ABSTRACT
Repairing the human brain remains a challenge, despite the advances in the knowledge of inflammatory response to injuries and the discovery of adult neurogenesis. After brain injury, the hostile microenvironment and the lack of structural support for neural cell repopulation, anchoring, and synapse formation reduce successful repair chances. In the past decade, we witnessed the rise of studies regarding bioscaffolds' use as support for neuro repair. A variety of natural and synthetic materials is available and have been used to replace damaged tissue. Bioscaffolds can assume different shapes and may or may not carry a diversity of content, such as stem cells, growth factors, exosomes, and si/miRNA that promote specific therapeutic effects and stimulate brain repair. The use of these external bioscaffolds and the creation of cell platforms provide the basis for tissue engineering. More recently, researchers were able to engineer brain organoids, neural networks, and even 3D printed neural tissue. The challenge in neural tissue engineering remains in the fabrication of scaffolds with precisely controlled topography and biochemical cues capable of directing and controlling neuronal cell fate. The purpose of this review is to highlight the existing research in the growing field of bioscaffolds' development and neural tissue engineering. Moreover, this review also draws attention to emerging possibilities and prospects in this field.
ABSTRACT
Stem cell transplantation is a promising strategy to treat brain injuries. However, cell-based therapies are limited because poor local cell engraftment. Here, we present a polylactic acid (PLA) scaffold to support mesenchymal stem cells (MSCs) delivery in stroke. We isolated bone marrow MSCs from adult C57/Bl6 mice, cultured them on PLA polymeric rough microfibrous (PRM) scaffolds obtained by rotary jet spinning, and transplanted over the brains of adult C57/Bl6 mice, carrying thermocoagulation-induced cortical stroke. No inflammatory response to PRM was found. MSCs transplantation significantly reduced the area of the lesion and PRM delivery increased MSCs retention at the injury site. In addition, PRM upregulated α6-integrin and CXCL12 production, which may be the cause for greater cell retention at the lesion site and may provide additional benefit to MSCs transplantation procedures. We conclude that PRM scaffolds offer a promising new system to deliver stem cells to injured areas of the brain.
Subject(s)
Cell- and Tissue-Based Therapy/methods , Drug Delivery Systems , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Nanofibers/chemistry , Tissue Scaffolds/chemistry , Trauma, Nervous System/therapy , Animals , Bone Marrow Cells/cytology , Cell Differentiation , Female , Mice , Mice, Inbred C57BL , Tissue EngineeringABSTRACT
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
Subject(s)
Cell Movement/drug effects , Chondroitin Sulfates/pharmacology , Neural Stem Cells/cytology , Neural Stem Cells/enzymology , rho-Associated Kinases/metabolism , Animals , Cell Adhesion/drug effects , Cell Surface Extensions/drug effects , Cell Surface Extensions/metabolism , Cells, Cultured , Doublecortin Protein , Enzyme Activation/drug effects , Male , Mice, Inbred C57BL , Neural Stem Cells/drug effects , rho-Associated Kinases/antagonists & inhibitors , rhoA GTP-Binding Protein/metabolismABSTRACT
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
ABSTRACT
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate in vitro with neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired cell migration in vitro induced the formation of large mature adhesions and altered cell protrusion dynamics. ROCK inhibition restored migration in vitro as well as decreased adhesion size.
