RESUMO
Using experimental mouse models, hematopoietic potential has been shown to exist within skeletal muscle. In humans, the clinical utility of using muscle-derived hematopoietic progenitors remains uncertain. Here, we evaluate the hematopoietic potential of human skeletal muscle. De novo adult muscle contained markedly reduced levels of hematopoietic colony-forming units (hCFU) and negligible responsiveness to hematopoietic ex vivo culture conditions that augment hematopoietic activity of fetal muscle. Neither fetal nor adult muscle yielded significant engraftment in transplanted immune-deficient mice. Although adult muscle possessed 1.5+/-0.9 hCFU/g, similar hematopoietic activity (2.3+/-0.17 hCFU) could also be demonstrated from as little as 3-10 microl of contaminating peripheral blood. We suggest that the clinical utility of adult skeletal muscle as an alternative source of hematopoietic cells in humans appears limited due to the low yield of blood-forming precursors and their lack of responsiveness to ex vivo expansion.
Assuntos
Hematopoese , Células-Tronco Hematopoéticas/citologia , Músculo Esquelético/citologia , Adulto , Animais , Técnicas de Cultura de Células , Proliferação de Células , Células Cultivadas , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Humanos , Camundongos , Camundongos SCID , Músculo Esquelético/fisiologia , Transplante HeterólogoRESUMO
We report here the molecular cloning of an approximately 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the 1-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lines in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain.
