Osteoblasts are a key component of the endosteal hematopoietic stem cell niche and are recognized with strong hematopoietic supporting activity. Similarly, mesenchymal stromal cells (MSC)‐derived osteoblast (M‐OST) conditioned media (OCM) enhance the growth of hematopoietic progenitors in culture and modulate their engraftment activity. This article aims to characterize the hematopoietic supporting activity of OCM by comparing the secretome of M‐OST to that of their precursor. Over 300 proteins are quantified by mass spectroscopy in media conditioned with MSC or M‐OST, with 47 being differentially expressed. Growth factors, extracellular matrix proteins, and proteins from the complement pathways are included. The functional contribution of selected proteins on the growth and differentiation of cord blood (CB) progenitors is tested. Secreted protein acidic and rich in cysteine and Galectin 3 (Gal3) have little impact on the growth of CB cells in serum‐free medium (SFM). In contrast, inhibition of the complement 3A receptor (C3a‐R) present on CB progenitors significantly reduces the growth of CD34⁺ cells in OCM cultures but not in SFM. These results provide new insights into changes in factors released by MSC undergoing osteoblast differentiation, and on paracrine factors that are partially responsible for the hematopoietic supporting activity of osteoblasts.

中文翻译：

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通过分泌组学深入了解成骨细胞的造血调节活动。


成骨细胞是骨内造血干细胞生态位的关键组成部分，具有很强的造血支持活性。同样，间充质基质细胞（MSC）衍生的成骨细胞（M-OST）条件培养基（OCM）可增强培养物中造血祖细胞的生长并调节其植入活性。本文旨在通过比较 M-OST 与其前体的分泌组来表征 OCM 的造血支持活性。通过质谱法对 MSC 或 M-OST 条件培养基中的 300 多种蛋白质进行定量，其中 47 种蛋白质存在差异表达。包括生长因子、细胞外基质蛋白和来自补体途径的蛋白质。测试了所选蛋白质对脐带血 (CB) 祖细胞生长和分化的功能贡献。富含半胱氨酸和半乳糖凝集素3（Gal3）的酸性分泌蛋白对CB细胞在无血清培养基（SFM）中的生长影响不大。相反，抑制 CB 祖细胞上存在的补体 3A 受体 (C3a-R) 显着降低 OCM 培养物中 CD34 ⁺细胞的生长，但在 SFM 中则不然。这些结果为MSC在成骨细胞分化过程中释放的因子的变化以及部分负责成骨细胞造血支持活性的旁分泌因子的变化提供了新的见解。