Department of Clinical Cell Biology, Institute of Regional Health Science, University of Southern Denmark, Lillebaelt Hospital, Vejle, Denmark.
Department of Pathology, Clinical Cell Biology, Odense University Hospital, Odense, Denmark.
PLoS One. 2021 Apr 20;16(4):e0250081. doi: 10.1371/journal.pone.0250081. eCollection 2021.
Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- "hematopoietic stem cells and multipotent progenitors" and a population of CD34+/CD38+ "progenitors" based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other "hematopoietic stem cells and multipotent progenitors" and other "progenitors") within 30 μm of "hematopoietic stem cells and multipotent progenitors", "progenitors", and "random cell profiles". We show that the microenvironment of the "hematopoietic stem cells and multipotent progenitors" is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the "progenitors" is significantly enriched in capillaries, other "progenitors", bone surfaces and arteries.
造血干细胞的休眠和祖细胞的形成是由来自骨髓微环境的信号所指导的。人们对小鼠造血干细胞微环境有了相当多的了解，而对小鼠祖细胞微环境的了解则较少，对人类这些微环境的了解就更少了。对这些微环境的特征进行描述对于理解造血作用以及在临床上寻找针对骨髓恶性肿瘤的新治疗方法是决定性的。然而，这同样具有挑战性，因为造血干细胞在复杂的骨髓环境中很难被检测到。在本研究中，我们正在对人类造血干细胞和祖细胞微环境进行特征描述。我们从十个健康志愿者中获得了三个相邻的骨髓切片。其中一个用于根据免疫荧光模式/强度和细胞形态，识别 CD34+/CD38-“造血干细胞和多能祖细胞”和 CD34+/CD38+“祖细胞”群体。另外两个分别用于 CD34/CD56 和 CD34/SMA 的免疫染色。利用综合信息，我们对距离“造血干细胞和多能祖细胞”、“祖细胞”和“随机细胞图谱”30μm 内的 9 种骨髓成分（脂肪细胞、巨核细胞、骨表面、4 种不同的血管类型（动脉、毛细血管、窦状血管和收集窦）、其他“造血干细胞和多能祖细胞”和其他“祖细胞”）进行了非计算机辅助的定量。我们表明，“造血干细胞和多能祖细胞”的微环境富含窦状血管和巨核细胞，而“祖细胞”的微环境富含毛细血管、其他“祖细胞”、骨表面和动脉。
