Kucia Magda, Wojakowski Wojtek, Reca Ryan, Machalinski Bogdan, Gozdzik Jolanta, Majka Marcin, Baran Jarek, Ratajczak Janina, Ratajczak Mariusz Z
Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, 529 South Jackson Street, Louisville, KY 40202, USA.
Arch Immunol Ther Exp (Warsz). 2006 Mar-Apr;54(2):121-35. doi: 10.1007/s00005-006-0015-1. Epub 2006 Mar 28.
Recently we identified in bone marrow (BM) by employing chemotactic isolation to SDF-1 gradient combined with real time RT-PCR analysis a mobile population of CXCR4+ BM mononuclear cells that express mRNA for various markers of early tissue-committed stem cells (TCSCs). In this study we evaluated whether TCSCs respond to other motomorphogens, such as hepatocyte growth factor (HGF) and leukemia inhibitory factor (LIF).
We again employed chemotactic isolation combined with real-time RT-PCR analysis to assess whether murine and human BM contain TCSCs that respond to HGF and LIF gradients. We also evaluated expressions of HGF and LIF in damaged organs.
We noted that the number of TCSCs is highest in BM from young (1- to 2-month-old) mice and decreases in 1-year-old animals. Murine and human TCSCs 1) respond to HGF and LIF gradients in addition to an SDF-1 gradient, 2) reside in populations of BM-derived non-hematopoietic CD45-cells, and 3) are released (mobilized) from BM into the peripheral blood (PB) during tissue injury (e.g. after partial body irradiation).
These findings further support our theory of the BM as a "hideout" for TCSCs and we suggest that their presence in BM tissue should be considered before experimental evidence is interpreted simply as transdifferentiation/plasticity of hematopoietic stem cells. Since we demonstrated that not only SDF-1, but also HGF and LIF are upregulated in damaged tissues, we postulate that CXCR4+ c-Met+ LIF-R+ TCSC could be mobilized from the BM into the PB, from which they are subsequently chemoattracted to damaged organs, where they play a role in tissue repair/regeneration.
最近，我们通过利用趋化分离技术结合实时逆转录聚合酶链反应（RT-PCR）分析，在骨髓（BM）中鉴定出一群CXCR4+骨髓单个核细胞，它们可移动，并且表达多种早期组织定向干细胞（TCSCs）标志物的mRNA。在本研究中，我们评估了TCSCs是否对其他运动形态发生素作出反应，例如肝细胞生长因子（HGF）和白血病抑制因子（LIF）。
我们再次采用趋化分离技术结合实时RT-PCR分析，以评估小鼠和人类骨髓中是否含有对HGF和LIF梯度作出反应的TCSCs。我们还评估了受损器官中HGF和LIF的表达。
我们注意到，年轻（1至2个月大）小鼠骨髓中的TCSCs数量最高，而在1岁动物中数量减少。小鼠和人类TCSCs：1）除了对SDF-1梯度作出反应外，还对HGF和LIF梯度作出反应；2）存在于骨髓来源的非造血CD45-细胞群体中；3）在组织损伤期间（例如局部身体照射后）从骨髓释放（动员）到外周血（PB）中。
这些发现进一步支持了我们关于骨髓是TCSCs“藏身之处”的理论，并且我们建议，在将实验证据简单解释为造血干细胞的转分化/可塑性之前，应考虑它们在骨髓组织中的存在。由于我们证明不仅SDF-1，而且HGF和LIF在受损组织中上调，我们推测CXCR4+ c-Met+ LIF-R+ TCSC可从骨髓动员到PB中，随后它们被趋化吸引到受损器官，在那里它们在组织修复/再生中发挥作用。
