ABSTRACT
A tissue stem cell should exhibit long-term self-renewal, clonogenicity and a capacity to differentiate into the tissue of origin. Such a postnatal renal stem cell has not been formally identified. The metanephric mesenchyme (MM) of the developing kidney gives rise to both the renal interstitium and the nephrons and is regarded as the progenitor population of the developing kidney. However, isolated MM does not self renew and requires immortalization for survival in culture. Here we report the isolation and sustained culture of long-term repopulating, clonal progenitors from the embryonic kidney as free floating nephrospheres. Such cells displayed clonal self renewal for in excess of twenty passages when cultured with bFGF and thrombin, showed broad mesodermal multipotentiality, but retained expression of key renal transcription factors (Wt1, Sall1, Eya1, Six1, Six2, Osr1 and Hoxa11). While these cells did display limited capacity to contribute to developing embryonic kidney explants, nephrospheres did not display in vitro renal epithelial capacity. Nephrospheres could be cultured from both Sall1(+) and Sall1(-) fractions of embryonic kidney, suggesting that they were derived from the MM as a whole and not specifically the MM-derived cap mesenchyme committed to nephron formation. This embryonic renal stem cell population was not able to be isolated from postnatal kidney confirming that while the embryonic MM represents a mulitpotent stem cell population, this does not persist after birth.
Subject(s)
Cell Culture Techniques/methods , Cell Proliferation , Embryonic Stem Cells/cytology , Kidney/cytology , Animals , Cells, Cultured , Embryonic Stem Cells/metabolism , Gene Expression , Immunophenotyping , Kidney/immunology , Kidney/metabolism , Mice , Time FactorsABSTRACT
A leucemia promielocítica (LMA M3) representa em média 5-10// dos casos de leucemias melóides agudas (LMA) registrados na literatura, acometendo preferencialmente adultos jovens e cursando com comportamento clínico-biológico distinto, quando comparada com as demais LMA. Caracteriza-se por morfolofia particular das células blásticas (M3 na classificaçäo FAB), translocaçäo dos cromossomos 15 e 17, e coagulaçäo intravascular disseminada ao diagnóstico ou após início da quimioterapia . Dentro deste subgrupo säo observados dois subtipos morfológicos conhecidos como LMA M3 hipergranular e LMA M3 hipogranular ou variante. Os autores analisaram 19 casos de LMA M3, diagnosticados dentre 217 casos de LMA, em seus aspectos clínicos e laboratoriais, e observaram que o reconhecimento da LMA M3 variante, apesar de se basear geralmente apenas em dados citomorfológicos, näo tem sido feito corretamente em nosso meio. Dos oito casos recebidos no serviço dos autores para estudo, apenas quatro foram encaminhados com o diagnóstico correto de seus serviços de origem, sendo os outros quatro casos diagnosticados como leucemia mielomonocítica (LMA M4). A imunofenotipagem, como técnica diagnóstica complementar à citomorfologia, permite esclarecer, definitivamente, casos duvidosos. A classificaçäo correta se faz cada vez mais necessária devido a aspectos terapêuticos e prognósticos particulares das LMA M3, que, ao contrário das outras formas de LMA, têm sido tratadas näo só com drogas citotóxicas, mas também com agentes indutores de diferenciaçäo celular, com excelentes resultados
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Leukemia, Promyelocytic, Acute/pathology , Brazil/epidemiology , Immunophenotyping , Hemorrhage/etiology , Hemorrhage/mortality , Antibodies, Monoclonal , Leukemia, Promyelocytic, Acute/classification , Leukemia, Promyelocytic, Acute/complicationsABSTRACT
Acute promyelocytic leukemia represents 5-10% of acute myeloid leukemia cases (AML) recorded in the literature, occurring more frequently in young adults. It has a special clinical and biological behaviour when compared to the other forms of AML, being characterized by a particular morphology of blast cells (M3 in FAB classification), translocation of chromosomes 15;17, and disseminated intravascular coagulation at diagnosis or after the onset of chemotherapy. Within this AML subgroup there are 2 morphological subsets called the hypergranular promyelocytic leukemia and the hypogranular or variant form. We have studied clinical and laboratory aspects of 19 cases of AML M3 out of 217 AML cases, and observed a high incidence of failure to recognize the M3 variant form, although its diagnosis has been mainly based on cytomorphology. Only 4 out of 8 cases of the variant form received in our laboratory were correctly diagnosed, being the other 4 cases wrongly identified as the myelomonocytic subset of AML (M4). Immunophenotyping with monoclonal antibodies using CD2 and CD7 as T cell markers, CD10 and CD19 as B cell markers and CD33, CD13, CD14, CD15 and anti MPO as myeloid markers is a complementary diagnostic tool that permits solving difficult cases. It is important to classify AML correctly because of the special therapeutic and prognostic features of AML M3, which differently from other AML forms, has been successfully treated with cellular differentiating agents.
