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Stem cell-based therapies have become a promising treatment that leverages the regenerative potential of stem cells to repair damaged neural tissue and neural circuits for the treatment of various nervous system diseases.
Recently, the European Journal of Medical Research published a literature review on the current progress, challenges and future prospects of stem cell treatment of neurological diseases.
This comprehensive review provides an in-depth analysis of the current status of use of stem cells in the treatment of major neurological diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI) and other related diseases.
What is a nervous system disease
Nervous system diseases include a variety of debilitating diseases that affect the central and peripheral nervous systems, resulting in progressive damage and loss of nervous tissue. These diseases include neurodegenerative diseases that are characterized by the accumulation of abnormal protein aggregates and the gradual loss of specific groups of neurons.
Examples of these diseases are Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Other nervous system diseases such as multiple sclerosis (MS) and spinal cord injury (SCI) involve damage to the myelin and axon, which disrupts nerve transmission and leads to dysfunction. Cerebrovascular diseases, including stroke and traumatic brain injury (TBI), can lead to acute nerve tissue damage and subsequent neuroinflammation, leading to long-term disability.
Nervous system diseases place a heavy burden on global health, affecting millions of people around the world, and causing huge medical costs and social impact.
Currently, approaches to treating nervous system diseases focus mainly on controlling symptoms and slowing disease progression, rather than addressing underlying pathology. Part of the reason is that the exact causes of many neurological disorders remain unknown, limiting our ability to develop targeted disease-modified therapies. Given the limitations of current treatment methods, there is an urgent need for new methods that can effectively regenerate damaged nerve tissue, replace lost neurons, and promote functional recovery from nervous system diseases.
By leveraging the regenerative capabilities of stem cells, stem cell therapy has become a viable option for treating the underlying pathophysiology of nervous system diseases. Stem cells are popular in regenerative medicine because of their ability to self-renew and differentiate into different cell types.
Stem cells have multiple therapeutic applications in nervous system diseases, including immune regulation, cell replacement, paracrine signaling and stimulation of endogenous repair mechanisms. Preclinical studies in animal models have shown that stem cells can differentiate into neuronal and glial cell lineages, integrate into host neural circuits, and promote functional recovery in various nervous system diseases. However, the clinical transformation of stem cell therapies faces many challenges, including optimizing cell manufacturing, delivery methods and safety assessments.
This review aims to deeply analyze the current status of stem cells in the treatment of nervous system diseases, focusing on the latest progress and clinical applications. In addition, this review will discuss the mechanisms by which stem cells treat nervous system diseases, critically review preclinical and clinical evidence on their effectiveness and safety, and highlight challenges and future directions in this field.
By synthesizing the latest research results and expert opinion, this review aims to inform researchers, clinicians, and stakeholders of the potential and limitations of stem cell therapies in revolutionizing the treatment of nervous system diseases.
Mechanism of stem cells in treating nervous system diseases
Stem cells are undifferentiated cells with the unique ability to self-renew and differentiate into various cell types, making them a valuable tool in regenerative medicine. Understanding the basic characteristics and mechanisms of stem cells is crucial for their therapeutic applications in nervous system diseases. This section outlines the mechanisms of action of stem cells in treating nervous system diseases.
Stem cells play a therapeutic role in nervous system diseases through multiple mechanisms, which can be roughly divided into cell replacement, paracrine signaling, immune regulation and stimulation of endogenous repair processes.
Cell replacement: Stem cells can differentiate into specific neuron and glial cell types, potentially replacing damaged or lost nerve cells in nervous system diseases. For example, dopaminergic neurons from stem cells can be transplanted into the striatum to replace degenerative neurons in Parkinson's disease. However, the degree of cell replacement and the functional integration of transplanted cells vary in different neurological diseases and require further optimization.
Paracrine signaling: Stem cells secrete a variety of biologically active molecules, including growth factors, cytokines, and extracellular vesicles, which can exert neuroprotective, anti-inflammatory, and regenerative effects on host nervous tissue. These paracrine factors promote the survival and regeneration of endogenous nerve cells, regulate immune responses, and enhance angiogenesis and neural plasticity. It is believed that the paracrine mechanism of stem cells plays a crucial role in their therapeutic effectiveness, especially when cell replacement alone may not be enough.
