Grymula Katarzyna, Tarnowski Maciej, Piotrowska Katarzyna, Suszynska Malwina, Mierzejewska Katarzyna, Borkowska Sylwia, Fiedorowicz Katarzyna, Kucia Magda, Ratajczak Mariusz Z
Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
J Cell Mol Med. 2014 Sep;18(9):1797-806. doi: 10.1111/jcmm.12315. Epub 2014 Jun 4.
The concept that bone marrow (BM)-derived cells may participate in neural regeneration remains controversial, and the identity of the specific cell type(s) involved remains unknown. We recently reported that the adult murine BM contains a highly mobile population of Sca-1(+) Lin(-) CD45(-) cells known as very small embryonic/epiblast-like stem cells (VSELs) that express several markers of pluripotency such as Oct-4. In the BM microenvironment, these cells are kept quiescent because of epigenetic modification of certain paternally imprinted genes. However, as reported, these cells can be mobilized in mice in an experimental model of stroke and express several genes involved in neurogenesis while circulating in peripheral blood (PB). In the current work, we employed a model of toxic brain damage, which is induced by administration of kainic acid, to see not only whether VSELs can be mobilized into PB in response to this neurotoxin, but, more importantly, whether they proliferate and expand in BM tissue. We report here for the first time that brain damage leads to activation and expansion of the BM pool of quiescent VSELs, which precedes their subsequent egress into PB. Harnessing these cells in neural tissue regeneration is currently one of the challenges in regenerative medicine.
骨髓（BM）来源的细胞可能参与神经再生这一概念仍存在争议，且所涉及的特定细胞类型的身份尚不清楚。我们最近报道，成年小鼠骨髓中含有一群高度可移动的Sca-1(+) Lin(-) CD45(-)细胞，称为非常小的胚胎/上胚层样干细胞（VSELs），它们表达几种多能性标记物，如Oct-4。在骨髓微环境中，由于某些父系印记基因的表观遗传修饰，这些细胞处于静止状态。然而，如报道所示，在中风实验模型中，这些细胞可在小鼠体内被动员，并在外周血（PB）中循环时表达几种参与神经发生的基因。在当前的工作中，我们采用了一种由给予 kainic 酸诱导的毒性脑损伤模型，不仅要观察VSELs是否能响应这种神经毒素而被动员到外周血中，更重要的是，它们是否在骨髓组织中增殖和扩增。我们首次在此报告，脑损伤导致静止的VSELs骨髓池的激活和扩增，这在它们随后进入外周血之前发生。在神经组织再生中利用这些细胞目前是再生医学面临的挑战之一。
