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RNA N6-methyladenosine (m6A) regulators are essential for a variety of biological functions, such as early development, viral infections, and cancer. However, their roles in Alzheimer disease (AD) are still not very clear. Here, 16 significant m6A regulators were identified using difference analysis between AD patients and non-demented controls based on the GSE132903 dataset from the Gene Expression Omnibus database. Using these 16 m6A regulators, a nomogram model was established to predict the prevalence of AD. We found that patients could obtain a good clinical benefit based on this model. In addition, we revealed 2 distinct m6A patterns and 2 distinct m6A gene patterns in AD and demonstrated their prognostic and risk assessment significance. This present work comprehensively evaluated the functions of m6A regulators in the diagnosis and subtype classification of AD. These results suggested they have potential prognostic and risk assessment significance in AD.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Adenosina , Bases de Dados Factuais , RNARESUMO
Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has emerged as a potential treatment for ischemic stroke. Preconditioning with pharmacological agents before cell transplantation has been shown to increase the efficiency of cell therapy. In this study, trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the neuroprotective effect of BMSCs preconditioned with Tre on cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre. Immunofluorescence staining of LC3B was performed to detect autophagy, and Western blotting for LC3, Beclin1, p-AMPK, and p-mTOR was performed. Flow cytometry and Western blotting analysis were performed to measure cell apoptosis in the presence of hydrogen peroxide (H2O2). Enzyme-linked immunosorbent assay was used to test the secretion levels of neurotrophic factors. An in vivo ischemia/reperfusion model was generated by middle cerebral artery occlusion in male Sprague Dawley rats, and Tre-preconditioned BMSCs were administered intralesionally 24 hours after ischemic injury. Histopathological examination and neurological function studies were conducted. In vitro, Tre promotes autophagy of BMSCs through the activation of the AMPK signal pathway. Tre protected BMSCs from H2O2-induced cell viability reduction and apoptosis. Moreover, Tre pretreatment increased the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor, and hepatocyte growth factor. In vivo, preconditioning with Tre could further enhance the survival of BMSCs, reduce infarct size, alleviate cell apoptosis, abate vessel decrease, and ultimately improve functional recovery. Our study indicates that Tre can enhance the survival of BMSCs under oxidative stress and enhance BMSC-based treatment of ischemia/reperfusion injury.
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AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Células da Medula Óssea , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Isquemia/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Trealose/metabolismo , Trealose/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Because MSC-NTF has a higher ability to secrete neurotrophic factors, it may have a greater potential than ordinary MSC in clinical applications. At present, research on MSC-NTF mainly focuses on clinical aspects, but its basic research is relatively few. In particular, the research on the comprehensive and detailed characteristics of MSC-NTF is missing. And its in vivo research in animals is also rare. Since the transplantation of human-derived MSC-NTF into rats is cross-species, its survival in the rat and the therapeutic effect may be seriously affected due to severe immune rejection. This will inevitably affect the research on the basic characteristics and the therapeutic mechanisms of MSC-NTF in vivo. Therefore, we chose the rat-derived MSCs to be induced as the MSC-NTF which had a stronger neurotrophic factor secretion function. This will also be helpful to perform the research of the basic therapeutic mechanisms of MSC-NTF in vivo. In addition, we have established some important characteristics that can be used to distinguish between MSC-NTF and MSCs: different multi-factor secretion ability and secretion characteristics, immunogenicity, three-line differentiation ability, stemness, etc. In addition to paying attention to their safety differences, this study also explored the differences in their in vivo survivability. Finally, we applied this newly induced rat-derived MSC-NTF in a rat model of ischemic stroke, and obtained beneficial therapeutic effects.
