The progress and challenge of stem cell therapy in some central neuropathic diseases.

1. Stem cell classification Stem cells can be divided into embryonic stem cells (ESC) and adult stem cells (ASCs) according to cell source and cell development stage.
can be divided into omnipotent stem cells (TSC), omnipotent stem cells (HSC) and specialized stem cells (USC) according to differentiation potential.
In 2006, Shinya Yamanka discovered induced omnicnicnicnic stem cells (iPSCs), which rule out ethical arguments that can be generated from patients' own cells, but still have many challenges to address before iPSCs-derived cells can be applied to cell therapy.
these challenges include detecting and removing cells that are not fully induced differentiation, addressing genomic and supergenetic changes in the resulting cells, and overcoming possible tumor-inducing effects during transplantation.
Figure 1 Stem cell sources and isolated and proliferating cells (Photo: 10.1111/cns.13247) 2 Clinical advances Stem cell foundation and clinical trials have developed rapidly in recent years, and to date, the WHO International Clinical Trial Registry has registered more than 3,000 clinical trials involving the use of adult stem cells, Phase III clinical trials and more than 262.
involves many different areas such as neuropathy, cardiovascular disease, diabetes, blood disease and cancer.
so far, CDE has accepted 14 applications for clinical trials for stem cell therapy, 10 of which have been implied.
16 stem cell therapy products are available worldwide.
Table 1 Global Listed Stem Cell Products Data Sources: Pharmaceutical Advisory Analysis 3, Progress of Stem Cell Therapy in Central Nervous Diseases Neurological Disorders Includes a Range of Different Central and Peripheral Nervous System Disorders, which have limited treatment options and are still low in drug approval rates for improved treatment compared to other therapeutic areas.
stem cell therapy offers hope for the treatment of neurological disorders, and to date, more than 200 clinical studies using a variety of stem cell methods to treat neurological diseases have been registered, mainly multiple sclerosis, stroke, Parkinson's and spinal cord injuries.
Stem cells have a variety of therapeutic potentials in the treatment of central neuropathy and can be repaired by nerve damage in several ways (Figure 2): a. Transplanted stem cells can be migrated to damaged nerve sites, and damaged nerve cells can be repaired by cell replacement to replace dead or damaged nerve cells in the body; Secretion of a large number of nerve cell activity growth factors and nutritional factors, activation of nerve cells, promote the regeneration and reconstruction of new cells, secretion of angiogenesic factors, promote angiogenesic site, c. immunomodulation, stem cells can regulate the number of immune cells to reach the pathological site and secrete different levels of cytokines affect each other, play an anti-inflammatory protective role; Figure 2 Stem cells and the treatment of neurological disorders (Photo: doi:10.7196/SAMJ.2019.v109i8b.14009) 3.1 Stem cells for the treatment of Parkinson's disease Currently, stem cells used in the clinical treatment of Parkinson's disease are mainly neural stem cells, Embryonic stem cells, interstumed stem cells and induced erythmatic stem cells are now considered by most scholars to be the most promising stem cell option for PD.
in August 2018, a team at Kyoto University in Japan approved the first clinical trial using iPSC to treat PD, which recruited seven patients with moderate PD to use iPSC, an allogeneic body, to produce dopamine-energy ancestral cells. Transplanting the procedure into a patient's brain with a special device and giving immunosuppressant drugs to avoid immune rejection have so far shown that the treatment is safe, and the researchers say that if the trial goes ahead, the drug could be sold to patients as early as 2023 under Japan's rapid approval system for regenerative drugs.
clinical trials in China that have so far failed to investigate and use iPSC, most of the trials that have taken place have used umbilical cord-filled stem cells and autobiographical bone marrow stem cells.
searched for "stem celltherapy" and "Parkinson's Disease" on the clinical trials and collected 23 clinical trials, most of which were in clinical phase I/II and one in clinical phase II/III, in which neural stem cell trials were conducted at Suzhou University's Second Affiliated Hospital using nasal administration, with no clinical results yet to be found.
3.2 Muscular atrophy lateral sclerosis (ALS) amyotrophic lateral sclerosis (ALS) is an aggressive neurological disorder that attacks nerve cells in the cerebral cortivity, brain trunk, and spinal cord.
first attempt to treat ALS was by transplanting MSC in mouse models, which proved that stem cell therapy for ALS was promising, and that injecting stem cells into the spinal cord of mice could delay the occurrence of ALS and improve survival.
-R was approved by the Korean Ministry of Food and Drug Safety in July 2014 and launched in February 2015, but has not yet conducted Phase III clinical trials.
current clinical trials are almost all safety-based studies, and there are no clinical final results to prove effectiveness.
It's worth noting that while preclinical studies have shown that cells from unsympathetic individuals are better than those from ALS patients, most clinical trials have used introphy transplantation, which may explain the lack of good effectiveness data for ALS.
search for "stem celltherapy" and "ALS" on the clinical trials to find 25 ongoing clinical trials, the fastest of which is NurOwn® (MSC-NTF), in Clinical Phase III.
