Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability.
Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability.
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DOI：
10.3389/fmolb.2022.767536
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
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间充质干细胞(MSCs)是治疗多种疾病最有前途的细胞来源之一。然而，由于MSCs的异质性，临床试验中的治疗效果一直不一致，这可能部分归因于它们的发育来源不明。侧中胚层也是脊椎动物胚胎中构成附件骨骼元素的间充质干细胞的发育来源。然而，由于缺乏对其特性的了解，从骨组织或骨髓中分离出均一的外侧中胚层来源的MSCs是困难的。在此，我们成功地建立了一种在特定条件下从人多能干细胞(HPSCs)分化为具有LM来源的MSCs的有效方法。LM-MSCs在细胞表面标志物、整体基因表达谱和免疫调节活性方面与骨髓间充质干细胞(BMSCs)相似，并表现出长骨中典型的同源域转录因子(Hox)基因表达模式。此外，我们还证明了与BMSCs相比，LM-MSCs具有更强的成骨/成软骨分化能力和造血支持能力。这些均一的LM-MSCs可以作为一种强大的工具来阐明它们在骨形成和造血中的确切作用，并可能成为治疗应用的潜在理想细胞来源。
Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.
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影响因子：
7.7
作者：
Isern J;García-García A;Martín AM;Arranz L;Martín-Pérez D;Torroja C;Sánchez-Cabo F;Méndez-Ferrer S
通讯作者：
Méndez-Ferrer S
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
7.7
作者：
Kim, Hyung-Seok;Neugebauer, Judith;Christian, Jan L.
通讯作者：
Christian, Jan L.
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
2.7
作者：
James, RG;Schultheiss, TM
通讯作者：
Schultheiss, TM