Pituch-Noworolska Anna, Majka Marcin, Janowska-Wieczorek Anna, Baj-Krzyworzeka Monika, Urbanowicz Barbara, Malec Edward, Ratajczak Mariusz Z
Polish-American Children's Hospital, Medical College, Jagiellonian University, Cracow, Poland.
Folia Histochem Cytobiol. 2003;41(1):13-21.
The trans-differentiation hypothesis of adult tissue-specific stem cells has been recently questioned because of insufficient proof that the so-called plasticity experiments were performed on pure populations of tissue-specific stem cells. It was shown recently, for example, that the formation of haematopoietic colonies by muscle cells depended on the presence of haematopoietic stem/progenitor cells residing within the muscle tissue and hence was not related to the plasticity of the muscle stem cells. The explanation for the presence in, or homing into, muscles of haematopoietic stem cells is, however, not clear. In our study, we hypothesised that muscle tissues secrete stromal-derived factor (SDF)- 1, an alpha-chemokine for haematopoietic stem cells (HSC), which could attract HSC circulating in peripheral blood into muscle tissue. We found, using RT-PCR and immunocytochemistry, that SDF-1 was expressed in human heart and skeletal muscles. Moreover, muscle satellite cells, which are pivotal for regeneration of muscle, highly expressed on their surface CXCR4, a G-protein-coupled receptor that binds SDF-1. To determine whether the CXCR4 receptor is functional on muscle satellite/progenitor cells, we stimulated murine satellite cells (the C2C12 cell line) with SDF-1 and demonstrated the phosphorylation of p42/44 MAPK and AKT serine-threonine kinase in these cells. Moreover, we showed that SDF-1 gradient chemoattracts these cells. We postulate that the CXCR4-positive muscle satellite and CXCR4-positive HSC circulating in the peripheral blood compete for occupancy of SDF-1-positive stem cell niches that are present in bone marrow and muscle tissues. Thus, we suggest that competition for common niches by various circulating CXCR4-positive stem cells and their ability to home to the SDF-1-positive niches in various organs, is a better explanation than stem cell plasticity of why (i) haematopoietic colonies can be cultured from muscles and (ii) early muscle progenitors could be cultured from bone marrow.
成体组织特异性干细胞的转分化假说最近受到质疑，因为没有充分证据表明所谓的可塑性实验是在纯的组织特异性干细胞群体上进行的。例如，最近有研究表明，肌肉细胞形成造血集落依赖于肌肉组织中存在的造血干细胞/祖细胞，因此与肌肉干细胞的可塑性无关。然而，造血干细胞存在于肌肉中或归巢至肌肉的原因尚不清楚。在我们的研究中，我们推测肌肉组织分泌基质衍生因子（SDF）-1，这是一种针对造血干细胞（HSC）的α趋化因子，它可以吸引外周血中循环的HSC进入肌肉组织。我们通过逆转录聚合酶链反应（RT-PCR）和免疫细胞化学发现，SDF-1在人心脏和骨骼肌中表达。此外，对肌肉再生至关重要的肌肉卫星细胞在其表面高表达CXCR4，这是一种与SDF-1结合的G蛋白偶联受体。为了确定CXCR4受体在肌肉卫星/祖细胞上是否具有功能，我们用SDF-1刺激小鼠卫星细胞（C2C12细胞系），并证明这些细胞中p42/44丝裂原活化蛋白激酶（MAPK）和AKT丝氨酸-苏氨酸激酶发生磷酸化。此外，我们还表明SDF-1梯度对这些细胞具有化学趋化作用。我们推测，外周血中循环的CXCR4阳性肌肉卫星细胞和CXCR4阳性HSC竞争占据骨髓和肌肉组织中存在的SDF-1阳性干细胞龛。因此，我们认为，各种循环的CXCR4阳性干细胞对共同龛的竞争以及它们归巢至各器官中SDF-1阳性龛的能力，比干细胞可塑性更能解释为什么（i）可以从肌肉中培养出造血集落，以及（ii）可以从骨髓中培养出早期肌肉祖细胞。