Immunomodulation: Neuroinflammation is a common feature of many nervous system diseases, causing nerve damage and hindering the repair process. Stem cells, especially MSCs, have immunoregulatory properties that regulate immune responses and create a more conducive environment for nerve repair. These cells can interact with various immune cells, such as T cells, B cells, and microglia, and regulate their activity through direct cell-to-cell contact and secretion of soluble factors. By reducing nerve inflammation and promoting pro-regenerative immune responses, stem cells can indirectly support nerve repair and functional recovery.
Stimulate endogenous repair: In order to promote the proliferation, differentiation and integration of endogenous stem and progenitor cells into damaged neural tissue, stem cells can activate and mobilize these cells in the brain. To achieve this goal, growth factors and chemokines can be secreted to attract endogenous stem cells to the site of injury and promote their survival and differentiation. In addition, stem cells can expand the neurogenic and angiogenic microenvironment of the brain and improve conditions for endogenous repair mechanisms.
The treatment mechanism of stem cells in nervous system diseases is complex and multifaceted, usually involving multiple mechanisms such as cell replacement, paracrine signaling, immune regulation, and stimulation of endogenous repair. The relative contribution of each mechanism may vary depending on the specific neurological disease, the type of stem cells used, and the route and timing of administration.
Understanding these mechanisms is critical to optimizing stem cell-based therapies and developing targeted therapies for neurological diseases.
Stem cells treat specific nervous system diseases
01
Stem cell treatment of Alzheimer's disease
Alzheimer's disease: Amyloid beta protein (Aβ) plaques and neurofibrillary tangles accumulate in Alzheimer's disease (AD), a progressive neurodegenerative disease that impairs memory, causes neuron death and reduces cognitive function.
Current medical treatments, such as cholinesterase inhibitors and memantine, can relieve symptoms but cannot resolve underlying pathology or stop the progression of the disease. Stem cell-based therapies have been proposed as potential strategies to address multiple aspects of Alzheimer's disease pathology, including replacing lost neurons, providing neuroprotection and regulating neuroinflammation.
Clinical trial of stem cell therapy for Alzheimer's disease
To date, only a limited number of small-scale clinical trials have studied the safety and feasibility of stem cell therapy in AD patients. A phase I trial using human cord blood MSCs (hUCB-MSCs) demonstrated the safety and tolerability of repeated intravenous infusions in AD patients, and there is evidence of stabilization of cognitive function.
Another phase 1 trial using autologous adipose-derived MSCs (ADSCs) showed that stem cell therapy is safe and has potential efficacy in slowing cognitive decline in patients with mild to moderate AD.
Challenges and future directions for stem cell treatment of Alzheimer's disease
Obstacles and future prospects: Although preclinical results show promise, various obstacles must be overcome to successfully apply stem cell therapy to the clinical treatment of AD. These include improving the efficiency and quality of stem cells, improving the vitality and effective integration of transplanted cells, and designing precise delivery techniques to specific brain areas affected by AD. In addition, well-designed clinical trials need to determine the optimal timing of intervention, long-term safety and effectiveness, and the potential need for repeated treatment.
Future directions for stem cell treatment of Alzheimer's disease: May include the use of genetically modified stem cells to enhance their therapeutic properties, such as increasing the secretion of neurotrophic factors or Aβ degrading enzymes. Combining stem cell therapy with other therapeutic approaches, such as Aβ immunization or small molecule inhibitors of Aβ and tau pathology, can produce synergistic benefits. A 3D organoid model derived from patient-specific iPSC may also help in drug screening and personalized treatment strategies.
02
Stem cell treatment of Parkinson's disease
Parkinson's disease: Parkinson's disease (PD) is a neurodegenerative disease that gradually causes the death of dopaminergic neurons in the substantia nigra dense (SNpc). This can cause motor symptoms, including tremors, rigidity and slowness. Current treatments, including dopaminergic drugs and deep brain stimulation, can relieve symptoms but cannot address potential neuron loss or stop disease progression. Stem cell-based therapies aim to replace lost dopaminergic neurons and restore motor function in PD patients.
