Stem Cell and Cancer Biology Group, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, India.
Department of Hematology, Gauhati Medical College and Hospital, Guwahati, India.
J Biomed Sci. 2018 Jan 19;25(1):5. doi: 10.1186/s12929-018-0407-7.
Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles.
We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine. We also tested anti-cancer effects of drug treated MSC on leukemia cells.
Treatment with the chemotherapeutic drugs resulted in functional defects in MSC, leading to reduced proliferation, osteogenic and adipogenic differentiation. The drug treated MSC also showed decreased expression of cell surface receptors, and the changes in proliferation, phenotype and differentiation defect was partially reversible after withdrawing the drugs from the cells. The drug treated MSC showed increased expression of cytokines, IL6, FGF2 and TNFA but reduced levels of differentiation markers SOX9 and ACTC1. Drug treated MSC also contributed to reduced anti-cancer effects in leukemia cells.
Chemotherapeutic drug treatment altered the phenotype, osteogenic and adipogenic differentiation potential of MSC and modified the gene expression profile of the cells to render them more chemoprotective of the leukemic cells. Thus, additional therapeutic efforts to target the stromal cell population will help in preventing chemoresistance, disease relapse in leukemia and to maintain a healthy bone marrow stroma.
间充质干细胞（MSC）被用于多种治疗应用，以改善骨骼、心脏、神经组织的功能，并促进造血干细胞的再定居。MSC 产生骨髓中非造血基质细胞，对于维持正常造血至关重要。用于治疗白血病的化疗药物会广泛损伤基质细胞，并改变其基因表达谱。
我们在化疗药物阿糖胞苷、柔红霉素和长春新碱处理的 MSC 中，确定了脂肪生成、成骨分化、表型和基因表达的变化。我们还测试了经药物处理的 MSC 对白血病细胞的抗癌作用。
化疗药物处理导致 MSC 功能缺陷，导致增殖、成骨和成脂分化减少。药物处理的 MSC 还表现出细胞表面受体表达减少，并且在从细胞中去除药物后，增殖、表型和分化缺陷的变化部分可逆。药物处理的 MSC 还表现出细胞因子、IL6、FGF2 和 TNFA 的表达增加，但分化标志物 SOX9 和 ACTC1 的水平降低。药物处理的 MSC 还导致白血病细胞的抗癌作用降低。
化疗药物处理改变了 MSC 的表型、成骨和成脂分化潜能，并修饰了细胞的基因表达谱，使其对白血病细胞更具化学保护作用。因此，针对基质细胞群体的额外治疗努力将有助于预防化疗耐药、白血病复发，并维持健康的骨髓基质。
