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Pioneering studies conducted in the 1980’s laid the foundation for the hypothesis that axonal regeneration is limited by CNS myelin, and the identification of myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein (OMgp) as inhibitors of neurite outgrowth firmly established myelin as a key factor in regenerative failure. Mechanistically, it has been shown that MAG, Nogo, and OMgp mediate inhibition by binding to either Nogo receptor (NgR) or paired immunoglobulin receptor B (PirB), and initiating a signaling cascade that culminates in the activation of RhoA. Since the discovery of these proteins, there has been tremendous interest in identifying compounds and molecular mechanisms that are capable of overcoming myelin-mediated inhibition. Many studies have focused on pharmacological antagonism of receptors and signaling intermediates, while others have sought to identify and enhance endogenous pro-regenerative pathways. The most notable example of the latter is the conditioning lesion effect, which led to the discovery of cyclic AMP’s ability to overcome inhibition by MAG and myelin. Many of the agents tested in these studies have been shown to promote axonal regeneration in vivo, and this research topic allows researchers to share information about new treatments that have been developed in both academia and industry. As we look toward the future, it is becoming increasingly clear that reversal of myelin-mediated inhibition alone will not be sufficient to produce functional recovery from spinal cord injury, and that other factors, such as astroglial scarring, the expression of chondroitin sulfate proteoglycans, neuronal cell death, and lack of neurotrophic support, must also be taken into consideration. Combinatorial approaches therefore hold a great deal of promise, and we hope to initiate a dialogue on how stem cell transplantation, chondroitinase ABC, gene therapy, growth-promoting agents, and other methods can be combined to optimize functional recovery. We introduce this topic in honor of the life and work of Dr. Marie T. Filbin (1955-2014). Through these articles, we highlight past achievements in the field, novel findings, unanswered questions and innovative ideas that we hope will lead to new advances in axonal regeneration.
MAG --- Omgp --- axonal regeneration --- myelin-associated inhibitors --- CNS regeneration --- Nogo --- cAMP --- MAG --- Omgp --- axonal regeneration --- myelin-associated inhibitors --- CNS regeneration --- Nogo --- cAMP
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The next healthcare revolution will apply regenerative medicines using human cells and tissues. The aim of the regenerative medicine approach is to create biological therapies or substitutes in vitro for the replacement or restoration of tissue function in vivo lost through failure or disease. However, whilst science has revealed the potential, and early products have shown the power of such therapies, there is an immediate and long-term need for expertise with the necessary skills to face the engineering and life science challenges before the predicted benefits in human healthcare can be realized. Specifically, there is a need for the development of bioprocess technology for the successful transfer of laboratory-based practice of stem cell and tissue culture to the clinic as therapeutics through the application of engineering principles and practices. This Special Issue of Bioengineering on Stem Cell Bioprocessing and Manufacturing addresses the central role in defining the engineering sciences of cell-based therapies, by bringing together contributions from worldwide experts on stem cell biology and engineering, bioreactor design and bioprocess development, scale-up, and manufacturing of stem cell-based therapies.
Medicine --- electrospinning --- live-cell electrospinning --- tissue engineering --- cell seeding --- high voltage --- viability --- allogeneic cell therapy --- induced pluripotent stem cell --- human embryonic stem cell --- cell aggregate --- expansion --- differentiation --- scalable manufacturing --- scale up --- single-use bioreactor --- Vertical-Wheel --- U-shaped vessel --- computational fluid dynamics --- shear stress --- turbulent energy dissipation rates --- homogeneous hydrodynamic environment --- human pluripotent stem cells --- hepatic cell lineages --- hepatocyte differentiation --- non-parenchymal liver cells --- liver organoids --- disease modeling --- drug screening --- olfactory ensheathing cells --- spinal cord injury --- neural regeneration --- cell therapies --- adipose stem cells --- neurotrophic factors --- growth factors --- peripheral nerve injuries --- fibrin nerve conduits --- hydrogels --- stem cells delivery --- axonal regeneration --- Schwann cells --- stromal vascular fraction --- stem cell --- adipose-derived stem cell --- infrapatellar fat pad --- knee --- arthroscopy --- arthrotomy --- bioreactor --- hMSCs --- microcarrier --- bioprocess --- embryonic stem cells --- mesenchymal stromal cells --- blood platelets --- cell culture techniques --- progenitor cells --- human adipose stem cells (hASCs) --- serum- and xeno-free conditions --- UrSuppe stem cell culture medium --- autologous therapy --- kinetic growth modeling --- segregated and unstructured growth model --- model predictive control --- bio-process --- cell growth --- lactate --- advanced therapy medicinal products --- electrospinning --- live-cell electrospinning --- tissue engineering --- cell seeding --- high voltage --- viability --- allogeneic cell therapy --- induced pluripotent stem cell --- human embryonic stem cell --- cell aggregate --- expansion --- differentiation --- scalable manufacturing --- scale up --- single-use bioreactor --- Vertical-Wheel --- U-shaped vessel --- computational fluid dynamics --- shear stress --- turbulent energy dissipation rates --- homogeneous hydrodynamic environment --- human pluripotent stem cells --- hepatic cell lineages --- hepatocyte differentiation --- non-parenchymal liver cells --- liver organoids --- disease modeling --- drug screening --- olfactory ensheathing cells --- spinal cord injury --- neural regeneration --- cell therapies --- adipose stem cells --- neurotrophic factors --- growth factors --- peripheral nerve injuries --- fibrin nerve conduits --- hydrogels --- stem cells delivery --- axonal regeneration --- Schwann cells --- stromal vascular fraction --- stem cell --- adipose-derived stem cell --- infrapatellar fat pad --- knee --- arthroscopy --- arthrotomy --- bioreactor --- hMSCs --- microcarrier --- bioprocess --- embryonic stem cells --- mesenchymal stromal cells --- blood platelets --- cell culture techniques --- progenitor cells --- human adipose stem cells (hASCs) --- serum- and xeno-free conditions --- UrSuppe stem cell culture medium --- autologous therapy --- kinetic growth modeling --- segregated and unstructured growth model --- model predictive control --- bio-process --- cell growth --- lactate --- advanced therapy medicinal products
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