Laboratory of Clinical Cell Therapy, Université Libre de Bruxelles (ULB), Institut Jules Bordet, Brussels, Belgium.
PLoS One. 2013;8(3):e59756. doi: 10.1371/journal.pone.0059756. Epub 2013 Mar 21.
In multiple myeloma, bone marrow mesenchymal stromal cells support myeloma cell growth. Previous studies have suggested that direct and indirect interactions between malignant cells and bone marrow mesenchymal stromal cells result in constitutive abnormalities in the bone marrow mesenchymal stromal cells.
The aims of this study were to investigate the constitutive abnormalities in myeloma bone marrow mesenchymal stromal cells and to evaluate the impact of new treatments.
We demonstrated that myeloma bone marrow mesenchymal stromal cells have an increased expression of senescence-associated β-galactosidase, increased cell size, reduced proliferation capacity and characteristic expression of senescence-associated secretory profile members. We also observed a reduction in osteoblastogenic capacity and immunomodulatory activity and an increase in hematopoietic support capacity. Finally, we determined that current treatments were able to partially reduce some abnormalities in secreted factors, proliferation and osteoblastogenesis.
We showed that myeloma bone marrow mesenchymal stromal cells have an early senescent profile with profound alterations in their characteristics. This senescent state most likely participates in disease progression and relapse by altering the tumor microenvironment.
在多发性骨髓瘤中，骨髓间充质基质细胞支持骨髓瘤细胞生长。先前的研究表明，恶性细胞与骨髓间充质基质细胞之间的直接和间接相互作用导致骨髓间充质基质细胞的固有异常。
本研究旨在探讨骨髓瘤骨髓间充质基质细胞的固有异常，并评估新的治疗方法的影响。
我们证明骨髓瘤骨髓间充质基质细胞表达衰老相关β-半乳糖苷酶增加，细胞体积增大，增殖能力降低，表现出特征性的衰老相关分泌表型成员。我们还观察到成骨能力和免疫调节活性降低，造血支持能力增加。最后，我们确定目前的治疗方法能够部分减少分泌因子、增殖和成骨方面的一些异常。
我们表明骨髓瘤骨髓间充质基质细胞具有早期衰老表型，其特征发生了深刻改变。这种衰老状态很可能通过改变肿瘤微环境参与疾病的进展和复发。
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