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Braz. arch. biol. technol ; 64: e21180392, 2021. graf
Article in English | LILACS | ID: biblio-1249216


ABSTRACT The therapeutic effect of adipose tissue-derived stem cells (ADSCs) or RE on hippocampal neurogenesis and memory in Parkinsonian rats were investigated. Male rats were lesioned by bilateral intra-nigral injections of 6-OHDA and divided into six groups: 1. Lesion 2 and 3: RE and water groups were lesioned rats pretreated with RE or water, from 2weeks before neurotoxin injection and treated once a day for 8weeks post lesion. 4&5: Cell and α-MEM (α-minimal essential médium) received intravenous injection of BrdU-labeled ADSCs or medium, respectively from 10days post lesion until 8weeks later. 6: Sham was injected by saline instead of neurotoxin. Memory was assessed using Morris water Maze (MWM), one week before and at 1, 4 and 8weeks post 6-OHDA lesion. After the last probe, the animals were sacrificed and brain tissue obtained. Paraffin sections were stained using cresyl violet, anti-BrdU (Bromodeoxyuridine / 5-bromo-2'-deoxyuridine), anti-GFAP (Glial fibrillary acidic protein) and anti-TH antibodies. There was a significant difference of time spent in the target quadrant between groups during probe trial at 4 and 8 weeks' post- lesion. Cell and RE groups spent a significantly longer period in the target quadrant and had lower latency as compared with lesion. Treated groups have a significantly higher neuronal density in hippocampus compared to water, α-MEM and lesion groups. BrdU positive cells were presented in lesioned sites. The GFAP (Glial fibrillary acidic protein) positive cells were reduced in treated and sham groups compared to the water, α-MEM and lesion groups. Oral administration of RE (Rosemary extract) or ADSCs injection could improve memory deficit in the Parkinsonian rat by neuroprotection.

Parkinson Disease/physiopathology , Rosmarinus , Stem Cell Transplantation , Memory Disorders/therapy , Morris Water Maze Test , Hippocampus
Chinese Medical Journal ; (24): 1199-1208, 2021.
Article in English | WPRIM | ID: wpr-878101


BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

B-Lymphocytes , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Recurrence , Retrospective Studies , Risk Factors , Stem Cell Transplantation
Estud. Interdiscip. Psicol ; 11(2): 167-197, maio-ago.2020. Tab
Article in Portuguese | LILACS | ID: biblio-1342145


Este estudo teve por objetivo conhecer as percepções e vivências do acompanhante familiar diante do adoecer e do transplante de células-tronco hematopoéticas (TCTH) à luz da teoria do luto antecipatório. Trata-se de um estudo exploratório com abordagem qualitativa, do qual participaram 11 familiares. As entrevistas individuais foram organizadas pela análise temática e interpretados em três níveis contextuais, envolvendo mudanças intrapsíquicas, interacionais com o paciente e no âmbito familiar/social. Constatou-se que o familiar experimenta sentimentos e reações emocionais consistentes com o processo de enlutamento. As mudanças na interação com o paciente acontecem desde os primeiros sintomas e intensificam-se com a necessidade de fornecer cuidado integral na enfermaria durante o transplante. Transformações na dinâmica familiar acontecem em resposta às perdas de papéis sociais, ocupacionais e seus impactos financeiros. Ademais, o sofrimento experimentado pelo cuidador durante esse processo não é legitimado, tanto pela família quanto pela equipe de saúde, já que do acompanhante se exige que seja uma fonte de apoio inabalável (AU).

This study aimed to know the perceptions and experiences of family companions facing illness and transplantation of hematopoietic stem cells (HSCT) in light of the theory of anticipatory grief. This is an exploratory study with a qualitative approach, in which 11 relatives participated. The individual interviews were organized by thematic analysis and interpreted at three contextual levels, involving intra-psychic, interactional with the patient and family / social changes. It was found that the family member experiences feelings and emotional reactions consistent with the bereavement process. Changes in patient interaction occur from the earliest symptoms and intensify with the need to provide comprehensive nursing care during transplantation. Transformations in family dynamics occur in response to the loss of social, occupational roles and their financial impacts. Moreover, the suffering experienced by the caregiver during this process is not validated, either by the family or by the healthcare providers, as the companion is required to be an unshakable source of support (AU).

