RESUMO
The donor-recipient sex-related mismatch has been reported as a risk factor for acute graft-versus-host disease (GVHD). However, the results obtained in previous studies appear to be contradictory. Here we evaluate the impact of donor-recipient sex-related mismatch in a series of 204 Sardinian individuals (92.1% of them affected by Beta- Thalassemia major) who underwent bone marrow transplantation (BMT) from human leukocyte antigen (HLA) identical siblings. In all, 78 of these patients had acute GVHD (aGVHD). We found that also in this homogenous group of patients from a homogenous population, the donor-female/recipient-male pair provided an increased risk for aGVHD when compared with a reference donor-male/recipient-male pair (POR=2.3, P=0.042). This data could be consistent with a role of variation in the male-specific portion of the Y chromosome in aGVHD. To assess this, we compared the distribution of the main Y-chromosome haplogroups in 28 male patients, who had aGVHD and underwent BMT from HLA-identical sisters, and 366 ethnically-matched controls. No significant differences were observed. These findings do not support the presence of Y chromosome founder variants contributing significantly to aGVHD in the Sardinian population.
Assuntos
Cromossomos Humanos Y/genética , Variação Genética , Doença Enxerto-Hospedeiro/genética , Haplótipos , Histocompatibilidade/genética , Doença Aguda , Adolescente , Adulto , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Efeito Fundador , Antígenos HLA/imunologia , Humanos , Lactente , Itália , Masculino , Talassemia beta/cirurgiaRESUMO
BACKGROUND: It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. RESULTS: In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC). Cells were treated with: (1) TPA, forskolin, IBMX, FGF-1 or (2) retinoic acid and 2-mercaptoethanol (BME). Treatment (1) induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1) compared with treatment (2). In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. CONCLUSION: Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.
Assuntos
Células da Medula Óssea/citologia , Diferenciação Celular/fisiologia , Neurônios/fisiologia , Células-Tronco/fisiologia , 1-Metil-3-Isobutilxantina/farmacologia , Adolescente , Adulto , Antígenos CD/metabolismo , Western Blotting/métodos , Células da Medula Óssea/fisiologia , Diferenciação Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Criança , Colforsina/farmacologia , Fator 1 de Crescimento de Fibroblastos/farmacologia , Citometria de Fluxo/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica/métodos , Proteínas de Filamentos Intermediários/metabolismo , Mercaptoetanol/farmacologia , Microscopia Eletrônica de Varredura/métodos , Proteínas do Tecido Nervoso/metabolismo , Nestina , Proteínas de Neurofilamentos/metabolismo , Neurônios/ultraestrutura , Fenótipo , Inibidores de Fosfodiesterase/farmacologia , Fosfopiruvato Hidratase/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Células-Tronco/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Tretinoína/farmacologiaRESUMO
Stem-cell transplantation can cure beta thalassaemia. We aimed to assess whether fetal HLA typing done early in the pregnancy of couples who were at risk of beta thalassaemia could provide an alternative to pregnancy termination if the prospect of a bone-marrow transplantation from a family member was available. In our clinic in Sardinia, we did fetal HLA typing for 49 couples at risk of having a baby with beta thalassaemia. Two affected children were born and successfully received a transplantation from a family donor. Five non-affected fetuses were HLA compatible with an affected sibling and their cord blood was harvested for a future transplantation.
Assuntos
Doenças Fetais/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Talassemia beta/imunologia , Talassemia beta/terapia , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Aconselhamento Genético , Teste de Histocompatibilidade/ética , Humanos , Diagnóstico Pré-Natal/ética , Fatores de Risco , Irmãos , Talassemia beta/diagnósticoRESUMO
It has recently been reported that adult hematopoietic stem cells can differentiate into neural cells, opening new frontiers in therapy for neurodegenerative diseases. In this study, adult human hematopoietic stem cells (HSCs) were isolated via magnetic bead sorting, using a specific CD34 antibody and cultured with human astrocyte culture conditioned medium (ACM). In order to evaluate their differentiation into neurons and/or astrocytes, ACM-treated cultures were probed for the expression of several neural markers. We observed morphological modifications and, after 20 days of treatment, cell morphology displayed extending processes. Immunocytochemistry, Western blotting and RT-PCR showed the expression of neuronal markers such as neurofilaments, neuron specific enolase (NSE) and NeuN in ACM-treated HSCs cultured in poly-L-lysine-coated dishes. On the contrary, when the same ACM-treated cells were grown on a plastic substrate, they expressed high levels of glial fibrillary acidic protein (GFAP), with only weak expression of neuronal markers. Nestin, a neural progenitor cell marker, was present in treated cells, regardless of the substrate. These results demonstrate that astrocytes can generate a suitable microenvironment for inducing HSCs to differentiate into neural cells. Therefore, adult bone marrow may represent a readily accessible source of cells for treating neurodegenerative diseases.