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AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Modelos Animais de Doenças , Fatores de Crescimento Neural/genética , Ratos , Fator de Crescimento Transformador betaRESUMO
Hepatocellular carcinoma (HCC) is a cancer with extremely high mortality. Epithelial-mesenchymal transition (EMT) may play an important role in the occurrence, invasion and prognosis of HCC; however, its relationship with immunity in HCC has not yet been studied. Therefore, we investigated the diagnostic and prognostic values of EMT and explored its potential connections with tumorigenic immune infiltrates in HCC. We first proposed a quantitative metric of EMT activity, the EMT score. After applying this metric to 20 datasets from the Integrative Molecular Database of Hepatocellular Carcinoma, the Cancer Genome Atlas, and the Gene Expression Omnibus, we explored the ability of the EMT score to stratify across sample types. We then applied the EMT score for survival analysis and to differentiate patients with/without vascular invasion to test its prognostic value. We also collected and calculated data on the abundance of immune cells and immune cell markers in HCC and investigated their correlations with EMT scores. Finally, we synthesized and analyzed 20 datasets and constructed an EMT-gene-immune linkage network. The results showed higher EMT scores in HCC samples than in cirrhotic and normal livers. The cases with higher EMT scores also showed poorer performance in terms of prognostic factors such as vascular invasion and overall survival time. Our research demonstrated a broad correlation between EMT and the tumor immune microenvironment, and we uncovered multiple potential linkers associated with both EMT and immunity. Studying EMT has clinical relevance and high diagnostic and prognostic value for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinogênese , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Prognóstico , Microambiente TumoralRESUMO
Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations was mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by branching into two paths: 1) unipotent preadipocytes or 2) bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of their heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of their functional subpopulations.
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Células-Tronco Mesenquimais , Geleia de Wharton , Diferenciação Celular/genética , Proliferação de Células , Células Cultivadas , TranscriptomaRESUMO
BACKGROUND: Over the last few years, great progress has been made in the development of key technologies to detect peripheral blood-based, tumor-specific biomarkers, such as circulating tumor cells (CTCs) and circulating cell free tumor DNA (ctDNA). Despite the considerable advances and their multiple clinical values, liquid biopsies are challenged by the very low concentrations of CTCs and ctDNA in blood samples. Additionally, blood biomarkers which were found using data-driven methods may only be effective in few datasets. METHODS: We firstly collected the genes which have expression correlations between blood and the other tissues/organs using Genotype-Tissue Expression (GTEx). Survival hazard genes and differential expression genes of each cancer type in The Cancer Genome Atlas (TCGA) were then selected by Cox regression model and Wilcoxon rank sum test, respectively. By combining the P values of two steps, several blood biomarkers can be inferred for each cancer type. After applying these potential blood biomarker sets to 13 datasets of blood samples from solid tumor patients using single sample gene set enrichment analyses (ssGSEA), we got an enrichment score (ES) for each sample. RESULTS: The inferred blood biomarker (BB infer) genes showed reliable predictive value in various malignancies. In all the blood samples that were analyzed, the ESs of positive BB Infer genes in cancer patients are higher than healthy people. Conversely, the ESs of negative BB Infer genes in cancer patients are lower than healthy people. Furthermore, lower ES of negative BB infer genes signify the dismal outcome of patients. CONCLUSIONS: We developed a novel solid tumor blood biomarker inference workflow for cancer screening and diagnosis. Moreover, we demonstrated the utility of this inference method in a series of blood sample datasets of solid tumor patients. These results suggested the potential value of this method in the screening, diagnosis and prognosis of cancers.