Este estudio tuvo como objetivo conocer las percepciones y experiencias del compañero familiar cuando se enfrenta a una enfermedad y el trasplante de células madre hematopoyéticas (TCMH) a la luz de la teoría del duelo anticipatorio. Este es un estudio exploratorio con un enfoque cualitativo, en el que participaron 11 familiares. Las entrevistas individuales fueron organizadas por análisis temático e interpretadas en tres niveles contextuales, involucrando intrapsíquica, interacción con el paciente y cambios familiares / sociales. Se descubrió que el miembro de la familia experimenta sentimientos y reacciones emocionales consistentes con el proceso de duelo. Los cambios en la interacción con el paciente ocurren desde los primeros síntomas y se intensifican con la necesidad de proporcionar atención integral de enfermería durante el trasplante. Las transformaciones en la dinámica familiar ocurren en respuesta a la pérdida de roles sociales, ocupacionales y sus impactos financieros. Además, el sufrimiento experimentado por el cuidador durante este proceso no está legitimado, ni por la familia ni por el equipo de salud, ya que el acompañante debe ser una fuente de apoyo inquebrantable (AU).

Humans , Male , Female , Hematopoietic Stem Cells , Bereavement , Family , Caregivers , Stem Cell Transplantation , Emotions , Grief
Autops. Case Rep ; 10(2): e2020147, Apr.-June 2020. graf
Article in English | LILACS | ID: biblio-1131811


In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.

Humans , Female , Adolescent , Stem Cell Transplantation/adverse effects , Blood Cell Count , Hematopoietic Stem Cells , B-Lymphocytes/cytology , B-Lymphocyte Subsets/pathology , Flow Cytometry , Anemia, Sickle Cell , Lymphoproliferative Disorders/diagnosis
Arq. bras. oftalmol ; 83(2): 160-167, Mar.-Apr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088965


ABSTRACT Degenerative retinal diseases such as retinitis pigmentosa, Stargardt's macular dystrophy, and age-related macular degeneration are characterized by irreversible loss of vision due to direct or indirect photoreceptor damage. No effective treatments exist, but stem cell studies have shown promising results. Our aim with this review was to describe the types of stem cells that are under study, their effects, and the main clinical trials involving them.

RESUMO As doenças degenerativas da retina, como retinose pigmentar, distrofia macular de Stargardt e degeneração macular relaciona à idade, são caracterizadas por perda irre versível da visão devido a danos diretos ou indiretos aos fotorreceptores. Não existem tratamentos eficazes, porém os estudos com células-tronco mostraram resultados promissores. Nosso objetivo com esta revisão foi descrever os tipos de células-tronco em estudo, seus efeitos e os principais ensaios clínicos que as envolvem.

Humans , Retinal Degeneration/therapy , Pluripotent Stem Cells/transplantation , Stem Cell Transplantation/methods , Retina/cytology , Clinical Trials as Topic , Treatment Outcome
Braz. j. med. biol. res ; 53(11): e9728, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132496


The aim of this study was to propose a stem cell therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) based on plasma exchange (PE) for peripheral blood stem cell (PBSC) collection and examine its safety and efficacy. Sixty patients (n=20 in each group) were randomized to PE (PE alone), granulocyte colony-stimulating factor (G-CSF) (PE after G-CSF treatment), and PBSC transplantation (PBSCT) (G-CSF, PE, PBSC collection and hepatic artery injection) groups. Patients were followed-up for 24 weeks. Liver function and adverse events were recorded. Survival analysis was performed. PBSCT improved blood ammonia levels at 1 week (P<0.05). The level of total bilirubin, international normalized ratio, and creatinine showed significant differences in the 4th week of treatment (P<0.05). The survival rates of the PE, G-CSF, and PBSCT groups were 50, 65, and 85% at 90 days (P=0.034). There was a significant difference in 90-day survival between the PE and PBSCT groups (P=0.021). The preliminary results suggested that PBSCT was safe, with a possibility of improved 90-day survival in patients with HBV-ACLF.

