Dipartimento Scienze Cliniche e Molecolari, Università Politecnica delle Marche-Azienda Ospedali Riuniti, Ancona, Italy.
Stem Cells. 2012 May;30(5):965-74. doi: 10.1002/stem.1067.
Mature adipocytes are generally considered terminally differentiated because they have lost their proliferative abilities. Here, we studied the gene expression and functional properties of mature adipocytes isolated from human omental and subcutaneous fat tissues. We also focused on dedifferentiated adipocytes in culture and their morphologies and functional changes with respect to mature adipocytes, stromal-vascular fraction (SVF)-derived mesenchymal stem cells (MSCs) and bone marrow (BM)-derived MSCs. Isolated mature adipocytes expressed stem cell and reprogramming genes. They replicated in culture after assuming a fibroblast-like shape and expanded similarly to SVF- and BM-derived MSCs. During the dedifferentiation process, mature adipocytes lost their lineage gene expression profile, assumed the typical mesenchymal morphology and immunophenotype, expressed stem cell genes and differentiated into multilineage cells. Moreover, during the dedifferentiation process, we showed changes in the epigenetic status of mature adipocytes, which led dedifferentiated adipocytes to display a similar DNA methylation condition to BM-derived MSCs. Like SVF- and BM-derived MSCs, dedifferentiated adipocytes were able to inhibit the proliferation of stimulated lymphocytes in coculture while mature adipocytes stimulated their growth. Furthermore, dedifferentiated adipocytes maintained the survival and complete differentiation characteristic of hematopoietic stem cells. This is the first study that in addition to characterizing isolated and dedifferentiated adipocytes also reports on the immunoregulatory and hematopoietic supporting functions of these cells. This structural and functional characterization might have clinical applications of both mature and dedifferentiated adipocytes in such fields, as regenerative medicine.
成熟脂肪细胞通常被认为是终末分化的，因为它们已经失去了增殖能力。在这里，我们研究了从人网膜和皮下脂肪组织中分离出的成熟脂肪细胞的基因表达和功能特性。我们还专注于培养中的去分化脂肪细胞及其形态以及相对于成熟脂肪细胞、基质血管部分 (SVF) 衍生的间充质干细胞 (MSC) 和骨髓 (BM) 衍生的 MSC 的功能变化。分离的成熟脂肪细胞表达干细胞和重编程基因。它们在培养中复制，呈成纤维细胞样形状，并与 SVF 和 BM 衍生的 MSC 相似地扩增。在去分化过程中，成熟脂肪细胞失去了谱系基因表达谱，呈现出典型的间充质形态和免疫表型，表达干细胞基因并分化为多谱系细胞。此外，在去分化过程中，我们显示了成熟脂肪细胞表观遗传状态的变化，导致去分化的脂肪细胞表现出与 BM 衍生的 MSC 相似的 DNA 甲基化状态。与 SVF 和 BM 衍生的 MSC 一样，去分化的脂肪细胞能够在共培养中抑制受刺激的淋巴细胞增殖，而成熟的脂肪细胞则刺激其生长。此外，去分化的脂肪细胞保持了造血干细胞的存活和完全分化特征。这是第一项研究，除了描述分离和去分化的脂肪细胞外，还报告了这些细胞的免疫调节和造血支持功能。这种结构和功能特征可能在再生医学等领域中对成熟和去分化的脂肪细胞都具有临床应用价值。