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Diffuse glioma is the deadliest form of brain cancer, and the median survival of grade IV glioma (glioblastoma, GBM) is no more than 2 years even with maximal surgical resection followed by radiotherapy and chemotherapy, which are now the standard of care for GBM. Glioma shares common characteristics with most malignant tumours, such as invasiveness, rapid progression, resistance to various therapies and inevitable recurrence, while it also has its own unique features, such as high aggressiveness and immunotherapy resistance, which can be, respectively, attributed to epithelial-mesenchymal transition (EMT) and the immunosuppressive microenvironment. Here, we calculated the EMT score of glioma using The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Omnibus (GEO) datasets and validated its prognostic value. Then, we investigated its role in the glioma immune microenvironment, identified the enriched EMT-related immune genes and determined their specific biological functions in glioma. Furthermore, clinical relevance analysis showed the translational value of these EMT-related immune genes. In short, our findings reveal a critical link between EMT and the glioma immune microenvironment and offer important clues for further investigation of the underlying molecular mechanism.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Transição Epitelial-Mesenquimal , Glioma/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioma/imunologia , Glioma/patologia , Humanos , Proteoma/genética , Proteoma/metabolismo , TranscriptomaRESUMO
BACKGROUND: Our previous studies confirmed that human Wharton's Jelly stem cell (hWJSC) transplantation improved motor function in children with spastic cerebral palsy (CP). This study investigated the dose-effect relationship between the transplanted cell dosage and efficacy in CP children. METHODS: CP children who received one- or two-course (four or eight times lumbar puncture, 4 or 8 × 107 hWJSCs) cell therapy were recruited into this study. Assessments of motor function were performed according to scales for gross motor function measurement (GMFM) and fine motor function measurement (FMFM). The measurement data obtained in the two different groups were analyzed by t-test. Univariate repeated measures analysis of variance was used to compare the data obtained at baseline and 6 or 12 months posttransplantation and met the conditions for Mauchly's sphericity test. RESULTS: The results for fifty-seven pediatric CP patients (including 35 male and 22 female patients) who completed follow-up showed that gross and fine motor functions improved after cell therapy. Interestingly, the GMFM and FMFM scores in patients who received one course of transplantation were significantly increased at 6 months after treatment. Moreover, another course of transplantation further improved gross and fine motor function in children. The scores for GMFM and FMFM were significantly higher at 6 months posttransplantation than at baseline and showed a linear upward trend. There was no gender difference in GMFM. Interestingly, there was a significant difference between male and female patients in the B and C dimensions of FMFM. These results reveal a gender-related susceptibility to stem cell therapy, especially for movement capability of the upper extremity joint and grasping ability. Similarly, in the group aged ≤3 years old, the improvement observed in dimension A (lying and rolling) of GMFM was nearly exponential and showed a quadratic trend. The results for FMFM were similar to those for GMFM. Moreover, the improvement in motor function was not age dependent. CONCLUSIONS: In this study, our data collectively reveal that CP children display sex- or age-dependent responses to hWJSC therapy; these results shed light on the clinical utility of this approach in specific populations.
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AIMS: The objective of this study was to analyze the efficacy of polypyrrole/polylactic acid (PPy/PLA) nanofibrous scaffold cotransplanted with bone marrow stromal cells (BMSCs) in promoting the functional recovery in a rat spinal cord injury (SCI). METHODS: Female Sprague-Dawley rats were randomly divided into three groups (n = 18/group): control group, PPy/PLA group, and PPy/PLA/BMSCs group. The SCI was induced in all rats. Consequently, rats in PPy/PLA/BMSCs group were transplanted with 1 × 105 BMSCs after implantation of PPy/PLA, while those in the PPy/PLA group were implanted with PPy/PLA only; no implantation was performed in the control group. Six weeks after surgery, immunofluorescence microscopy, electron microscope, and polymerase chain reaction (PCR) techniques were performed to assess the changes in the injured spinal cord tissues. RESULTS: Electrophysiology and locomotor function testing suggested that PPy/PLA nanofibrous scaffold cotransplanted with BMSCs could promote the functional recovery of the spinal cord. Six weeks after the operation, lower amount of scar tissue was found in the PPy/PLA group compared with the control group. Abundant neurofilament (NF) and neuron-specific marker (NeuN) positive staining, and myelin formations were detected in the injured area. In addition, the transplantation of BMSCs not only improved the efficacy of PPy/PLA but also managed to survive well and was differentiated into neural and neuroglial cells. CONCLUSIONS: The implantation of PPy/PLA nanofibrous scaffold and BMSCs has a great potential to restore the electrical conduction and to promote functional recovery by inhibiting the scar tissue formation, promoting axon regeneration, and bridging the gap lesion.
