Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran.
Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
Stem Cell Res Ther. 2023 Jul 4;14(1):173. doi: 10.1186/s13287-023-03400-w.
Polyploid cells can be found in a wide evolutionary spectrum of organisms. These cells are assumed to be involved in tissue regeneration and resistance to stressors. Although the appearance of large multinucleated cells (LMCs) in long-term culture of bone marrow (BM) mesenchymal cells has been reported, the presence and characteristics of such cells in native BM and their putative role in BM reconstitution following injury have not been fully investigated.
BM-derived LMCs were explored by time-lapse microscopy from the first hours post-isolation to assess their colony formation and plasticity. In addition, sub-lethally irradiated mice were killed every other day for four weeks to investigate the histopathological processes during BM regeneration. Moreover, LMCs from GFP transgenic mice were transplanted to BM-ablated recipients to evaluate their contribution to tissue reconstruction.
BM-isolated LMCs produced mononucleated cells with characteristics of mesenchymal stromal cells. Time-series inspections of BM sections following irradiation revealed that LMCs are highly resistant to injury and originate mononucleated cells which reconstitute the tissue. The regeneration process was synchronized with a transient augmentation of adipocytes suggesting their contribution to tissue repair. Additionally, LMCs were found to be adiponectin positive linking the observations on multinucleation and adipogenesis to BM regeneration. Notably, transplantation of LMCs to myeloablated recipients could reconstitute both the hematopoietic system and BM stroma.
A population of resistant multinucleated cells reside in the BM that serves as the common origin of stromal and hematopoietic lineages with a key role in tissue regeneration. Furthermore, this study underscores the contribution of adipocytes in BM reconstruction.
多倍体细胞存在于广泛的生物进化谱系中。这些细胞被认为参与组织再生和抵抗应激源。虽然骨髓（BM）间充质细胞长期培养中出现大多核细胞（LMC）的现象已有报道，但在天然 BM 中这些细胞的存在和特征及其在损伤后 BM 重建中的潜在作用尚未得到充分研究。
通过延时显微镜从分离后的最初几个小时开始探索 BM 来源的 LMC，以评估其集落形成和可塑性。此外，每隔一天处死亚致死剂量照射的小鼠，以研究 BM 再生过程中的组织病理学过程。此外，将 GFP 转基因小鼠的 LMC 移植到 BM 消融受者中，以评估其对组织重建的贡献。
BM 分离的 LMC 产生具有间充质基质细胞特征的单核细胞。照射后 BM 切片的时间序列检查表明，LMC 对损伤具有高度抗性，并且起源于单核细胞，这些单核细胞重建组织。再生过程与脂肪细胞的短暂增加同步，提示其对组织修复的贡献。此外，发现 LMC 是脂联素阳性的，将多核化和脂肪生成的观察结果与 BM 再生联系起来。值得注意的是，将 LMC 移植到骨髓消融受者中可以重建造血系统和 BM 基质。
在 BM 中存在一种具有抗性的多核细胞群体，它是基质和造血谱系的共同起源，在组织再生中起着关键作用。此外，本研究强调了脂肪细胞在 BM 重建中的作用。
