Saijilafu

Retinal organoids (ROs) are three-dimensional in vitro models that replicate the specific cellular composition and inner structure of the retina. Currently, ROs derived from human pluripotent stem cells (hPSCs) have been shown to mimic both the structure and function of the human retina. Furthermore, ROs function as a powerful model system for researchers, facilitating the investigation of the pathogenesis and treatment strategies of retinal diseases. Despite their development for over a decade, ROs remain limited in terms of complexity and clinical application. This review summarizes recent advances in the development of retinal differentiation methods and underscores their potential applications in disease modeling, gene therapy, cell transplantation, and drug screening. In addition, it proposes research directions that are geared towards advancing RO methodologies to further broaden their applications.

Axon regrowth is a key determinant of the restoration of the biological function of the nervous system after trauma. However, mature mammalian neurons have limited capacity for axon regeneration. We have previously demonstrated that neuronal axon growth both in the central and the peripheral nervous systems is markedly enhanced when non-muscle myosin II (NMII) is inhibited with blebbistatin. The activity of NMII is primarily regulated by MLCK and MLCP via the phosphorylation and dephosphorylation of its light chain, respectively; however, the functional roles of MLCK and MLCP in mammalian axonal regeneration remain unknown. In the present study, we provide strong evidence that the inhibition of MLCK activity significantly blocks axon regeneration in mice. Conversely, the inhibition of MLCP promotes axon regrowth of both the peripheral and central nervous system. Our findings further indicate that the MLCK/MLCP regulates axon regeneration and redistributes the growth cone F-actin, and this result suggests that direct regulation of the growth cone machinery is a potential strategy to promote axon regeneration.

Spinal cord injury (SCI) is a very destructive disease of the central nervous system that often causes irreversible nerve damage. Unfortunately, the adult mammalian spinal cord displays little regenerative capacity after injury. In addition, the glial scars and inflammatory responses around the lesion site are another major obstacle for successful axon regeneration after SCI. However, biomaterials are highly biocompatible, and they could provide physical guidance to allow regenerating axon growth over the lesion site and restore functional neural circuits. In addition, combined or synergistic effects of spinal cord repair can be achieved by integrating different strategies, including the use of various biomaterials and microstructures, as well as combining bioactive molecules and living cells. Therefore, it is possible to use tissue engineering scaffolds to regulate the local microenvironment of the injured spinal cord, which may achieve better functional recovery in spinal cord injury repair. In this review, we summarize the latest progress in the treatment of SCI by biomaterials, and discussed its potential mechanism.

Introduction: Cycloastragenol (CAG) has a wide range of pharmacological effects, including anti-inflammatory, antiaging, antioxidative, and antitumorigenic properties. In addition, our previous study showed that CAG administration can promote axonal regeneration in peripheral neurons. However, whether CAG can activate axon regeneration central nervous system (CNS) remains unknown.Methods: Here, we established a novel mouse model for visualizing spinal cord dorsal column axon regeneration involving the injection of AAV2/9-Cre into the lumbar 4/5 dorsal root ganglion (DRG) of Rosa-tdTomato reporter mice. We then treated mice by intraperitoneal administration of CAG.Results: Our results showed that intraperitoneal CAG injections significantly promoted the growth of vitro-cultured DRG axons as well as the growth of dorsal column axons over the injury site in spinal cord injury (SCI) mice. Our results further indicate that CAG administration can promote the recovery of sensory and urinary function in SCI mice.Conclusion: Together, our findings highlight the therapeutic potential of CAG in spinal cord injury repair.

Axon regrowth is a key determinant of the restoration of the biological function of the nervous system after trauma. However, mature mammalian neurons have limited capacity for axon regeneration. We have previously demonstrated that neuronal axon growth both in the central and the peripheral nervous systems is markedly enhanced when non-muscle myosin II (NMII) is inhibited with blebbistatin. The activity of NMII is primarily regulated by MLCK and MLCP via the phosphorylation and dephosphorylation of its light chain, respectively; however, the functional roles of MLCK and MLCP in mammalian axonal regeneration remain unknown. In the present study, we provide strong evidence that the inhibition of MLCK activity significantly blocks axon regeneration in mice. Conversely, the inhibition of MLCP promotes axon regrowth of both the peripheral and central nervous system. Our findings further indicate that the MLCK/MLCP regulates axon regeneration and redistributes the growth cone F-actin, and this result suggests that direct regulation of the growth cone machinery is a potential strategy to promote axon regeneration.

Purpose/Aim: Bone defects caused by trauma, tumors, congenital malformation, or inflammation are very common in orthopedics. In recent years, mimicking the composition and structure of natural bone tissue has become a hot topic in biomaterial research, with the aim of developing an ideal biomaterial for bone defect transplantation. Here, the feasibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel to repair bone defects was evaluated in vitro and in rats. Materials and Methods: Results: The BCP/GelMA composite hydrogel displayed excellent biocompatibility and promoted osteogenesis of bone marrow mesenchymal stem cells in vitro. In addition, the BCP/GelMA composite hydrogel markedly promoted new bone formation in the rat skull-defect model. Conclusions: BCP/GelMA composite hydrogel may be an effective artificial material for bone tissue engineering.

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.

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.

Because of the limited regenerative ability of the central nervous system (CNS), effective treatments for spinal cord injury (SCI) are still lacking. After SCI, neuron loss and axon regeneration failure often result in irreversible functional impairment. The calcium overload induced by the N‐methyl‐D‐aspartate receptor (NMDAR) overactivation is critical for cell death in SCI. It has been reported that the magnesium ion (Mg²⁺) can competitively block the NMDAR and reduce the calcium influx, and that sonic hedgehog (Shh) and retinoic acid (RA) are the critical regulators of neuronal differentiation of endogenous neural stem cells (NSCs). Here, magnesium oxide (MgO)/poly (l‐lactide‐co‐ε‐caprolactone) (PLCL) scaffold loaded with purmorphamine (PUR, a Shh signaling agonist) and RA is developed and its feasibility in SCI repair is tested. The results showed that the Mg²⁺ released from MgO attenuated cell apoptosis by blocking the calcium influx, and the PUR/RA promoted the recruitment and neuronal differentiation of endogenous NSCs, thereby reducing the glial scar formation at the SCI lesion site. Furthermore, implantation of PUR/RA‐loaded MgO/PLCL scaffold facilitates the partial recovery of a locomotor function of SCI mouse in vivo. Together, findings from this study imply that PUR/RA‐loaded MgO/PLCL scaffold may be a promising biomaterial for the clinical treatment of SCI.

The loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo , and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.