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Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Nanofibras/administração & dosagem , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/terapia , Alicerces Teciduais , Animais , Células Cultivadas , Feminino , Poliésteres/administração & dosagem , Polímeros/administração & dosagem , Pirróis/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Spinal cord injury (SCI) involves damage to the central nervous system, and there is no effective treatment available currently. The injured spinal cord is unable to transmit physiological electrical signals caudal to the location of the injury after a complete transection. In this study, we attempted to use a conductive biomaterial as a novel scaffold to aid SCI repair. A composite biomaterial was fabricated by embedding conductive polypyrrole (PPy) in an electrospun polylactic acid (PLA) nanofibrous scaffold (PLA/PPy scaffold), and an electrospun PLA nanofibrous scaffold without the PPy component was used as a control. The scaffolds were implanted into rats having complete T9 spinal cord resection. Immunofluorescent staining, western blot analysis, and TUNEL assay were used to study histological changes in injured spinal cord tissues. Our data demonstrated that PLA/PPy scaffolds had beneficial effects, as evident from the motor evoked-potentials (MEPs) test and Basso, Beattie, and Bresnahan (BBB) locomotion rating scale. Implantation of the PLA/PPy scaffold significantly alleviated secondary tissue damage by reducing apoptosis and autophagy in neural cells in comparison with the implantation of the control PLA scaffold. Notably, six weeks after injury, the use of PLA/PPy scaffolds significantly reduced the activation of astrocytes and increased axonal regeneration, as indicated by immunofluorescent markers (GFAP and NF200) in the region of injury. Our present study suggests that restoring electrical conductivity using a biological scaffold is beneficial to the microenvironment and favorable for the regeneration and functional recovery of spinal cord tissue in an SCI rat model.
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Condutividade Elétrica , Traumatismos da Medula Espinal/terapia , Regeneração da Medula Espinal , Alicerces Teciduais/química , Animais , Apoptose , Astrócitos/fisiologia , Autofagia , Materiais Biocompatíveis/química , Potencial Evocado Motor , Feminino , Nanofibras/química , Polímeros/química , Pirróis/química , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) and bone marrow mononuclear cells (BMMNCs) are both used to treat spastic cerebral palsy. However, the differences in therapeutic effect remain unknown. METHODS: A total of 105 patients with spastic cerebral palsy were enrolled and randomly assigned to three groups: the BMMSC group, the BMMNC group and the control group. Patients in both transplantation groups received four intrathecal cell injections. Patients in the control group received Bobath therapy. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were used to evaluate the therapeutic efficacy before transplantation and 3, 6, and 12 months after transplantation. RESULTS: Three months after cell transplantation, scores in the A dimension of GMFM and the A and C dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). Six months after cell transplantation, scores in the A, B dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are higher than those of the BMMNC and the control groups (P < 0.05). Twelve months after cell transplantation, scores in the A, B, and C dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). No obvious adverse effects were investigated during follow-up. CONCLUSIONS: BMMSC transplantation for the treatment of cerebral palsy is safe and feasible, and can improve gross motor and fine motor function significantly. In addition, compared with BMMNC, the motor function of children improved significantly in terms of gross motor and fine motor functions.