It's worth noting that Parkinson's disease is more than just the loss of dopaminergic neurons. Its pathophysiology is complex, involving multiple neurotransmitter systems, protein aggregation, neuroinflammation, and various neural circuit dysfunction. If stem cell therapy wants to truly change or cure the disease, it needs to address multiple aspects of PD pathology. Recent research has highlighted additional challenges, including the possible spread of alpha-synuclein pathology to transplanted cells and the need to restore broader neural circuit function in addition to dopamine replacement.
Clinical trial of stem cell therapy for Parkinson's disease
Multiple clinical trials have investigated the safety and effectiveness of stem cell therapy in PD patients. Early trials using fetal ventral midbrain (FVM) tissue grafts have shown mixed results, with some patients showing long-term clinical benefits and others experiencing graft-induced dyskinesia.
Recently, clinical trials using human ESC-derived dopaminergic progenitor cells have shown good prospects. A phase 1/2 trial reported the safety and survival of transplanted cells in PD patients, with some evidence of improvement in exercise.
An ongoing phase 1 trial (NCT03119636) has investigated the safety and effectiveness of human ESC-derived dopaminergic progenitor cells in PD patients. Clinical trials using autologous iPSC-derived dopaminergic neurons are also in the planning stage.
Challenges and future directions for clinical trials of stem cell therapy for Parkinson's disease
Although significant progress has been made in stem cell therapy for PD, some challenges remain. These include optimizing the differentiation and purification of dopaminergic neurons, ensuring graft survival and functional integration, and minimizing the risk of graft-induced dyskinesia. Strategies to improve graft survival are being explored, such as co-grafting with supportive cell types or neuroprotective agents. Developing standardized cell manufacturing and quality control protocols is also critical to the repeatability and scalability of stem cell therapies.
Future directions for stem cell treatment of Parkinson's disease: Could involve gene editing techniques to correct disease-causing mutations in patient-specific iPSC. Cell encapsulation or bioengineered scaffolds can improve graft survival and integration rates. Combination approaches (such as co-administration of neurotrophic factors or use of neuroprotective agents) can enhance the therapeutic effectiveness of stem cell therapy.
Stem cell therapy is expected to be a disease-modified treatment for PD, aiming to replace lost dopaminergic neurons and restore motor function. Although encouraging findings have been made in preclinical studies and early clinical trials, further research is needed to overcome obstacles and enhance treatment options.
03
Stem cell treatment of multiple sclerosis
Multiple sclerosis: Multiple sclerosis (MS) is a long-term inflammatory disease of the central nervous system in which the immune system attacks and destroys the protective sheath of nerve fibers. This damage can cause nervous system problems and dysfunction.
Currently, treatment methods for MS mainly focus on immune regulation and symptom management, but cannot effectively promote myelination or prevent progressive neurodegeneration. Stem cell-based therapies aim to promote re-myelin, provide neuroprotection and regulate the immune response in MS.
Among neurological diseases, multiple sclerosis (MS) stands out because of the most advanced clinical application of stem cell therapy. Autologous hematopoietic stem cell transplantation (aHSCT) is currently routinely used in medical centers around the world to treat invasive MS. This approach aims to "reset" the immune system and stop disease progression.
Clinical trial of stem cell therapy for multiple sclerosis
Multiple clinical trials have investigated the safety and effectiveness of stem cell therapy in patients with MS. aHSCT has been explored as a potential treatment for aggressive MS that could reset the immune system and stop disease progression. Comparing aHSCT with disease modification therapies, aHSCT was found to be superior in preventing disease progression and achieving sustained improvement in neurological function. Long-term follow-up studies have shown that a significant proportion of patients have no disease activity for 5 years or more after treatment.
Although some studies have shown promising results with long-term stabilization or improvement of disability in some patients, the procedure carries significant risks. It is currently only used for specific patients with highly active disease. Clinical trials using MSCs are also being carried out in MS patients, focusing on safety and feasibility. Intravenous administration of autologous MSCs is well tolerated, and there is evidence of their potential efficacy in reducing inflammatory activity and promoting neuroprotection.
Challenges and future directions
Although stem cell therapy is expected to become an effective treatment for MS, some challenges still need to be addressed.
