The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury.

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system. Following surgery, the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality. Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord. Consequently, there is a critical need to develop new treatments to promote functional repair after spinal cord injury. Over recent years, there have been several developments in the use of stem cell therapy for the treatment of spinal cord injury. Alongside significant developments in the field of tissue engineering, three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures. This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization. These three-dimensional bioprinting scaffolds could repair damaged neural circuits and had the potential to repair the damaged spinal cord. In this review, we discuss the mechanisms underlying simple stem cell therapy, the application of different types of stem cells for the treatment of spinal cord injury, and the different manufacturing methods for three-dimensional bioprinting scaffolds. In particular, we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

Exosomes combined with biomaterials in the treatment of spinal cord injury.

Spinal cord injury (SCI) is a serious and disabling disease with a high mortality rate. It often leads to complete or partial sensory and motor dysfunction and is accompanied by a series of secondary outcomes, such as pressure sores, pulmonary infections, deep vein thrombosis in the lower extremities, urinary tract infections, and autonomic dysfunction. Currently, the main treatments for SCI include surgical decompression, drug therapy, and postoperative rehabilitation. Studies have shown that cell therapy plays a beneficial role in the treatment of SCI. Nonetheless, there is controversy regarding the therapeutic effect of cell transplantation in SCI models. Meanwhile exosomes, as a new therapeutic medium for regenerative medicine, possess the advantages of small size, low immunogenicity, and the ability to cross the blood-spinal cord barrier. Certain studies have shown that stem cell-derived exosomes have anti-inflammatory effects and can play an irreplaceable role in the treatment of SCI. In this case, it is difficult for a single treatment method to play an effective role in the repair of neural tissue after SCI. The combination of biomaterial scaffolds and exosomes can better transfer and fix exosomes to the injury site and improve their survival rate. This paper first reviews the current research status of stem cell-derived exosomes and biomaterial scaffolds in the treatment of SCI respectively, and then describes the application of exosomes combined with biomaterial scaffolds in the treatment of SCI, as well as the challenges and prospects.

Construction of a decellularized spinal cord matrix/GelMA composite scaffold and its effects on neuronal differentiation of neural stem cells.

Spinal cord injury (SCI) leads to severe loss of motor and sensory functions, and the rehabilitation of SCI is a worldwide problem. Tissue-engineered scaffolds offer new hope for SCI patients, while the newly developed materials encountered a challenge in modeling the microenvironment around the lesion site. We constructed a new composite scaffold by mixing decellularized spinal cord extracellular matrix (dECM) with gelatin methacryloyl (GelMA). The dECM, as a natural biological material, retained a large number of proteins and growth factors related to neurogenesis. GelMA was a photopolymerizable material, harbored a polymer network structure, soft texture, certain shape and plenty of water. The viability, proliferation, and differentiation of neural stem cells (NSCs) on the composite scaffold were evaluated by cell count kit-8 (CCK8), Live/Dead assay, phalloidin staining, 5-Ethynyl-2'-deoxyurdine (EdU), immunofluorescence staining and western blot. The Live/Dead assay, phalloidin staining, EdU, and CCK8 assay showed that the composite scaffold had good biocompatibility and provided better support for proliferation of NSCs. Results of immunocytochemistry and western blot showed that the composite scaffolds promoted the specific differentiation of NSCs into neuron cells. Together, this dECM/GelMA composite scaffold can be used as a cell culture coating, the isolated NSCs seeded on the surface of composite scaffold expressed neuronal markers and assumed neuronal morphology. Our work provided a new method that would be widely used in tissue engineering of SCI.

A decellularized spinal cord extracellular matrix-gel/GelMA hydrogel three-dimensional composite scaffold promotes recovery from spinal cord injury via synergism with human menstrual blood-derived stem cells.

Spinal cord injury (SCI), as a serious disabling disease, is still haunted by lacking of effective treatments. We previously found that transplantation of menstrual blood-derived mesenchymal stem cells (MenSCs) promoted axon regeneration in rats with SCI, while the abominable microenvironment after the SCI inhibited the survival of stem cells after transplantation. Biomaterials can support the activity of stem cells and accelerate the functional reconstruction of the injured spinal cord. In this study, we constructed a novel composite scaffold consisting of the decellularized spinal cord extracellular matrix-gel (DSCG) and the GelMA hydrogel, which harbored high water retention, wettability, degradability and soft mechanical property. In vitro, the DSCG/GelMA composite scaffold provided a dual bionic microenvironment with optimized bioactive components and favorable microstructures for the adhesion, proliferation and differentiation of MenSCs. After that, we prepared MenSC-encapsulated DSCG/GelMA composite scaffolds to bridge the 2 mm gap in rats with completely transected SCI. The in vivo results showed that the combined use of the DSCG/GelMA composite scaffold with MenSCs improved the motor function, reduced the inflammatory response, promoted neuronal differentiation, and inhibited the proliferation of reactive astrocytes after spinal cord injury. Altogether, our study provided a promising novel therapeutic option of using bioactive materials synergistic with stem cells for the treatment of SCI.

Cancer Treatment Evolution from Traditional Methods to Stem Cells and Gene Therapy.

BACKGROUND: Cancer, a malignant tumor, is caused by the failure of the mechanism that controls cell growth and proliferation. Late clinical symptoms often manifest as lumps, pain, ulcers, and bleeding. Systemic symptoms include weight loss, fatigue, and loss of appetite. It is a major disease that threatens human life and health. How to treat cancer is a long-standing problem that needs to be overcome in the history of medicine. METHODS: Traditional tumor treatment methods are poorly targeted, and the side effects of treatment seriously damage the physical and mental health of patients. In recent years, with the advancement of medical science and technology, the research on gene combined with mesenchymal stem cells to treat tumors has been intensified. Mesenchymal stem cells carry genes to target cancer cells, which can achieve better therapeutic effects. DISCUSSION: In this study, we systematically review the cancer treatment evolution from traditional methods to novel approaches that include immunotherapy, nanotherapy, stem cell theapy, and gene therapy. We provide the latest review of the application status, clinical trials, and development prospects of mesenchymal stem cells and gene therapy for cancer, as well as their integration in cancer treatment. Mesenchymal stem cells are effective carriers carrying genes and provide new clinical ideas for tumor treatment. CONCLUSION: This review focuses on the current status, application prospects, and challenges of mesenchymal stem cell combined gene therapy for cancer and provides new ideas for clinical research.