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Paralisia Cerebral/terapia , Leucócitos Mononucleares/transplante , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Paralisia Cerebral/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Atividade MotoraRESUMO
UNLABELLED: Spinal cord injury (SCI) causes a high incidence of motor and sensory dysfunctions accompanied with neuropathic pain. No effective treatment is available. Both somatosensory evoked potential (SSEP) and neuropathic pain (NPP) are transmitted via myelinated large diameter fibers of deep sensory pathways. Here we aimed to evaluate whether SSEP can consistently and objectively assess transmission of deep sensory pathways, and to examine the effects of umbilical cord mesenchymal stem cell (UCMSC) transplantation on SSEP and NPP as assessed by the pain rating index (PRI) in a patient with a 2-year history of complete cervical SCI. We demonstrate that SSEP can directly reflect physiological function of myelinated large fibers in deep sensory pathway transmission (NPP is also transmitted by the same pathway). One year after UCMSC transplantation, the SSEP parameter, PRI, and clinical presentations of NPP significantly improved. KEY WORDS: Spinal cord, neuropathic pain, somatosensory evoked potential, umbilical cord mesenchymal stem cells.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Potenciais Somatossensoriais Evocados/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Neuralgia/terapia , Traumatismos da Medula Espinal/terapia , Adulto , Vértebras Cervicais , Humanos , Masculino , Neuralgia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Resultado do TratamentoRESUMO
Spinal cord injury (SCI) often causes a disturbance in the microenvironment in the lesion site resulting in sudden loss of sensory and motor function. Transplantation of stem cells provides a promising strategy in the treatment of SCI. But limited growth and immunological incompatibility of the stem cells with the host limits the application of this strategy. In order to get better survival and integration with the host, we employed a hyaluronic acid (HA) based scaffold covalently modified by poly-l-Lysine (PLL) as a vehicle to deliver the human bone marrow stromal cells (BMSCs) to the injured spinal cord of rats. The BMSCs were chosen as an ideal candidate for its advantage of low expression of major histocompatibility complex II. The data unexpectedly showed that the hetero-transplanted cells survived well in the lesion site even at 8 weeks post injury. Both the immunofluorescent and the electrophysiological assay indicated better survival of the transplanted cells and improved axonal growth in SCI rats transplanted with BMSCs in HA-PLL in contrast to the groups without either BMSCs or the HA scaffold transplantation. These promotions may account for the functional recovery assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale in the HA-PLL seeded with BMSCs group. These data suggests that hetero-transplantation of human BMSCs delivered by HA scaffold demonstrates a significant role in the functional recovery in the injured spinal cord of rats.
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Hidrogéis , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Traumatismos da Medula Espinal/cirurgia , Alicerces Teciduais , Animais , Astrócitos/metabolismo , Axônios/metabolismo , Axônios/ultraestrutura , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Feminino , Humanos , Ácido Hialurônico , Células-Tronco Mesenquimais/ultraestrutura , Atividade Motora , Neurônios/metabolismo , Neurônios/ultraestrutura , Polilisina/análogos & derivados , Ratos , Ratos Sprague-Dawley , Recuperação de Função FisiológicaRESUMO
BACKGROUND AIMS: The objective of this study was to compare the impact of umbilical cord-derived mesenchymal stromal cell (UCMSC) transplantation on the motor functions of identical twins with cerebral palsy (CP) and to analyze the correlation between the efficacy and hereditary factors. METHODS: Eight pairs (16 individuals) of identical twins with CP were recruited and received allogenic UCMSC transplantation by means of subarachnoid injection. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were performed before and 1 and 6 months after the treatment to analyze the results of individuals before and after the therapy, between two individuals of an identical twin and among twin pairs. Repeated-measured data variance was used to analyze the GMFM and FMFM scores of patients before and 1 and 6 months after the therapy. RESULTS: Eight pairs (16 individuals) of children with CP had significant improvement in the GMFM at the end of the 1st and 6th months after the therapy compared with that before the therapy, whereas the amelioration of the FMFM was not statistically significant. The improvements in motor functions between two individuals of an identical twin but not among twin pairs were correlated. CONCLUSIONS: UCMSC transplantation significantly improves GMFM in children with CP; motor function improvements in the GMFM between two individuals of an identical twin were closely correlated, but improvements among twin pairs were not correlated. We hypothesize that hereditary factors contribute to the mechanisms of UCMSC transplantation in motor function improvement in children with CP.