One of the main challenges is ensuring the survival, differentiation and functional integration of the transplanted cells in the host central nervous system. Strategies to improve graft survival and promote directed migration to demyelinated sites are being explored.
Another challenge is the possibility of transplant rejection or secondary autoimmunity. The use of autologous or genetically modified stem cells and the development of improved immunosuppression protocols may help mitigate these risks.
Future directions for stem cell therapy for multiple sclerosis: Could include the use of gene editing technology to create "off-the-shelf" cell products with enhanced myelin regeneration or immunoregulatory properties. Developing biomaterials and tissue engineering methods to create scaffolds that support cell survival and guide axon regeneration is also an active area of research. Combination therapies that target multiple aspects of MS pathology, such as neuroinflammation, oxidative stress, and mitochondrial dysfunction, may enhance the therapeutic potential of stem cell transplantation.
04
Stem cell treatment for stroke
Stroke: Stroke is the leading cause of death and disability worldwide, characterized by a sudden loss of blood supply to the brain, leading to neuronal damage and dysfunction.
Current treatment of stroke mainly focuses on restoring blood flow and providing supportive care, but cannot effectively address long-term neurological deficits. Stem cell-based therapies promote neuron repair, regulate inflammation and enhance functional recovery after a stroke.
Clinical trial of stem cell therapy for stroke
Multiple clinical trials have investigated the safety and feasibility of stem cell therapy in stroke patients. A meta-analysis of early clinical trials using MSCs to treat patients with ischemic stroke reported good safety and potential improvements in functional outcomes. However, the efficacy of MSC transplantation on stroke remains to be determined in a larger randomized controlled trial.
Recently, the TREASURE trial, a Phase II/III study of intravenous injection of cord blood-derived MSCs into patients with acute ischemic stroke, also failed to show significant improvement in functional outcomes at 90 days. These results highlight the need to further optimize stroke stem cell therapy, including selecting the patients most likely to benefit, the timing and route of administration, and the potential of combination therapies.
Challenges and future directions
Although stem cell therapy is expected to become the best treatment for stroke, many challenges still need to be addressed.
One of the major challenges is the limited survival and implantation of transplanted cells in ischemic brain tissue. Strategies to improve cell survival are being explored, such as pre-treating or genetically modifying stem cells.
Another challenge is the potential for off-target effects or adverse events, such as tumor development or stroke-related infections. The use of highly purified, well-characterized cell populations and strict safety monitoring are critical to the clinical transformation of stroke stem cell therapy.
Future directions for stem cell treatment of stroke: May include the use of biomaterials and tissue engineering methods to create a supportive microenvironment for transplanted cells and improve their survival and differentiation. Developing cell-free methods, such as using extracellular vesicles or exosomes from stem cells, may also provide a more scalable and safe alternative to cell transplantation. Combined use of neuroprotective agents or rehabilitation therapy can enhance the therapeutic effect of stem cell transplantation.
05
Stem cell treatment of spinal cord injury
Spinal cord injury: Spinal cord injury (SCI) is a serious disease that results in loss of motor and sensory function below the injury site, which often results in permanent paralysis and injury. The main goals of current SCI treatment are to stabilize the spine, prevent further injury and promote recovery. Goals for stem cell-based spinal cord injury (SCI) treatment include replacement of glial cells and missing neurons, axon regeneration, and regulation of inflammatory responses.
Clinical trial of stem cells for spinal cord injury
Multiple clinical trials have studied the safety and feasibility of stem cell therapy in SCI patients.
A systematic review and meta-analysis of clinical trials using MSC to treat SCI patients found that there were no serious adverse events in cell transplantation and there was some evidence of functional improvement. However, the small size, heterogeneity and lack of appropriate controls included studies highlight the need for broader, more well-designed trials to determine the efficacy of MSC in the treatment of SCI.
A phase II trial (NCT02302157) of intramedullary transplantation of human ESC-derived oligodendrocyte progenitor cells in patients with subacute SCI was recently completed, and the results are yet to be published. Other ongoing or planned trials have investigated the safety and efficacy of various stem cell types in SCI patients, including NSC, NPC and autologous bone marrow-derived MSC.
Challenges and future directions
Although stem cell-based SCI therapies have bright prospects, several challenges must be addressed to successfully achieve clinical transformation.
