RESUMO
The fate of human hematopoietic stem cells (HSCs)/progenitor cells (HPCs) is influenced by bone marrow (BM) stromal cells. To investigate the role of stromal cells in the hematopoietic support, we have transduced human fetal BM stromal cells (FBMSCs) with a human telomerase catalytic subunit (hTERT). One of the resultant cell lines was identified as osteoblasts, because it contained mineral deposits and constitutively expressed osteogenic genes osteocalcin, osteopontin, collagen type I, osteoblast marker alkaline phosphatase, but not marrow stromal cell marker STRO-1 and CD105. The hTERT-transduced fetal BM-derived osteoblastic cells (FBMOB-hTERT) can actively maintain the capacity of self-renewal and multipotency of HSCs/HPCs at least partly through transcriptional up-regulation of hematopoietic growth factors such as stem cell growth factors (SCFs) and Wnt-5A during interaction with HSCs/HPCs. The enhanced transcription of SCFs and Wnt-5A appears to be mediated by CD29 signaling. Moreover, the FBMOB-hTERT cells seem superior to primary FBMSCs in supporting hematopoiesis, because they are more potent than primary FBMSCs in supporting the ex vivo expansion and long-term culture initiating cells activity of HSCs. The FBMOB-hTERT cell line has been maintained in vitro more than 125 population doublings without tumorigenicity. The results indicate that the FBMOB-hTERT is useful for the study of molecular mechanisms by which osteoblasts support hematopoiesis.
Assuntos
Células da Medula Óssea/citologia , Linhagem Celular/citologia , Hematopoese , Osteoblastos/citologia , Telomerase/genética , Animais , Células da Medula Óssea/enzimologia , Domínio Catalítico , Linhagem Celular/enzimologia , Feto/citologia , Hematopoese/genética , Fatores de Crescimento de Células Hematopoéticas/genética , Fatores de Crescimento de Células Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/enzimologia , Humanos , Camundongos , Osteoblastos/enzimologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Células Estromais/citologia , Células Estromais/enzimologia , Transdução Genética , Regulação para Cima , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteína Wnt-5a , Quinases da Família srcRESUMO
Stromal cell derived factor (SDF), expressing on bone marrow stromal cells is a CXC-type chemokine, which specifically chemoattracts hematopoietic stem cells (HSCs) expressing CXCR4. SDF plays important roles in homing and mobilizing of HSCs. In this paper the regulatory mechanism of SDF/CXCR4 in the HSC migration process is mainly reviewed.