3.3 Stroke Is currently one of the most examined central nervous system diseases in cell therapy.
search for "stroke," "brain" and "projectation" on ClinicalTrials.gov, 45 clinical trials can be identified.
used MSC or related cells in nearly 70 percent of the trials.
a variety of cells in stroke patients, including central neurons, astrological glial cells, less protrusive glial cells and other cells, suddenly die after a stroke, and subsequent secondary damage can lead to more cell degeneration.
The difference between stroke recovery and PD is that multiple types of cells need to be regenerated, cell-to-cell interactions are seen as key to regeneration, high-quality and continuous cell regeneration is difficult under current conditions, and the goal of preventing neuron-glial cell-vascular unit death is critical to the design of stem cell therapy for regenerative medicine.
MSC has shown hope of regenerating neuron-glial cell-vascular units.
MsC's advantages in treating stroke are a. rapid separation from bone marrow, b. efficient amplification in cultures, c. easy maintenance in cultures, d. suitable for self-transplantation even during the acute stage of stroke, and e. neurotrophic effects.
treatment of MSC may be a combination of a variety of regenerative mechanisms, including angiogenesis, anti-inflammatory, anti-apoptosis, nerve cell regeneration, and cell migration and differentiation.
MSC has become the focus of many stroke clinical studies, and past trials in blood disease safety and numerous preclinical stroke studies have demonstrated its safety and effectiveness.
MSC cell delivery pathways include the brain, artery or veins, intra-brain pathways may be the most effective, but also the most invasive, and intravenous pathways may be minimally invasive but reach the target area of cells in the least, the intraoral arterial pathways are located between the two, according to the difference in the degree of stroke of patients to be selected and optimized.
2005, the world conducted the first phase I study of intravenously intravenously self-contained MSC in patients with ishemic stroke.
2014, the first Phase II clinical trial of intravenous intravenous dosing of isothermic stroke patients was published, in which the therapeutic effects of intravenous iso-MSC treatment were reported in isothermic stroke patients.
in a study using an allogeneic MSC drug in the arteries, 40 percent of stroke patients treated with stem cells showed good clinical results within 3-7 days of onset.
Japan is also conducting clinical trials of stem cells to treat strokes, such as Shichinohe's report on in-brain administration of self-contained MSCs for the subacute phase of stroke.
. Difficulties in stem cell therapy for neurological diseases 4.1 How to enhance the efficacy of stem cell therapy Stem cell therapy is considered to be the most promising treatment for neurological diseases, but the therapeutic potential of stem cells, including enhanced stem cell differentiation, migration or formation of neural networks, are key indicators of central nervous system regeneration.
electrical stimulation has become a more important way, and tests have shown that electrical stimulation can trigger transplantation of interstate substring cells in the brains of stroke rats by signaling through the chimogenic factor SDF-1 alpha, enhancing nerve cell regeneration in the hema body, in addition, electrical stimulation can improve the formation of synapses, thereby promoting the therapeutic effect of stem cell therapy, and suggesting the potential of combination therapy.
4.2 The safety of cell therapy The safety of cells of patient origin can be subject to ethical review, on the other hand, genetic modification of adult cells, stem cell amplification may lead to uncontrolled cell reproduction, the controllability of potential risks becomes an important challenge.
not editing cells from the patient's source, which can limit their viability and therapeutic potential.
can be avoided by using healthy confessions for allogeneic transplants, but these cells are at risk of immune rejection.
stem cell therapy needs to eliminate uncertain cell differentiation and reproduction factors, remove cells at risk of tumors, and purify differentiated cells.
4.3 iPSC as an introphy stem cell iPS cell has become an attractive source of transplanted cells.
to transition iPS to clinical applications, reducing the time it takes to differentiate these cells into the required cells and the costs associated with building, maintaining and using iPS cell culture for therapeutic purposes are key.
When iPSC differentiated neurons, less protrusive glial cells, or astrological glial cells were used as cell products for central nervous system diseases, proliferation differences, differentiation of non-homogeneity, and different genetic backgrounds were technical barriers.
reported that the gene expression of iPSC-based dopamine-energy neurons in PD patients was significantly different from that of proto-dopamine neurons.
, genetic changes in iPSCs from patients with the body, reactions to drugs, and cell age limit their therapeutic potential compared to iPSCs from allogeneic health providers.
iPSC is also facing tumor-caused problems and ethical controversy, which involves their infinite ability to differentiate, and there are concerns that these cells could one day be used in human cloning.
4.4 Stem Cell Therapy Trial Evaluation Current clinical trials use different methods to evaluate the safety and effectiveness of stem cell therapy, and differences in clinical trial design make it difficult to compare results between studies.
a uniform standard for assessing the quality of stem cells.
, summary Stem cell therapy is increasingly becoming a viable treatment, and despite many challenges, the likelihood of stem cell applications increases with each study.
, stem cell therapy is progressing rapidly in neurodegenerative diseases and macular degeneration.
induced erythromatic stem cells are being used in stem cell research, with unlimited possibilities for treating diseases using the patient's own cells.
the use of interstate stem cells to regenerate teeth and periodont tissue has entered the clinic and will soon become an effective treatment.
are working to establish regulatory guidelines and standards around the world to ensure patient safety.
in the near future, stem cell therapy will have a significant impact on human health.
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