Implanted neural stem cell grafts show functionality in spinal cord injuries

In mouse studies, the specialized grafts integrated with host networks and behaved much like neurons in a healthy, undamaged spinal cord. Using stem cells to restore lost functions due to spinal cord injury (SCI) has long been an ambition of scientists and doctors. In a new study, published Aug. 5, 2020, in Cell Stem Cell, researchers at University of California San Diego School of Medicine report successfully implanting highly specialized grafts of neural stem cells directly into spinal cord injuries in mice, then documenting how the grafts grew and filled the injury sites, integrating with and mimicking the animals' existing neuronal network. Until this study, said the study's first author Steven Ceto, a postdoctoral fellow in the lab of Mark Tuszynski, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, neural stem cell grafts being developed in the lab were sort of a black box. The researchers took advantage of recent technological advances that allow researchers to both stimulate and record the activity of genetically and anatomically defined neuron populations with light rather than electricity. This ensured they knew exactly which host and graft neurons were in play, without having to worry about electric currents spreading through tissue and giving potentially misleading results. They discovered that even in the absence of a specific stimulus, graft neurons fired spontaneously in distinct clusters of neurons with highly correlated activity, much like in the neural networks of the normal spinal cord. When researchers stimulated regenerating axons coming from the animals' brain, they found that some of the same spontaneously active clusters of graft neurons responded robustly, indicating that these networks receive functional synaptic connections from inputs that typically drive movement. Sensory stimuli, such as a light touch and pinch, also activated graft neurons.

Silk scaffolds and magnetism to generate bone tissue and be able to use it in implants

The journal Materialia has recently published the outcome of a piece of research conducted by a group of researchers comprising several from the Department of Physical Chemistry at the UPV-EHU's Faculty of Science and Technology and BCMaterials, and others from centers at the University of Minho (Portugal). In this work the research group developed a new composite material that can be used for tissue engineering, specifically for regenerating bone tissue. "The ultimate goal of this line of research would be to be able to generate tissue that could then be implanted to treat bone diseases," said José Luis Vilas-Vilela, head of the UPV/EHU's Department of Physical Chemistry and one of the authors of this study. The material developed comprises a scaffold or matrix which in turn is made up of one of the main components of silk (fibroin), a biocompatible material of natural origin, and which is loaded with magnetic nanoparticles. The purpose of adding the nanoparticles was to make the material "magnetoactive" so that they would respond when a magnetic field is applied to them and thus transmit mechanical and electrical stimuli to the cells. "The inserting of stimuli, which may be electrical, magnetic, mechanical or of another type, has been proven to encourage cell growth and differentiation, because this procedure in some way mimics the cellular microenvironment and imitates the stimuli that occur in the environment in which the cells carry out their functions," the researchers said.

Hydrogel paves way for biomedical breakthrough

Published in Advanced Functional Materials, a University of Sydney team of biomedical engineers has developed a plasma technology to robustly attach hydrogels – a jelly-like substance which is structurally similar to soft tissue in the human body – to polymeric materials, allowing manufactured devices to better interact with surrounding tissue. To function optimally in the body, a manufactured implant – whether it be an artificial hip, a fabricated spinal disc or engineered tissue – must bond and interact with appropriate surrounding tissues and living cells. When that doesn't happen, an implant may fail or, worse still, be rejected by the body. Worldwide, implant failures and rejections are a significant cost to health systems, placing large financial and health burdens on patients. Hydrogels are highly attractive for tissue engineering because of their functional and structural similarity to human body soft tissue," the researchers said. "Our group's unique plasma process, recently reported in ACS Applied Materials and Interfaces, enables us to activate all surfaces of complex, porous structures, such as scaffolds, to covalently attach biomolecules and hydrogels," said ARC Laureate and Biomedical Engineering academic, Marcela Bilek. "These advances enable the creation of mechanically robust complex-shaped polymeric scaffolds infused with hydrogel, bringing us a step closer to mimicking the characteristics of natural tissues within the body," Bilek added. Biomedical devices, organ implants, biosensors and tissue engineering scaffolds that are set to benefit from the new hydrogel technology. The researchers said the gel could be loaded with a drug to release slowly over time, or it can be used to mimic structures such as bone-cartilage. The researchers also noted that these materials are also excellent candidates for applications such as lab-on-a-chip platforms, bioreactors that mimic organs, and biomimetic constructs for tissue repair as well as antifouling coatings for surfaces submerged in marine environments.

New strategy against osteoporosis

In osteoporosis, disproportionate bone resorption leads to low bone mineral density and consequently weak and fracture-prone bones. When new bone formation is unable to catch up with bone loss, bone eventually weakens, and becomes more prone to fractures. Most current osteoporosis therapies include the use of bisphosphonates, which block the activity of bone resorbing cells, and thus prevent excessive bone resorption. However, prolonged treatment with these drugs eliminates the necessary bone turn-over leading to increased fracture risk and other unwanted side effects. Therefore, there is an urgent need to develop new strategies that overcome the limitations of current treatments. There are now new progresses in this area. They have been developed in a cooperation of Professors Christoph Winkler (Department of Biological Sciences, National University of Singapore, NUS) and Manfred Schartl (Biocenter, Julius-Maximilians-Universität Würzburg, JMU, Germany); the results have been published in the journal PNAS. Using genetic analysis in a small laboratory fish model, the Japanese medaka (Oryzias latipes), the research team identified a small protein, the chemokine CXCL9, that, under osteoporotic conditions, diffuses towards reservoirs that hold bone resorbing cell precursors. These precursors produce a receptor, CXCR3, on their cell surface. Upon activation by CXCL9, the precursors are mobilized and migrate long distances in a highly directed fashion towards the bone matrix, where they start resorbing bone. “The new strategy allows a fine-tuned modulation of osteoclast numbers that are recruited to bone matrix rather than a widespread blockage of osteoclast activity as in traditional therapies. This offers potential to avoid increased fracture risks in osteoporosis patients and to maintain healthy bone for improved quality of life,” the researchers said.

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