Disassembly and Mislocalization of AQP4 in Incipient Scar Formation After Experimental Stroke

There is an urgent need to better understand the mechanisms involved in scar formation in brain. It is well known that astrocytes are critically engaged in this process. Here we analyze in-cipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mo-bility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.

Tissue Stromal Vascular Fraction Improves Early Scar Healing: A Prospective Randomized Multicenter Clinical Trial

Background Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. Tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. Objectives In this study, we hypothesized that tSVF reduces post-surgical scar formation. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of one breast and a placebo injection in the contralateral breast to serve as an intra-patient control. Primary outcome was scar quality using the patient and observer scar assessment scale (POSAS). Secondary outcomes were obtained with photograph evaluation and histological analysis of scar tissue samples. Results Thirty-four of 40 patients completed follow-up. Six months postoperatively, injection of tSVF had significantly improved postoperative scar appearance as assessed by POSAS questionnaire (observer and patient questionnaire). No difference was observed at 12 months postoperatively. No improvement was seen based on the evaluation of photographs and histological analysis of postoperative scars between both groups. Conclusions Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperative, without any noticeable advantageous effects seen at 12 months.

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

Adult regeneration in spinal cord is poor in mammalian but remarkable in the neonatal mammals and some vertebrates, including fish and salamanders. Increasing evidences basis of this interspecies and ontogeny highlighted the pivotal roles of neuron extrinsic factors-the glial scar, which exert confusing inhibiting or promoting regeneration function, but the spatiotemporal ordering of cellular and molecular events that drive repair processes in scar formation remains poorly understood. Here, we firstly constructed tissue-wide gene expression measurements of mouse spinal cords over the course of scar formation using the spatial transcriptomics (ST) technology in Spinal cord injury (SCI) repair. We analyzed the transcriptomes of nearly 15449 spots from 32 samples and distinguished normal and damage response regions. Compared to histological changes, spatial mapping of differentiation transitions in spinal cord injury site delineated the possible trajectory between subpopulations of fibroblast, glia and immune cell more comprehensively and defined the extent of scar boundary and core more accurately. Locally, we identified gene expression gradients from leading edge to the core of scar areas that allow for re-understanding of the scar microenvironment and found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophage, CD36 and Postn in fibroblast, Plxnb2 and Nxpe3 in microglia, Clu in astrocyte and CD74 in oligodendrocyte. Last, we profiled the bidirectional ligand-receptor interactions at the neighbor cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found GPR37L1_PSAP and GPR37_PSAP were top 2 enriched gene-pairs between microglia and fibroblast or microglia and astrocyte. Together, the establishment of these profiles firstly uncovered scar spatial heterogeneity and lineage trajectory, provide an unbiased view of scar and served as a valuable resource for CNS injury treatment.

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar

Transected axons are unable to regenerate after spinal cord injury (SCI). Glial scar is thought to be responsible for this failure. Regulating the formation of glial scar post-SCI may contribute to axonal regrow. Over the past few decades, studies have found that the interaction between immune cells at the damaged site results in a robust and persistent inflammatory response. Current therapy strategies focus primarily on the inhibition of subacute and chronic neuroinflammation after the acute inflammatory response was executed. Growing evidences have documented that mesenchymal stem cells (MSCs) engraftment can be served as a promising cell therapy for SCI. Numerous studies have shown that MSCs transplantation can inhibit the excessive glial scar formation as well as inflammatory response, thereby facilitating the anatomical and functional recovery. Here, we will review the effects of inflammatory response and glial scar formation in spinal cord injury and repair. The role of MSCs in regulating neuroinflammation and glial scar formation after SCI will be reviewed as well.