One of the main challenges is the complexity and dynamics of the damage microenvironment, which may limit the survival, differentiation and integration of transplanted cells. Strategies to increase cell survival and promote targeted differentiation are being explored, such as co-delivery of neuroprotective factors or biomaterials and tissue engineering methods.
Another challenge is the potential for adverse events after stem cell transplantation, such as neuropathic pain, abnormal autonomic reflexes, or tumor formation. Careful patient selection, strict safety monitoring and long-term follow-up are crucial to reducing these risks.
Future directions for stem cell treatment of spinal cord injuries: May include the use of gene editing technology to modify stem cells to have enhanced regenerative properties, such as increasing the secretion of neurotrophic factors or improving myelination. Combination therapies, such as combined rehabilitation therapy or the use of electrical stimulation, can enhance the therapeutic potential of stem cell transplants. In addition, identifying reliable biomarkers and imaging techniques to monitor the survival, differentiation and integration of transplanted cells in vivo is critical to optimizing and personalizing SCI stem cell therapies.
06
Stem cell treatment of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis: Muscle weakness, paralysis, and ultimately death, is the result of selective loss of motor neurons in the brain and spinal cord and is a feature of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease.
There are currently only a few treatments for ALS, mainly focusing on supportive treatment and symptom control. The goal of stem cell-based ALS treatment is to reduce neuroinflammation, restore damaged motor neurons and provide neuroprotection.
Clinical trial of stem cells in the treatment of amyotrophic lateral sclerosis
Multiple early clinical trials have studied the safety and feasibility of stem cell therapy in ALS patients. Intraspinal transplantation of fetal spinal-derived NSC in ALS patients is safe and well-tolerated, and there is evidence that it may be effective in slowing disease progression.
However, a subsequent Phase 2 trial showed that NSC did not significantly improve functional outcomes or survival compared with placebo. Intrathecal injection of autologous MSC in ALS patients has also been explored, focusing on safety and tolerability. Although these early trials provide proof of concept for the feasibility of stem cell transplantation in ALS, more extensive randomized controlled trials are needed to determine the effectiveness of these methods.
Challenges and future directions
Despite encouraging preclinical results, the clinical transformation of stem cell therapy in ALS still faces several challenges.
One of the main challenges is the complex and multi-factorial pathogenesis of ALS, which may limit the therapeutic effectiveness of simple cell replacement. Strategies to improve the survival, integration and function of transplanted cells in the harsh microenvironment of ALS are currently being explored, such as simultaneous transplantation of supporting glial cells or the use of neuroprotective factors.
Another challenge is the potential for immune rejection or adverse events, such as transplant-induced dyskinesia or tumor development. The use of autologous or genetically modified stem cells and improved immunosuppression protocols may help mitigate these risks.
Future directions for stem cell treatment of ALS: Could involve gene editing techniques to correct mutations in patient-specific iPSC that cause ALS, which can then be differentiated into healthy motor neurons for transplantation. The use of biomaterials and tissue engineering methods to create scaffolds that support cell survival and guide axon regeneration is also an active area of research.
Combination approaches: For example, co-administration of neuroprotective agents or use of anti-inflammatory drugs can enhance the therapeutic potential of stem cell transplantation. Developing new drug delivery methods, such as intramuscular or intravascular administration of stem cells, could provide a less invasive and more scalable approach to the cellular treatment of ALS.
07
Stem cells treat brain damage
Traumatic brain injury: Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. It is caused by sudden physical damage to the brain caused by external forces such as falls, car accidents, or violence. Primary injury triggers a range of secondary injury mechanisms, including neuroinflammation, oxidative stress, excitotoxicity and apoptosis, leading to progressive neuron loss and dysfunction.
Current treatment of TBI mainly focuses on reducing secondary injury, controlling intracranial pressure and promoting functional recovery through rehabilitation treatment. However, there is currently no effective therapy that can reverse the damage and restore function in patients with chronic TBI. Stem cell-based therapies aim to replace lost neurons and glial cells, regulate the inflammatory response, and promote neurogenesis and angiogenesis in TBI.