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Terapia Baseada em Transplante de Células e Tecidos/métodos , Paralisia Cerebral/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Destreza Motora/fisiologia , Paralisia Cerebral/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Projetos Piloto , Gêmeos Monozigóticos , Cordão Umbilical/citologiaRESUMO
BACKGROUND: Umbilical cord mesenchymal stem cells (UCMSCs) have a considerable advantage and potential in treating for central nervous system diseases and have become a novel alternative treatment for spinal cord injury. This study aims to compare the neurological function outcome of stem cell transplantation, rehabilitation therapy, and self-healing for sequelae of spinal cord injury. METHODS: Thirty-four cases of thoracolumbar spinal cord injury were randomly divided into three groups: the stem cell transplantation group was given CT-guided UCMSC transplantation twice; the rehabilitation group received rehabilitation therapy; and the blank control group did not receive any specific treatment. AIS grading, ASIA scoring, the manual muscle strength and muscle tension scale, and the Barthel index were used to evaluate the clinical outcome. Urodynamic examination was also performed for patients in the UCMSC group and the rehabilitation therapy group. RESULTS: Seven of the ten patients in the UCMSC group had significant and stable improvement in movement, self-care ability, and muscular tension; five of the forteen patients (36%) in the rehabilitation group also had certain improvement in these aspects. Urodynamic examination demonstrated that patients in the UCMSC group exhibited an increase in maximum urinary flow rate and maximum bladder capacity, as well as a decrease in residue urine volume and maximum detrusor pressure. The rehabilitation group exhibited decreased maximum bladder capacity, but no perceptible change in maximum urinary flow rate, residue urine volume or maximum detrusor pressure. CONCLUSIONS: UCMSC transplantation can effectively improve neurological functional recovery after spinal cord injury, and its efficacy is superior to that of rehabilitation therapy and self-healing. TRIAL REGISTRATION: The present clinical study was registered at chictr.org (registration number: NCT01393977).
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Vértebras Lombares , Transplante de Células-Tronco Mesenquimais , Traumatismos da Medula Espinal/terapia , Vértebras Torácicas , Cordão Umbilical/citologia , Adulto , Humanos , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/complicaçõesRESUMO
The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 10(5) cells/kg), high dose (2.5 × 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.
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Encéfalo/citologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Animais , Temperatura Corporal , Peso Corporal , Líquido Cefalorraquidiano/citologia , Ingestão de Alimentos , Feminino , Humanos , Imunidade , Inflamação/etiologia , Inflamação/patologia , Macaca fascicularis , Masculino , Necrose/etiologia , Necrose/patologia , Exame Neurológico , Tamanho do ÓrgãoRESUMO
INTRODUCTION: Stem cell therapy has recently been introduced to treat patients with type 2 diabetes mellitus (T2DM). However, no data are available on the efficacy and safety of allogeneic Wharton's Jelly-derived mesenchymal stem cell (WJ-MSC) transplantation in patients with T2DM. Here we performed a non-placebo controlled prospective phase I/II study to determine efficacy and safety of WJ-MSC transplantation in T2DM. METHODS: Twenty-two patients with T2DM were enrolled and received WJ-MSC transplantation through one intravenous injection and one intrapancreatic endovascular injection (catheterization). They were followed up for 12 months after transplantation. The primary endpoints were changes in the levels of glycated hemoglobin and C-peptide and the secondary endpoints included insulin dosage, fasting blood glucose (FBG), post-meal blood glucose (PBG), inflammatory markers and T lymphocyte counts. RESULTS: WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin, improved C-peptide levels and beta cell function, and reduced markers of systemic inflammation and T lymphocyte counts. No major WJ-MSC transplantation-related adverse events occurred, but data suggest a temporary decrease in levels of C-peptide and beta cell function at one month after treatment, possibly related to intrapancreatic endovascular injection. CONCLUSIONS: Our data demonstrate that treatment with WJ-MSCs can improve metabolic control and beta cell function in patients with T2DM. The therapeutic mechanism may involve improvements in systemic inflammation and/or immunological regulation. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-ONC-10000985. Registered 23 September 2010.
