Improved osteogenesis and upregulated immunogenicity in human placenta-derived mesenchymal stem cells primed with osteogenic induction medium.
Improved osteogenesis and upregulated immunogenicity in human placenta-derived mesenchymal stem cells primed with osteogenic induction medium.
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用成骨诱导培养基引发的人胎盘源性间充质干细胞改善成骨作用并上调免疫原性
DOI：
10.1186/s13287-016-0400-6
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发表时间：
2016-09-20
影响因子：
7.5
通讯作者：
Shi Q
中科院分区：
文献类型：
--
作者：
Fu X;Yang H;Zhang H;Wang G;Liu K;Gu Q;Tao Y;Chen G;Jiang X;Li G;Gu Y;Shi Q
背景间充质干细胞（Mesenchymal Stem Cells，MSCs）因其具有多向分化潜能和低免疫原性而被广泛应用于细胞治疗。然而，同种异体间充质干细胞在体内的低分化效率和不可预测的免疫原性限制了其在治疗性治疗中的成功。在此，我们评估了人胎盘来源的骨髓间充质干细胞的分化潜力和免疫原性与成骨启动和去分化process.MethodsMSCs从人胎盘进行成骨诱导，然后培养在无成骨因子的培养基中，所获得的细胞群体被称为去分化间充质干细胞（De-MSCs）。体外诱导脱骨髓间充质干细胞向成骨、软骨和脂肪细胞分化。通过Cell-Counting Kit-8或氚化胸苷（[3 H]-TdR）掺入定量细胞增殖。同时采用实时荧光定量PCR和组织学染色检测脱细胞间充质干细胞体内成骨能力。结果De-MSCs具有与MSCs相似的多向分化潜能和低免疫原性。在体外和体内再成骨诱导后，脱骨髓间充质干细胞表现出比骨髓间充质干细胞更高的分化能力。值得注意的是，De-MSC具有与其成骨相关的上调免疫原性，这反映在表面上共刺激分子的交替表达和对T细胞活化的抑制降低。在功能上，去MSC衍生的成骨细胞可以引发BALB/c小鼠外周血和脾脏中的淋巴细胞in vivo.ConclusionsThese数据是具有重要意义的潜在应用的去MSC作为再生医学和组织工程的替代资源。为了避免在同种异体De-MSC治疗过程中被宿主排斥，我们建议应考虑免疫干预，以促进免疫接受和整合，因为在临床应用中，再分化的De-MSC的免疫原性上调。
BackgroundMesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage potential and low immunogenicity. However, low differentiation efficiency and unpredictable immunogenicity of allogeneic MSCs in vivo limit their success in therapeutic treatment. Herein, we evaluated the differentiation potential and immunogenicity of human placenta-derived MSCs manipulated with osteogenic priming and dedifferentiation process.MethodsMSCs from human placentas were subjected to osteogenic induction and then cultivated in osteogenic factor-free media; the obtained cell population was termed dedifferentiated mesenchymal stem cells (De-MSCs). De-MSCs were induced into osteo-, chondro- and adipo-differentiation in vitro. Cell proliferation was quantified by a Cell-Counting Kit-8 or tritiated thymidine ([3H]-TdR) incorporation. Meanwhile, the osteogenesis of De-MSCs in vivo was assayed by real-time PCR and histological staining. The expressions of stem cell markers and co-stimulatory molecules on De-MSCs and lymphocytes from primed BALB/c mouse with De-MSCs were determined by flow cytometry.ResultsDe-MSCs exhibited some properties similar to MSCs including multiple differentiation potential and hypoimmunogenicity. Upon re-osteogenic induction, De-MSCs exhibited higher differentiation capability than MSCs both in vitro and in vivo. Of note, De-MSCs had upregulated immunogenicity in association with their osteogenesis, reflected by the alternated expressions of co-stimulatory molecules on the surface and decreased suppression on T cell activation. Functionally, De-MSC-derived osteoblasts could prime lymphocytes of peripheral blood and spleen in BALB/c mice in vivo.ConclusionsThese data are of great significance for the potential application of De-MSCs as an alternative resource for regenerative medicine and tissue engineering. In order to avoid being rejected by the host during allogeneic De-MSC therapy, we suggest that immune intervention should be considered to boost the immune acceptance and integration because of the upregulated immunogenicity of De-MSCs with redifferentiation in clinical applications.
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通过成骨诱导培养基引发获得的表观遗传记忆可改善间充质干细胞的成骨和其他特性
影响因子：
4.6
作者：
Rui Y;Xu L;Chen R;Zhang T;Lin S;Hou Y;Liu Y;Meng F;Liu Z;Ni M;Tsang KS;Yang F;Wang C;Chan HC;Jiang X;Li G
通讯作者：
Li G
影响因子：
12.4
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具有改善治疗潜力的去分化重编程间充质干细胞
影响因子：
5.2
作者：
Liu, Yang;Jiang, Xiaohua;Chan, Hsiao Chang
通讯作者：
Chan, Hsiao Chang
影响因子：
5.1
作者：
Chuang, C-K;Sung, L-Y;Hu, Y-C
通讯作者：
Hu, Y-C
影响因子：
14.9
作者：
Ehlers C;Schirmer S;Kehlenbach RH;Hauber J;Chemnitz J
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Chemnitz J