Clinical trial of stem cells in treating traumatic brain injury
Multiple early clinical trials have studied the safety and feasibility of stem cell therapy in patients with TBI. A phase 1/2a study that administered intravenous injection of autologous bone marrow-derived monocytes (BMMNC) in patients with acute severe TBI showed that this method was safe and had a trend to improve neurological outcomes.
Another Phase 1 study performed intracerebral transplantation of human NSC in patients with chronic TBI, and showed that the method was safe and feasible, and there was evidence that the method improved nervous system function.
However, more extensive randomized controlled trials are needed to determine the effectiveness of these methods in improving functional outcomes and quality of life in patients with TBI.
Challenges and future directions
Although stem cell-based TBI therapies have promising prospects, several challenges must be addressed to successfully achieve clinical transformation.
One of the main challenges is the heterogeneity of TBI, which may vary in terms of the mechanism, location and severity of injury, as well as patient age and comorbidities. Developing personalized stem cell therapies tailored to the specific needs of each patient may help maximize treatment outcomes.
Another challenge is the potential for adverse events after stem cell transplantation, such as seizures, infections or tumors. Careful patient selection, strict safety monitoring and long-term follow-up are crucial to mitigating these risks.
Future development directions for stem cell treatment of traumatic brain injury: may include the use of gene editing technology to enhance the regenerative characteristics of transplanted cells, such as overexpressing neurotrophic factors or anti-inflammatory cytokines. The combined use of combined technologies such as neuroprotective drugs, neurorepair treatments or rehabilitation may increase the therapeutic potential of stem cell transplants.
In addition, the development of non-invasive imaging methods such as PET and MRI to track the migration, survival and differentiation of transplanted cells in the body is critical to customizing and simplifying stem cell treatment for traumatic brain injury.
08
Stem cell treatment of Huntington's disease
Huntington's disease: Huntington's disease (HD) is a hereditary neurodegenerative disease caused by repeated amplification of the trinucleotide of the Huntington gene, resulting in the production of mutated Huntington protein, which in turn causes progressive neuronal loss and dysfunction, especially in the striatum and cortex.
Current treatments for Huntington's disease are limited and focus on controlling symptoms, such as chorea and mental disorders. Stem cell-based therapies aim to replace lost neurons, provide neuroprotection, and regulate neuroinflammation in Huntington's disease.
Clinical trial of stem cell therapy for Huntington's disease
To date, few clinical trials have investigated the safety and feasibility of stem cell therapy in Huntington's disease patients. A phase 1 trial of fetal striatum tissue transplantation in Huntington's disease patients demonstrated the safety and feasibility of the method, and there is some evidence of graft survival and clinical benefit. However, a follow-up study found that the transplanted cells developed pathology similar to Huntington's disease over time, suggesting that cell replacement alone may not stop the disease from progressing.
Recently, a phase 1/2 trial has been launched for transplanting human ESC-derived neural progenitor cells into the striatum of Huntington's disease patients (NCT03252080). The trial is designed to assess the safety, tolerability and preliminary efficacy of the method, and results are expected to be announced in the next few years.
Challenges and future directions
Although stem cell-based therapies for Huntington's disease have promising prospects, several challenges must be addressed to successfully achieve clinical transformation.
One of the major challenges is that due to the presence of mutated Huntington protein in the host environment, transplanted cells may acquire pathology associated with Huntington's disease over time. Strategies to reduce this risk are being explored, such as genetically corrected autologous iPSC or co-transplantation of neuroprotective factors.
Another challenge is the need to target cells to affected brain areas, because Huntington's disease can experience widespread neuron loss and circuit dysfunction.
Developing new drug delivery methods, such as intraventricular or intrathecal injection of stem cells, could provide a less invasive and broader approach to cellular treatment of Huntington's disease.
09
Stem cell treatment of epilepsy
Epilepsy: Repeated unprovoked seizures are typical features of epilepsy, a chronic nervous system disease caused by abnormally high levels of brain neuron activity. Although antiepileptic drugs (AEDs) are the cornerstone of epilepsy treatment, more than one-third of patients still do not respond to the drug. To restore the proper balance between excitement and inhibition in the brain of people with epilepsy, stem cell therapy has become a viable adjunct or alternative treatment option for treating drug-resistant epilepsy.
