Characterization of Mesenchymal Progenitor Cell Populations Directly Derived from Human Dermis

Characterization of Mesenchymal Progenitor Cell Populations Directly Derived from Human Dermis
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DOI:
10.1089/scd.2013.0207
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发表时间:
2014-03-15
影响因子:
4
通讯作者:
Dunbar, P. Rod
Dunbar, P. Rod
中科院分区:
医学3区
文献类型:
--
作者:
Feisst, Vaughan;Brooks, Anna E. S.;Dunbar, P. Rod

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人真皮中的间充质干细胞(MSC)和祖细胞(MPC)群体的特征仍然很差,尽管它们对伤口修复和许多皮肤疾病的发病机制很重要。为了鉴定人真皮中的MSC/MPC群体,我们开发了一种11标记流式细胞术技术,该技术能够分选间充质细胞群体用于功能测定,使用来自人脂肪组织的脂肪源性干细胞(ASC)作为阳性对照。两个真皮细胞群体具有与ASC相似的表型:均为CD 34(+)CD 73(+)CD 105(-)/低,并且缺乏c-kit(CD 117)和造血或血管标记物(CD 31、CD 45、CD 146和HLA-DR)的表达。然而,尽管ASC是CD 36(+/-)CD 90(+),但真皮间充质祖细胞(DMPC)分为占主导地位的CD 36(-)CD 90(+)群体(DMPC 1)和小的CD 36(+)CD 90(-)群体(DMPC 2)。这两个群体都能够分化成脂肪细胞,但只有DMPC 1定位于血管周围的位置,类似于ASCs的报告。流式细胞术数据的重新设门显示DMPC 1和DMPC 2均为CD 45(-)CD 73(+)CD 146(-)群体的一部分,具有可变的CD 34表达。这表明,CD 34可能不是人真皮中DMPC群体的稳定标志物,这与人骨髓中MSC的数据一致,并且与我们在细胞培养物上从ASC和DMPC中观察到的CD 34的损失一致。这些数据使未来的研究DMPCs在健康和疾病,也可以解释为什么一些间充质细胞系来源于人真皮表现出MSC的特性。
Mesenchymal stem cell (MSC) and progenitor cell (MPC) populations in human dermis remain poorly characterized, despite their importance to wound repair and the pathogenesis of many skin diseases. To identify MSC/MPC populations in human dermis we developed an 11-marker flow cytometry technique that enabled sorting of mesenchymal cell populations for functional assays, using adipose-derived stem cells (ASCs) from human adipose tissue as a positive control. Two populations of dermal cells had similar phenotypes to ASCs: both were CD34(+) CD73(+) CD105(-)/low, and lacked expression of c-kit (CD117) and hematopoietic or vascular markers (CD31, CD45, CD146, and HLA-DR). However, whereas ASCs were CD36(+/-) CD90(+), dermal mesenchymal progenitor cells (DMPCs) were split between a dominant CD36(-) CD90(+) population (DMPC1) and a small CD36(+) CD90(-) population (DMPC2). Both these populations were capable of differentiating into adipocytes, but only DMPC1 localized to a perivascular location, similar to that reported for ASCs. Re-gating of the flow cytometry data revealed that both DMPC1 and DMPC2 were part of CD45(-) CD73(+) CD146(-) populations with variable expression of CD34. This suggests that CD34 may not be a stable marker of DMPC populations in human dermis, consistent with data from MSCs in human bone marrow, and with the loss of CD34 we observed from both ASCs and DMPCs on cell culture. These data enable future study of DMPCs in health and disease, and may also explain why some mesenchymal cell lines derived from human dermis exhibit characteristics of MSCs.