Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)re...Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)repair.It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics challenging.Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels.Extracellular vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation.At the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative processes.This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels.The rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain.This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur.Finally,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of multi-modal neuroimaging analysis to establish non-invasive,in vivo,quantifiable imagingbased biomarkers for CNS repair are discussed,aiming for more effective and safe clinical translation of such regenerative therapies to humans.展开更多
The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of ef...The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.展开更多
基金This work was supported by the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)the National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM).
文摘Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)repair.It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics challenging.Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels.Extracellular vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation.At the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative processes.This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels.The rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain.This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur.Finally,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of multi-modal neuroimaging analysis to establish non-invasive,in vivo,quantifiable imagingbased biomarkers for CNS repair are discussed,aiming for more effective and safe clinical translation of such regenerative therapies to humans.
基金supported by Onassis Foundation(to MT)the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM)
文摘The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.