Clinical trial of stem cell therapy for epilepsy
To date, few clinical trials have studied the safety and effectiveness of stem cell therapy in patients with epilepsy.
A phase 1 clinical trial that administered intravenous injection of autologous bone marrow-derived monocytes (BMMNC) in children with refractory epilepsy demonstrated its safety and feasibility, and showed evidence of a reduced seizure frequency.
Another pilot study of autologous BMMNC intracerebral transplantation in adult patients with drug-resistant medial temporal lobe epilepsy also showed that the therapy is safe and may be effective in reducing the frequency of seizures.
Challenges and future directions
Although stem cell-based epilepsy therapies have promising prospects, several challenges must be addressed to successfully achieve clinical transformation.
One of the main challenges is the complex and multifactorial nature of epilepsy, which may require personalized stem cell therapies tailored to each patient's specific epileptogenic mechanisms.
Another challenge is that adverse events can occur after stem cell transplantation, such as transplant rejection, tumor formation or worsening seizures. Careful patient selection, strict safety monitoring and long-term follow-up are crucial to mitigating these risks.
Future directions for stem cell therapy for epilepsy: Gene editing techniques may be involved to create stem cell-derived GABAergic interneurons with enhanced anticonvulsant properties or reduced immunogenicity. Developing advanced delivery methods (such as stereotactic surgery or convection-enhanced delivery) to achieve targeted and controllable transplantation of stem cells to epileptic lesions is also an active area of research.
In addition, identifying reliable biomarkers and advanced neuroimaging technologies to guide patient selection, monitor the fate of transplanted cells, and assess the in vivo efficacy of stem cell therapy is critical to optimizing and individualizing stem cell-based epilepsy treatment.
other emerging applications
In addition to the neurological disorders discussed above, stem cell-based therapies have shown potential to treat a variety of other neurological disorders, such as cerebral palsy, autism spectrum disorder (ASD) and peripheral nerve damage.
Stem cell-based therapies, particularly MSCs and adipose stem cells (ADSC), have shown promise in preclinical studies to promote nerve regeneration, myelin regeneration and functional recovery. These cells can be transplanted directly into the injured nerve, or they can be transported through nerve conduits or other biomaterial scaffolds. Some early clinical trials have studied the safety and feasibility of stem cell therapy for peripheral nerve injury, and there is evidence of improvements in sensory and motor function.
Challenges and future directions
Although stem cell therapy is expected to be used in these neurological diseases, multiple challenges must be addressed to successfully achieve clinical transformation. These challenges include the heterogeneity of the patient population, the complexity and multifactorial nature of the underlying pathology, and the potential for adverse events after stem cell transplantation.
Future directions may include developing personalized stem cell therapies tailored to the specific needs of each patient, using gene editing technology to enhance the therapeutic properties of stem cells, and exploring combined methods to improve the efficacy of stem cell transplants.
In addition to the well-researched diseases discussed above, stem cell therapies have also shown potential to treat neurological diseases. With the development of regenerative medicine, it is hoped that stem cell therapy will become a viable option for treating various neurological diseases, thereby improving the quality of life of patients and their families.
Discussion and Future Outlook
In recent years, significant progress has been made in stem cell-based therapies for nervous system diseases, with encouraging results achieved in preclinical research and early clinical trials. As this comprehensive review highlights, various stem cell types, including NSC, MSC and iPSC, have shown potential to treat multiple neurological disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, stroke, spinal cord injury and traumatic brain injury.
Looking to the future, exciting developments and breakthroughs are expected to be achieved in the field of stem cell-based treatment of nervous system diseases. The fusion of stem cell biology with other cutting-edge technologies, such as gene editing, single cell genomics, organoid models, and advanced neuroimaging, holds great promise for the development of personalized and targeted treatments for neurological diseases. A growing understanding of the complex interactions between the nervous system, immune system and microbiome may also open up new avenues for stem cell-based therapies that leverage the body's inherent regenerative capabilities.
In short, although stem cell treatment of nervous system diseases is still in the early stages of development, the progress made so far is encouraging and the future has broad prospects. Through continued research, collaboration and innovation, it is hoped that stem cell therapy will become a safe, effective and accessible treatment option for millions of patients with neurological diseases around the world, improving their quality of life and reducing the burden on the healthcare system.