Humans , Male , Female , Adult , Middle Aged , Hepatitis B virus , Granulocyte Colony-Stimulating Factor , Hepatitis B/complications , Plasma Exchange , Stem Cell Transplantation
Article in English | WPRIM | ID: wpr-786216


Therapeutic angiogenesis is an important strategy to rescue ischemic tissues in patients with critical limb ischemia having no other treatment option such as endovascular angioplasty or bypass surgery. Studies indicated so far possibilities of therapeutic angiogenesis using autologous bone marrow mononuclear cells, CD34⁺ cells, peripheral blood mononuclear cells, adipose-derived stem/progenitor cells, and etc. Recent studies indicated that subcutaneous adipose tissue contains stem/progenitor cells that can give rise to several mesenchymal lineage cells. Moreover, these mesenchymal progenitor cells release a variety of angiogenic growth factors including vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor and chemokine stromal cell-derived factor-1. Subcutaneous adipose tissues can be harvested by less invasive technique. These biological properties of adipose-derived regenerative cells (ADRCs) implicate that autologous subcutaneous adipose tissue would be a useful cell source for therapeutic angiogenesis in humans. In this review, I would like to discuss biological properties and future perspective of ADRCs-mediated therapeutic angiogenesis.

Angioplasty , Bone Marrow , Extremities , Fibroblast Growth Factors , Hepatocyte Growth Factor , Humans , Intercellular Signaling Peptides and Proteins , Ischemia , Mesenchymal Stem Cells , Stem Cell Transplantation , Stem Cells , Subcutaneous Fat , Vascular Endothelial Growth Factor A
Journal of Experimental Hematology ; (6): 1429-1432, 2020.
Article in Chinese | WPRIM | ID: wpr-827099


Acute myeloid leukemia (AML) is a kind of malignant hematological disease with high mortality. Patients 5-year survival rate is less than 25% and that of elderly patients is lower than 10%. Although the standardized chemotherapy or hematopoetic stem cell transplantation can significantly improve the therapeutic efficacy for AML, but disease recurrence is still a difficult problem in most patients. Chemotherapy combined with immunotherapy has been regarded as the most promising treatment for AML in recent years, but immunotherapy is prone to immune escape, which has become an important factor affecting the therapeutic efficacy. Therefore, understanding the mechanism of immune escape of AML and taking corresponding measures in time to improve the therapeutic effect and reduce the recurrence of AML are of great significance. In this review, the important cells that cause immune escape, such as myeloid-derived suppressor cells (MDSC), natural killer cells (NK), and cell surface inhibitory receptor PD-1 (programmed death 1), which mediate immune escape of AML cells are summarized, so as to provide valuable reference for research to improve the effect of AML immunotherapy.

Aged , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy , Killer Cells, Natural , Leukemia, Myeloid, Acute , Stem Cell Transplantation
Belo Horizonte; s.n; 2020. 86 p. ilus, tab.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1284535


Este estudo objetivou avaliar a experiência de cárie dentária e fatores associados, em indivíduos de transplante de células tronco hematopoiéticas, fígado e rim. Avaliou-se também o impacto da saúde bucal na qualidade de vida desses indivíduos e sua associação com a experiência de cárie e fluxo salivar. Um estudo transversal analítico controlado, com 40 indivíduos de transplante e 40 controles não indicados ao transplante, pareados por idade e sexo, atendidos na Faculdade de Odontologia da UFMG (Brasil) foi conduzido. Dados sociodemográficos e econômicos, medicações em uso e tempo de pós-transplante foram coletados. Avaliou-se a experiência de cárie pelos índices CPOS e COR (superfície). O impacto da saúde bucal na qualidade de vida foi mensurado pelo instrumento Oral Health Impact Profile (OHIP-14). Coletou-se saliva para obtenção do fluxo, pH, composição química e capacidade tampão. Avaliou-se a ingestão de açúcares livres pelo recordatório de 24 horas. A análise de regressão mostrou que o aumento de um indivíduo morador na casa do paciente aumenta as chances de ter alta experiência de cárie (OR = 1,35; IC95% 1,02-1,79). O aumento de um ponto do fluxo salivar diminuiu as chances de alta experiência de cárie dentária (OR = 0,14; IC95% 0,03-0,72). Quanto ao impacto da saúde bucal na qualidade de vida, os indivíduos em condição de transplante de fígado apresentaram valores significativamente maiores de medianas (4,0 [0-7,0]) comparados aos de transplante de rim (0,5 [0-5]) (p=0,043), para o domínio desconforto psicológico. As medianas do número de superfícies perdidas foram significativamente maiores nos indivíduos de transplante de fígado (45,0 [0-81,0]), comparados aos de rim (12,0 [0-65,0]) (p=0,045). Os indivíduos de transplante de rim (32,5 [1,0-58,0]) apresentaram número de superfícies restauradas significativamente maiores, comparados aos de fígado (13,0 [0-32,0]) (p=0,049). A faixa etária entre 56 e 61 anos (13,0 [7,0-25,0]) apresentou maiores valores do OHIP- 14, comparada à faixa de 25 a 40 anos (4,5 [0-29,0]) (p=0,013). Os valores de OHIP-14 apresentaram correlação positiva moderada significativa, com o número de superfícies dentárias perdidas (ρ=0,433; p=0,005). Não houve correlação entre o valor de OHIP-14 e o fluxo salivar. Concluiu-se que o aumento do fluxo salivar diminuiu as chances de o indivíduo apresentar uma alta experiência de cárie. O aumento do número de indivíduos moradores da casa aumentou as chances de ocorrência de alta experiência de cárie. Indivíduos de transplante de fígado apresentaram maior desconforto psicológico e um maior número de superfícies dentárias perdidas, comparados aos de transplante renal. A maior perda dentária foi correlacionada com um pior impacto da saúde bucal na qualidade de vida dos indivíduos de transplante. Indivíduos a partir de 56 anos de idade demonstraram um maior impacto na qualidade de vida relacionada à saúde bucal.

