative stress resistance, reducing the long-term survival of therapeutic cells. Here we develop a liquid-crystal substrate with unique surface properties and mechanical responsiveness to produce size-controllable cardiospheres that undergo pyroptosis to improve cellular bioactivities and resistance to oxidative stress. We perform RNA sequencing and study cell metabolism to reveal increased metabolic levels and improved mitochondrial function in the preconditioned cardiospheres. We test therapeutic outcomes in a rat model of myocardial infarction to show that cardiospheres improve long-term cardiac function, promote angiogenesis and reduce cardiac remodeling during the 3-month observation. Overall, this study presents a promising and effective system for preparing a large quantity of functional cardiospheres, showcasing potential for clinical application.
2 July 2023 in Bioengineering & Translational Medicine
Recovery of skin function remains a significant clinical challenge for deep burns owing to the severe scar formation and poor appendage regeneration, and stem cell therapy has shown great potential for injured tissue regeneration. Here, a cell‐free therapy system for deep burn skin was explored using mesenchymal stem cell paracrine proteins (MSC‐PP) and polyethylene glycol (PEG) temperature‐sensitive hydrogels. A three‐dimensional (3D) dynamic culture system for MSCs' large‐scale expansion was established using a porous gelatin microcarrier crosslinked with hyaluronic acid (PGM‐HA), and the purified MSC‐PP from culture supernatant was characterized by mass spectrometric analysis. The results showed the 3D dynamic culture system regulated MSCs cell cycle, reduced apoptosis, and decreased lactic acid content, and the MSC‐PP produced in 3D group can promote cell proliferation, migration, and adhesion. The MSC‐PP + PEG system maintained stable release in 28 days of observation in vitro. The in vivo therapeutic efficacy was investigated in the rabbit's third‐degree burn model, and saline, PEG, MSC‐PP, and MSC‐PP + PEG treatments groups were set. The in vivo results showed that the MSC‐PP + PEG group significantly improved wound healing, inhibited scar formation, and facilitated skin appendage regeneration. In conclusion, the MSC‐PP + PEG sustained‐release system provides a potentially effective treatment for deep burn skin healing.
19 October 2022 in Materials Science and Engineering: C