GDNF-Loaded Polydopamine Nanoparticles-Based Anisotropic Scaffolds Promote Spinal Cord Repair by Modulating Inhibitory Microenvironment.

Spinal cord injury (SCI) is a devastating injury that causes permanent loss of sensation and motor function. SCI repair is a significant challenge due to the limited regenerating ability of adult neurons and the complex inflammatory microenvironment. After SCI, the oxidative stress induced by excessive reactive oxygen species (ROS) often leads to prolonged neuroinflammation that results in sustained damage to the spinal cord tissue. Polydopamine (PDA) shows remarkable capability in scavenging ROS to treat numerous inflammatory diseases. In this study, glial cell-derived neurotrophic factor (GDNF)-loaded PDA nanoparticle-based anisotropic scaffolds for spinal cord repair are developed. It is found that mesoporous PDA nanoparticles (mPDA NPs) in the scaffolds efficiently scavenge ROS and promote microglia M2 polarization, thereby inhibiting inflammatory response at the injury site and providing a favorable microenvironment for nerve cell survival. Furthermore, the GDNF encapsulated in mPDA NPs promotes corticospinal tract motor axon regeneration and its locomotor functional recovery. Together, findings from this study reveal that the GDNF-loaded PDA/Gelatin scaffolds hold potential as an effective artificial transplantation material for SCI treatment.

Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects.

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.