The aim of this study was evaluate the experience of tooth decay and associated factors in hematopoietic stem cell, liver and kidney transplant patients. The impact of oral health on the quality of life of these individuals and its association with the experience of caries and salivary flow were also evaluated. A controlled analytical cross-sectional study with 40 transplant individuals and 40 controls not indicated for transplantation, matched for age and sex, attended at the UFMG School of Dentistry (Brazil) was conducted. Sociodemographic and economic data, medications in use and post-transplant time were collected. The caries experience was evaluated using the CPOS and COR (surface) indexes. The impact of oral health on quality of life was measured using the Oral Health Impact Profile (OHIP-14). Saliva was collected to obtain flow, pH, chemical composition and buffering capacity. The intake of free sugars was evaluated by the 24-hour recall. The regression analysis showed that the increase of an individual living in the patient's home increases the chances of having a high caries experience (OR =1.35; 95% CI 1.02-1.79). The increase of one point in the salivary flow decreased the chances of high experience of dental caries (OR=0.14; 95% CI 0.03-0.72). As for the impact of oral health on quality of life, individuals in conditions of liver transplantation had significantly higher median values (4.0 [0-7.0]) compared to those of kidney transplantation (0.5 [0- 5]) (p = 0.043), for the psychological discomfort domain. The medians of the number of surfaces lost were significantly higher in the liver transplant subjects (45.0 [0-81.0]), compared to the kidney (12.0 [0-65.0]) (p = 0.045). The kidney transplant individuals (32.5 [1.0-58.0]) had significantly higher number of restored surfaces, compared to the liver (13.0 [0-32.0]) (p = 0.049). The age group between 56 and 61 years old (13.0 [7.0-25.0]) presented higher OHIP-14 values, compared to the age group from 25 to 40 years old (4.5 [0-29.0]) (p=0.013). The OHIP-14 values showed a significant moderate positive correlation, with the number of missing dental surfaces (ρ = 0.433; p = 0.005). There was no correlation between the OHIP-14 value and the salivary flow. It was concluded that the increase in salivary flow decreased the chances of the individual having a high experience of caries. The increase in the number of individuals living in the home increased the chances of high caries experience. Individuals with liver transplantation had greater psychological discomfort and a greater number of missing dental surfaces, compared to those of kidney transplantation. The greater tooth loss was correlated with a worse impact of oral health on the quality of life of transplant individuals. Individuals over 56 years of age demonstrated a greater impact on quality of life related to oral health.