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Diabetes Mellitus Tipo 2/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Geleia de Wharton/citologia , Diferenciação Celular/fisiologia , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: This study compared the clinical efficacies, advantages and disadvantages of two transplantation approaches for treating spinal cord injury: open surgical exploration combined with local stem cell transplantation (referred to as open surgical transplantation) and local stem cell transplantation by CT-guided puncture (referred to as CT-guided transplantation). METHODS: The patients were divided into the following three groups to perform a retrospective controlled study: Group A included nine patients who underwent open surgical transplantation, Group B included nine patients who underwent CT-guided transplantation, and Group C included nine patients who did not receive stem cell transplantation. The Abbreviated Injury Scale (AIS), the American Spinal Injury Association (ASIA) score and the motor evoked potentials (MEP) examination were utilized to compare the differences in the clinical efficacies. The advantages and disadvantages of the two transplantation approaches were also compared, including the surgical risks, the possibility of repeating the operation, the interval between surgery and rehabilitation exercises and the scope of conditions suitable for the operation. RESULTS: Whether evaluated by the AIS grading scale, the ASIA score or the MEP results, there were significant differences in the clinical efficacy among the three patient groups. Group B exhibited the best clinical outcome, followed by Group A, and Group C fared the worst. The CT-guided transplantation had the advantages of lower surgical risk, the potential to repeat the operations within a short time-frame and a short interval between surgery and rehabilitation exercise compared with the open surgical transplantation. The conditions that are suitable for CT-guided transplantation versus the conditions suitable for open surgical transplantation are not identical. The application scopes for the two approaches had their respective strengths. CONCLUSIONS: CT-guided stem cell transplantation was confirmed as a safe and effective approach to treat sequelae of spinal cord injury with the advantages of simpler operation, minimal invasion, less adverse reaction and quicker recovery. CLINICAL TRIALS REGISTRATION NUMBER: ChiCTR-TNRC-12002477.
Assuntos
Traumatismos da Medula Espinal/cirurgia , Transplante de Células-Tronco/métodos , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversosRESUMO
BACKGROUND AIMS: Pre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders. METHODS: After providing informed consent, 52 patients with cerebral palsy (CP) who met the study criteria received BM-MSC transplantation. Gross motor function was assessed using the Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before transplantation) and at 1 month, 6 months and 18 months post-transplantation. The participants completed the trial without visible side effects. The GMFM-66 percentile (motor growth curves) was used as the control index of motor function to exclude the interference of improvement with age. RESULTS: The score domains A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased at 1 month, 6 months and 18 months post-transplantation compared with the baseline value (P < 0.01). The scores of domain E also increased at 6 months and 18 months post-transplantation, although they were not significantly increased at 1 month post-transplantation. There were significant increases in the GMFM-66 score and the GMFM-66 percentile corresponding to patient age and Gross Motor Function Classification System level after cell transplantation. CONCLUSIONS: Autologous BM-MSC transplantation appears to be a feasible, safe and effective therapy for patients with CP. The treatment improved the development of children with CP with regard to motor function.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Atividade Motora/fisiologia , Transplante Autólogo , Adolescente , Células da Medula Óssea/citologia , Paralisia Cerebral , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The aim of this study was to investigate the effects of transplantation with umbilical cord mesenchymal stem cells in patients with sequelae of traumatic brain injury (TBI). The study hypothesis was that umbilical cord mesenchymal stem cell transplantation could safely and effectively improve neurological function in patients with sequelae of traumatic brain injury. Forty patients with sequelae of TBI were randomly assigned to the stem cell treatment group or the control group. The patients in the stem cell treatment group underwent 4 stem cell transplantations via lumbar puncture. All patients of the group were also evaluated using Fugl-Meyer Assessments (FMA) and Functional Independence Measures (FIM) before and at 6 months after the stem cell transplantation. The patients in the control group did not receive any medical treatment (i.e., neither surgery nor medical intervention), and their FMA and FIM scores were determined on the day of the visit to the clinic and at 6 months after that clinical observation. The FMA results demonstrated an improvement in upper extremity motor sub-score, lower extremity motor sub-score, sensation sub-score and balance sub-score in the stem cell transplantation group at 6 months after the transplantation (P<0.05). The FIM results also exhibited significant improvement (P<0.05) in the patient self-care sub-score, sphincter control sub-score, mobility sub-score, locomotion sub-score, communication sub-score and social cognition sub-score. The control group exhibited no improvements after 6 months (P>0.05). All in all, the study results confirmed that the umbilical cord mesenchymal stem cell transplantation improved the neurological function and self-care in patients with TBI sequels. Umbilical cord mesenchymal stem cell transplantation may be a potential treatment for patients with sequelae of TBI. Further research, including a multicenter and large sample size prospective randomized clinical trial, will be required to define definitively the role of umbilical cord mesenchymal stem cell transplantation on sequelae of TBI.