Mesenchymal Stem Cell Transplantation: Neuroprotection and Nerve Regeneration After Spinal Cord Injury.

Spinal Cord Injury (SCI), with its morbidity characteristics of high disability rate and high mortality rate, is a disease that is highly destructive to both the physiology and psychology of the patient, and for which there is still a lack of effective treatment. Following spinal cord injury, a cascade of secondary injury reactions known as ischemia, peripheral inflammatory cell infiltration, oxidative stress, etc. create a microenvironment that is unfavorable to neural recovery and ultimately results in apoptosis and necrosis of neurons and glial cells. Mesenchymal stem cell (MSC) transplantation has emerged as a more promising therapeutic options in recent years. MSC can promote spinal cord injury repair through a variety of mechanisms, including immunomodulation, neuroprotection, and nerve regeneration, giving patients with spinal cord injury hope. In this paper, it is discussed the neuroprotection and nerve regeneration components of MSCs' therapeutic method for treating spinal cord injuries.

The role and mechanisms of mesenchymal stem cells regulating macrophage plasticity in spinal cord injury.

Spinal Cord Injury (SCI) is a devastating neurological disorder comprising primary mechanical injury and secondary inflammatory response-mediated injury for which an effective treatment is still unavailable. It is well known that secondary inflammatory responses are a significant cause of difficulties in neurological recovery. An immune imbalance between M1/M2 macrophages at the sites of injury is involved in developing and progressing the secondary inflammatory response. Recently, Mesenchymal Stem Cells (MSCs) have shown significant therapeutic potential in tissue engineering and regenerative medicine due to their potential multidirectional differentiation and immunomodulatory properties. Accumulating evidence shows that MSCs can regulate the balance of M1/M2 macrophage polarization, suppress downstream inflammatory responses, facilitate tissue repair and regeneration, and improve the prognosis of SCI. This article briefly overviews the impact of macrophages and MSCs on SCI and repair. It discusses the mechanisms by which MSCs regulate macrophage plasticity, including paracrine action, release of exosomes and apoptotic bodies, and metabolic reprogramming. Additionally, the article summarizes the relevant signaling pathways of MSCs that regulate macrophage polarization.

Mechanism of M2 macrophages modulating astrocyte polarization through the TGF-ß/PI3K/Akt pathway.

Recent studies have revealed that activated astrocytes (AS) are divided into two distinct types, termed A1 and A2. A2 astrocytes are neuroprotective and promote tissue repair and regeneration following spinal cord injury. Whereas, the specific mechanism for the formation of the A2 phenotype remains unclear. This study focused on the PI3K/Akt pathway and examined whether TGF-ß secreted by M2 macrophages could mediate A2 polarization by activating this pathway. In this study, we revealed that both M2 macrophages and their conditioned medium (M2-CM) could facilitate the secretion of IL-10, IL-13 and TGF-ß from AS, and this effect was significantly reversed after the administration of SB431542 (a TGF-ß receptor inhibitor) or LY294002 (a PI3K inhibitor). Moreover, immunofluorescence results demonstrated that TGF-ß secreted by M2 macrophages could facilitate the expression of A2 biomarker S100A10 in AS; combined with the results of western blot, it was found that this effect was closely related to the activation of PI3K/Akt pathway in AS. In conclusion, TGF-ß secreted by M2 macrophages may induce the conversion of AS to the A2 phenotype through the activation of the PI3K/Akt pathway.

Multiple strategies enhance the efficacy of MSCs transplantation for spinal cord injury.

Spinal cord injury (SCI) is a serious complication of the central nervous system (CNS) after spine injury, often resulting in severe sensory, motor, and autonomic dysfunction below the level of injury. To date, there is no effective treatment strategy for SCI. Recently, stem cell therapy has brought hope to patients with neurological diseases. Mesenchymal stem cells (MSCs) are considered to be the most promising source of cellular therapy after SCI due to their immunomodulatory, neuroprotective and angiogenic potential. Considering the limited therapeutic effect of MSCs due to the complex pathophysiological environment following SCI, this paper not only reviews the specific mechanism of MSCs to facilitate SCI repair, but also further discusses the research status of these pluripotent stem cells combined with other therapeutic approaches to promote anatomical and functional recovery post-SCI.

Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.

It is often difficult to regain neurological function following spinal cord injury (SCI). Neuroinflammation is thought to be responsible for this failure. Regulating the inflammatory response post-SCI may contribute to the recovery of neurological function. Over the past few decades, studies have found that macrophages/microglia are one of the primary effector cells in the inflammatory response following SCI. Growing evidence has documented that macrophages/microglia are plastic cells that can polarize in response to microenvironmental signals into M1 and M2 macrophages/microglia. M1 produces pro-inflammatory cytokines to induce inflammation and worsen tissue damage, while M2 has anti-inflammatory activities in wound healing and tissue regeneration. Recent studies have indicated that the transition from the M1 to the M2 phenotype of macrophage/microglia supports the regression of inflammation and tissue repair. Here, we will review the role of the inflammatory response and macrophages/microglia in SCI and repair. In addition, we will discuss potential molecular mechanisms that induce macrophage/microglia polarization, with emphasis on neuroprotective therapies that modulate macrophage/microglia polarization, which will provide new insights into therapeutic strategies for SCI.