Quality of Life , Oral Health , Dental Caries , Stem Cell Transplantation/adverse effects , Transplant Recipients , Salivation , Cross-Sectional Studies
Article in English | WPRIM | ID: wpr-810958


BACKGROUND: This study aimed to assess the outcome of stem cell transplantation (SCT), including overall survival (OS), failure-free survival (FFS) and graft-versus-host disease (GvHD)-free/failure-free survival (GFFS), and to analyze prognostic factors in children with aplastic anemia (AA).METHODS: From 1991 to 2018, 43 allogeneic SCT recipients were enrolled in the study to investigate the demographic characteristics, survival outcomes and prognostic factors.RESULTS: With the median follow-up of 7.1 years, the estimated 10-year OS, FFS, GFFS were 86.0%, 60.5%, and 51.2%, respectively. Matched related donors (MRD, n = 28) showed better 10-year OS than unrelated donors (n = 15) (96.4% vs. 66.7%; P = 0.006). Engraftment failure was seen in 13 patients (30.2%). Donor-type aplasia was seen in 13.8% (4/29) after fludarabine (Flu)-based conditioning (Flu-group), while in 42.6% (6/14) after cyclophosphamide (Cy)-based regimen (Cy-group) (P = 0.035). Six patients died. The 10-year OS in Cy-group was 92.9% (n = 14, all MRD), while that of Flu-group was 82.1% (n = 29; P = 0.367). But Flu-group tended to have better FFS and GFFS than Cy-group, although Flu-group had less MRDs (41.4% vs. 100%; P = 0.019), and higher proportion of previous immunosuppressive treatment (IST; 62% vs. 21.4%, P = 0.012). In MRD transplants, OS was similar between Flu-group (100%, n = 14) and Cy-group (92.9%, n = 14), while FFS (100.0% vs. 42.9%; P = 0.001) and GFFS (85.7% vs. 35.7%; P = 0.006) were significantly better in Flu-group. Stem cell sources, irradiation in the conditioning, and method of GvHD prophylaxis did not significantly influence the outcome.CONCLUSION: This study reviewed SCT outcomes for pediatric AA with changes of transplant strategies over the last 25 years. The FFS and GFFS were higher in Flu-group than in Cy-group, especially in matched related transplantation. Graft failure including donor-type aplasia remains troublesome even with Flu-based conditioning. Further refinement of transplant strategies to ensure better quality-of-life should be pursued.

Anemia, Aplastic , Child , Cyclophosphamide , Follow-Up Studies , Graft vs Host Disease , Humans , Methods , Stem Cell Transplantation , Stem Cells , Tissue Donors , Transplants , Unrelated Donors
Blood Research ; : 57-61, 2020.
Article in English | WPRIM | ID: wpr-820802


BACKGROUND: Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging.METHODS: We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37).RESULTS: Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib.CONCLUSION: Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

Delivery of Health Care , Disease Progression , Disease-Free Survival , Humans , Lymphoma, Mantle-Cell , Recurrence , Stem Cell Transplantation , Stem Cells , Veterans
Braz. j. otorhinolaryngol. (Impr.) ; 85(4): 520-529, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019587


Abstract Introduction: Mammalian hair cells and auditory neurons do not show regenerative capacity. Hence, damage to these cell types is permanent and leads to hearing loss. However, there is no treatment that re-establishes auditory function. Regenerative therapies using stem cells represent a promising alternative. Objective: This article aims to review the current literature about the main types of stem cells with potential for application in cell therapy for sensorineural hearing loss, the most relevant experiments already performed in animals, as well as the advances that have been recently made in the field. Methods: Research included the databases PubMed/MEDLINE, Web of Science, Science Direct and SciELO, as well as gray literature. Search strategy included the following main terms: "stem cells", "hair cells" and "auditory neurons". Additionally, the main terms were combined with the following secondary terms: "mesenchymal", "iPS", "inner ear", "auditory". The research was conducted independently by three researchers. Results: Differentiation of stem cells into hair cells and auditory neurons has a high success rate, reaching up to 82% for the first and 100% for the latter. Remarkably, these differentiated cells are able to interact with hair cells and auditory neurons of cochlear explants through formation of new synapses. When transplanted into the cochlea of animals with hearing loss, auditory restoration has been documented to date only in deafferented animals. Conclusion: Advances have been more prominent in cases of auditory neuropathy, since partial improvement of auditory nerve conditions through cell-based therapy may increase the number of patients who can successfully receive cochlear implants.

