In vivo Direct Conversion of Astrocytes to Neurons Maybe a Potential Alternative Strategy for Neurodegenerative Diseases

Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.

An implantable human stem cell-derived tissue-engineered rostral migratory stream for directed neuronal replacement

The rostral migratory stream (RMS) facilitates neuroblast migration from the subventricular zone to the olfactory bulb throughout adulthood. Brain lesions attract neuroblast migration out of the RMS, but resultant regeneration is insufficient. Increasing neuroblast migration into lesions has improved recovery in rodent studies. We previously developed techniques for fabricating an astrocyte-based Tissue-Engineered RMS (TE-RMS) intended to redirect endogenous neuroblasts into distal brain lesions for sustained neuronal replacement. Here, we demonstrate that astrocyte-like-cells can be derived from adult human gingiva mesenchymal stem cells and used for TE-RMS fabrication. We report that key proteins enriched in the RMS are enriched in TE-RMSs. Furthermore, the human TE-RMS facilitates directed migration of immature neurons in vitro. Finally, human TE-RMSs implanted in athymic rat brains redirect migration of neuroblasts out of the endogenous RMS. By emulating the brain’s most efficient means for directing neuroblast migration, the TE-RMS offers a promising new approach to neuroregenerative medicine.

A fully biodegradable and self-electrified device for neuroregenerative medicine

Peripheral nerve regeneration remains one of the greatest challenges in regenerative medicine. Deprivation of sensory and/or motor functions often occurs with severe injuries even treated by the most advanced microsurgical intervention. Although electrical stimulation represents an essential nonpharmacological therapy that proved to be beneficial for nerve regeneration, the postoperative delivery at surgical sites remains daunting. Here, a fully biodegradable, self-electrified, and miniaturized device composed of dissolvable galvanic cells on a biodegradable scaffold is achieved, which can offer both structural guidance and electrical cues for peripheral nerve regeneration. The electroactive device can provide sustained electrical stimuli beyond intraoperative window, which can promote calcium activity, repopulation of Schwann cells, and neurotrophic factors. Successful motor functional recovery is accomplished with the electroactive device in behaving rodent models. The presented materials options and device schemes provide important insights into self-powered electronic medicine that can be critical for various types of tissue regeneration and functional restoration.

Adipose Stem Cell-Based Clinical Strategy for Neural Regeneration: A Review of Current Opinion

Nerve injury is a critical problem in the clinic. Nerve injury causes serious clinic issues including pain and dysfunctions for patients. The disconnection between damaged neural fibers and muscles will result in muscle atrophy in a few weeks if no treatment is applied. Moreover, scientists have discovered that nerve injury can affect the osteogenic differentiation of skeletal stem cells (SSCs) and the fracture repairing. In plastic surgery, muscle atrophy and bone fracture after nerve injury have plagued clinicians for many years. How to promote neural regeneration is the core issue of research in the recent years. Without obvious effects of traditional neurosurgical treatments, research on stem cells in the past 10 years has provided a new therapeutic strategy for us to address this problem. Adipose stem cells (ASCs) are a kind of mesenchymal stem cells that have differentiation potential in adipose tissue. In the recent years, ASCs have become the focus of regenerative medicine. They play a pivotal role in tissue regeneration engineering. As a type of stem cell, ASCs are becoming popular for neuroregenerative medicine due to their advantages and characteristics. In the various diseases of the nervous system, ASCs are gradually applied to treat the related diseases. This review article focuses on the mechanism and clinical application of ASCs in nerve regeneration as well as the related research on ASCs over the past decades.

From Zero to Neuro-Reprogramming: Innovations in Translational Neuroregenerative Medicine

Acquiring live human nervous tissue for research presents ethical and technical constraints. As a result, clinicians and scientists resort to using animal models to investigate human neuronal development and degeneration. However, innate species differences in neurobiology have hindered the translation of disease pathologies and development of therapeutic strategies. The discovery of endogenous neural stem cells (NSCs) and their examination has been critical for neuronal development, degeneration and regeneration. NSCs can exist in different developmental stages, embryonic through adult, and possess the capacity to generate the various cells that make up the nervous system. Importantly, human somatic cells can be obtained non-invasively and genetically reprogrammed into NSCs providing an ethically viable source of stem cells for translational study and potential therapy. Novel methods to generate NSCs of various developmental origins and regional identities are rapidly evolving to provide safer, quicker, and more efficient reprogramming strategies. Reprogrammed NSCs share many molecular and functional attributes with their endogenous NSC counterparts and can be used for in vitro modelling at a large scale. The accessibility to study patient specific NSCs allows the causal inferences of human disease mechanisms that may be unfeasible to model in animals. Despite the novelty of this burgeoning field, the opportunity for translational discoveries in neuronal development and degeneration and for therapeutic applications is unprecedented. This review will highlight the advances in manufacturing NSCs and their translational implications for disease modelling and potential treatment of the nervous system.

Neuroregenerative Medicine in TBI

Traumatic brain injury (TBI) is affecting a large population with permanent physical disabilities and neurobehavioral abnormalities worldwide. Cell death in multiple brain regions is one of the most common pathological changes seen after TBI. Neuronal replacement then represents an urgent need for functional recovery. Neural stem cells (NSC) to mediate endogenous neurogenesis in the adult brain holds great promise for neural repair by replacing dead neurons and rebuilding damaged connections. It has been shown that TBI promotes NSC proliferation, detected in both the forebrain and the hippocampus, displaying an intrinsic neuroplasticity in response to injury. Thus, endogenous neurogenesis is an appropriate target for clinical interference aimed at neural repair post-trauma.