Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
PLoS One. 2012;7(2):e31741. doi: 10.1371/journal.pone.0031741. Epub 2012 Feb 23.
The hematopoietic inductive microenvironment (HIM) is where hematopoietic stem/progenitor cells grow and develop. Hematopoietic stromal cells were the key components of the HIM. In our previous study, we had successfully cultured and isolated human cord blood-derived stromal cells (HUCBSCs) and demonstrated that they could secret hemopoietic growth factors such as GM-CSF, TPO, and SCF. However, it is still controversial whether HUCBSCs can be used for reconstruction of HIM. In this study, we first established a co-culture system of HUCBSCs and cord blood CD34(+) cells and then determined that using HUCBSCs as the adherent layer had significantly more newly formed colonies of each hematopoietic lineage than the control group, indicating that HUCBSCs had the ability to promote the proliferation of hematopoietic stem cells/progenitor cells. Furthermore, the number of colonies was significantly higher in vascular cell adhesion molecule-1 (VCAM-1)-modified HUCBSCs, suggesting that the ability of HUCBSCs in promoting the proliferation of hematopoietic stem cells/progenitor cells was further enhanced after having been modified with VCAM-1. Next, HUCBSCs were infused into a radiation-damaged animal model, in which the recovery of hematopoiesis was observed. The results demonstrate that the transplanted HUCBSCs were "homed in" to bone marrow and played roles in promoting the recovery of irradiation-induced hematopoietic damage and repairing HIM. Compared with the control group, the HUCBSC group had significantly superior effectiveness in terms of the recovery time for hemogram and myelogram, CFU-F, CFU-GM, BFU-E, and CFU-Meg. Such differences were even more significant in VCAM-1-modified HUCBSCs group. We suggest that HUCBSCs are able to restore the functions of HIM and promote the recovery of radiation-induced hematopoietic damage. VCAM-1 plays an important role in supporting the repair of HIM damage.
造血诱导微环境（HIM）是造血干细胞/祖细胞生长和发育的地方。造血基质细胞是 HIM 的关键组成部分。在我们之前的研究中，我们已经成功地培养和分离了人脐血来源的基质细胞（HUCBSCs），并证明它们可以分泌造血生长因子，如 GM-CSF、TPO 和 SCF。然而，HUCBSCs 是否可用于 HIM 的重建仍然存在争议。在这项研究中，我们首先建立了 HUCBSCs 和脐血 CD34(+)细胞的共培养系统，然后确定使用 HUCBSCs 作为贴壁层比对照组有更多的每个造血谱系的新形成的集落，表明 HUCBSCs 具有促进造血干细胞/祖细胞增殖的能力。此外，VCAM-1 修饰的 HUCBSCs 的集落数量明显更高，表明 VCAM-1 修饰后，HUCBSCs 促进造血干细胞/祖细胞增殖的能力进一步增强。接下来，将 HUCBSCs 注入辐射损伤的动物模型中，观察造血的恢复情况。结果表明，移植的 HUCBSCs 归巢到骨髓中，并在促进辐射诱导的造血损伤恢复和修复 HIM 中发挥作用。与对照组相比，HUCBSC 组在血象和骨髓象、CFU-F、CFU-GM、BFU-E 和 CFU-Meg 的恢复时间方面具有明显的优势。在 VCAM-1 修饰的 HUCBSCs 组中差异更加显著。我们认为 HUCBSCs 能够恢复 HIM 的功能并促进辐射诱导的造血损伤的恢复。VCAM-1 在支持 HIM 损伤修复中起重要作用。