Resumo Introdução: Nos mamíferos, as células ciliadas e os neurônios auditivos não apresentam capacidade regenerativa. Assim, os danos a esses tipos celulares são permanentes e levam à perda auditiva. Contudo, como não há tratamento que restabeleça a função auditiva, as terapias regenerativas utilizando células-tronco representam uma alternativa promissora. Objetivo: Este artigo tem como objetivo revisar a literatura atual sobre os principais tipos de células-tronco com potencial para aplicação em terapia celular para perda auditiva sensorioneural, os experimentos mais relevantes já realizados em animais, bem como os avanços obtidos recentemente nessa área. Método: As pesquisas incluíram as bases de dados PubMed/MEDLINE, Web of Science, Science Direct e SciELO, além da literatura cinza. A estratégia de busca incluiu os seguintes termos principais: "stem cells", "hair cells" e "auditory neurons". Além disso, os termos principais foram combinados com os seguintes termos secundários: "mesenchymal", "iPS", "inner ear" e "auditory". A pesquisa foi realizada de forma independente por três pesquisadores. Resultados: A diferenciação de células-tronco em células ciliadas e neurônios auditivos têm alta taxa de sucesso, chegando a 82% para o primeiro caso e 100% para o segundo. Notavelmente, essas células diferenciadas são capazes de interagir com células ciliadas e neurônios auditivos de explantes cocleares através da formação de novas sinapses. Quando transplantadas para a cóclea de animais com perda auditiva, a restauração da função auditiva foi observada, até o momento, apenas em animais com ablação do VIII nervo craniano. Conclusão: Os avanços têm sido mais proeminentes em casos de neuropatia auditiva. A melhora parcial das condições do nervo auditivo por meio de terapia baseada em células-tronco pode aumentar o número de pacientes candidatos a receber implantes cocleares com sucesso.

Humans , Animals , Stem Cell Transplantation , Hearing Loss, Sensorineural/therapy , Cell Differentiation , Cochlear Nerve/cytology , Hair Cells, Auditory
Arq. bras. med. vet. zootec. (Online) ; 71(3): 917-928, May-June 2019. ilus
Article in English | ID: biblio-1011332


In veterinary medicine, the cell therapy is still unexplored and there are many unanswered questions that researchers tend to extrapolate to humans in an attempt to treat certain injuries. Investigating this subject in nonhuman primates turns out to be an unparalleled opportunity to better understand the dynamics of stem cells against some diseases. Thus, we aimed to compare the efficiency of bone marrow mononuclear cells (BMMCs) and mesenchymal stem cells (MSCs) from adipose tissue of Chlorocebus aethiops in induced bone injury. Ten animals were used, male adults subjected, to bone injury the iliac crests. The MSCs were isolated by and cultured. In an autologous manner, the BMMCs were infused in the right iliac crest, and MSCs from adipose tissue in the left iliac crest. After 4.8 months, the right iliac crests fully reconstructed, while left iliac crest continued to have obvious bone defects for up to 5.8 months after cell infusion. The best option for treatment of injuries with bone tissue loss in old world primates is to use autologous MSCs from adipose tissue, suggesting we can extrapolate the results to humans, since there is phylogenetic proximity between species.(AU)

Na medicina veterinária, a terapia celular ainda é inexplorada e há muitas perguntas não respondidas, o que leva os pesquisadores a uma tendência a estender a terapia para os seres humanos, na tentativa de tratar certas lesões. Investigar esse assunto em primatas não humanos revela-se uma oportunidade sem precedentes para compreender melhor a dinâmica das células-tronco contra algumas doenças. Assim, objetivou-se comparar a eficiência das células mononucleares de medula óssea (BMMCs) e das células-tronco mesenquimais (MSCs) do tecido adiposo de Chlorocebus aetiops na lesão óssea induzida. Foram utilizados 10 animais, adultos do sexo masculino, submetidos à lesão óssea nas cristas ilíacas. As MSCs foram isoladas e cultivadas; de forma autóloga, as BMMCs foram infundidas na crista ilíaca direita e as MSCs de tecido adiposo na crista ilíaca esquerda. Após 4,8 meses, a crista ilíaca direita foi totalmente reconstruída, enquanto a crista ilíaca esquerda continuou apresentando defeito ósseo evidente por até 5,8 meses após a infusão. A melhor opção para o tratamento de lesões com perda de tecido ósseo em primatas do Velho Mundo é a utilização de MSCs autólogas de tecido adiposo, sugerindo que se podem estender os resultados para seres humanos, uma vez que há proximidade filogenética entre as espécies.(AU)

