The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases
The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases
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DOI：
10.3390/cells9020431
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发表时间：
2020-02-01
期刊：
影响因子：
6
通讯作者：
Kuci, Selim
中科院分区：
文献类型：
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作者：
Kuci, Zyrafete;Jordan, Christiane;Kuci, Selim
由于对非恶性血液病（NMHD）患者间充质基质细胞（MSC）的生物学知之甚少，在本研究中，我们对NMHD-MSC的表型和功能活性进行了基本表征。重型地中海贫血（TM）患者的骨髓（BM）中有核细胞（BM-MNCs）/mL BM的数量显著高于健康供体（P < 0.0001），但这并不导致每毫升BM中集落形成单位-成纤维细胞（CFU-F）的数量增加。与此相反，镰状细胞病（SCD）患者的1 × 10（6）BM-MNCs产生的CFU-Fs显著高于TM-BM-MNCs（P < 0.013）和对照组（P < 0.02）。此外，NMHD-MSCs表达显著较低水平的CD 146分子，表现出与健康供体的MSCs相同的增殖潜力，并沿着三个谱系（成骨细胞、软骨细胞和脂肪细胞）分化，除了TM-MSCs在脂肪细胞中分化较弱。与其他NMHD-MSC和健康供体的MSC相比，TM-MSC表现出受损的体外免疫抑制潜力。值得注意的是，NMHD-MSC的大部分免疫抑制作用是通过前列腺素E2（PGE 2）介导的，因为吲哚美辛（PGE 2合成的抑制剂）能够显著逆转这种作用。因此，我们的研究结果表明，NMHD-MSCs，除了TM-MSCs，可用作移植后并发症，如移植失败，移植物抗宿主病（GvHD）和骨坏死的自体细胞为基础的治疗。
As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 x 10(6) BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors' MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors' MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.