Animals , Male , Bone Marrow Cells , Stem Cell Transplantation/veterinary , Mesenchymal Stem Cells , Cell- and Tissue-Based Therapy/veterinary , Chlorocebus aethiops , Models, Animal , Ilium/injuries
Rev. méd. Chile ; 147(6): 787-789, jun. 2019.
Article in Spanish | LILACS | ID: biblio-1020727


Heart failure is one of the first diseases in which stem cells were used for regenerative medicine. Since 2001, many publications have shown that stem cell therapy has the potential to mitigate heart diseases, but there is no solid scientific evidence to fully support its clinical application at present. The future of regenerative medicine requires validated clinical trials with standardized platforms and transdisciplinary efforts to enable the development of safe and effective regenerative therapies to protect patients and to promote the ethical application of this new and highly promising therapy. Doctors and scientists have a responsibility to discuss with patients the current reality of regenerative therapies. They also have a responsibility to discourage the indiscriminate and commercial use of these therapies, which are sometimes based on false hopes, since their inappropriate use can harm vulnerable patients as well as research efforts. Although regenerative medicine may be the medicine of the future and might bring the hope of cure for chronic diseases, it is not yet ready for its wide clinical application.

Humans , Stem Cell Transplantation/ethics , Heart Failure/therapy , Stem Cell Transplantation/trends , Regenerative Medicine/trends , Regenerative Medicine/ethics
Frontiers of Medicine ; (4): 152-159, 2019.
Article in English | WPRIM | ID: wpr-771306


The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication, articulation, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.

Adult Stem Cells , Physiology , Animals , Cell Differentiation , Humans , Stem Cell Transplantation , Tissue Engineering , Tooth , Cell Biology , Physiology , Wound Healing
Journal of Experimental Hematology ; (6): 1330-1333, 2019.
Article in Chinese | WPRIM | ID: wpr-775719


Abstract  Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, high risk of transformation from MDS into AML. Allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, but the failure rate of transplantation is still high, which attribute to relapsed disease and transplant-related complications. Recently, the spectrum of gene abnormalities in MDS has been revealed by next generation genomic sequencing techniques. It was found that more than 80% MDS patients have at least one gene mutation. Mutated genes in MDS are powerfully associated with clinical phenotype and prognosis. In this review , the recent advancements regarding recurrent gene mutations in MDS are briefly summarized, and the  prognostic values of gene mutations are discussed in MDS or after allogeneic hematopoietic stem-cell transplantation,so as to set up a predicting model and to guide the treatment.

Hematopoietic Stem Cell Transplantation , Humans , Mutation , Myelodysplastic Syndromes , Prognosis , Stem Cell Transplantation
Chonnam Medical Journal ; : 25-30, 2019.
Article in English | WPRIM | ID: wpr-719479


This study investigated the efficacy and safety of melphalan, cyclophosphamide, and dexamethasone (MCD) as a salvage regimen for heavily treated relapsed or refractory multiple myeloma patients. We retrospectively analyzed a total of 27 patients who received the MCD regimen between April 2011 and November 2013. The MCD regimen consisted of oral melphalan 6.75 mg/m² on days 1–4, once-weekly dose of oral cyclophosphamide 300 mg/m2 and dexamethasone 20 mg/m² on days 1–4 and days 15–18. Each cycle was repeated every 28 days. The median age of the patients was 66 years and the MCD regimen was initiated at a median 37.7 months from diagnosis. Patients received a median of five regimens including autologous stem cell transplantation. The overall response rate was 25.9% (very good partial response 3.7%, partial response 22.2%) and 8 (29.6%) patients achieved a minor response. Median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2–8.5) ; overall survival 11.7 months (95% CI, 5.4–16.6). Grade 3 or 4 neutropenia and thrombocytopenia were observed in 51.8% and 33.3%, respectively. Although the overall response rate is relatively low, the MCD regimen may have a role as a bridge to a novel regimen in heavily pretreated patients with MM.

Cyclophosphamide , Dexamethasone , Diagnosis , Disease-Free Survival , Humans , Melphalan , Multiple Myeloma , Neutropenia , Retrospective Studies , Salvage Therapy , Stem Cell Transplantation , Thrombocytopenia