Bakhshi Tiki, Zabriskie Ryan C, Bodie Shamanique, Kidd Shannon, Ramin Susan, Paganessi Laura A, Gregory Stephanie A, Fung Henry C, Christopherson Kent W
Division of Maternal-Fetal Medicine, The University of Texas Medical School at Houston, Houston, Texas, USA.
Transfusion. 2008 Dec;48(12):2638-44. doi: 10.1111/j.1537-2995.2008.01926.x. Epub 2008 Sep 16.
Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated.
Umbilical cord-derived MSCs (UC-MSCs) were cultured from the Wharton's jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay.
Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays.
These data suggest the potential therapeutic application of Wharton's jelly-derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.
造血干细胞(HSCs)通常取自骨髓、动员外周血和脐带血。间充质干细胞(MSCs)传统上是从骨髓中分离出来的。骨髓来源的间充质干细胞(BM-MSCs)此前已证明其能够作为饲养层支持体外脐带血扩增。然而,使用BM-MSCs来支持脐带血的生长、分化和植入可能并非移植目的的理想选择。因此,评估了一种新来源——脐带华通氏胶中的间充质干细胞作为脐带血造血干细胞长期培养的基质支持的潜力。
从脐带段的华通氏胶中培养脐带来源的间充质干细胞(UC-MSCs)。然后对UC-MSCs进行12种细胞表面受体表达谱分析,并在长期培养起始细胞(LTC-IC)试验中测试其支持脐带血造血干细胞的能力。
培养后,UC-MSCs表达一组特定的细胞表面标志物(CD29、CD44、CD73、CD90、CD105、CD166和HLA-A),并缺乏其他标志物(CD45、CD34、CD38、CD117和HLA-DR),这与BM-MSCs相似。与BM-MSCs一样,UC-MSCs在LTC-IC试验中能有效支持CD34+脐带血细胞的生长。
这些数据表明,脐带华通氏胶来源的UC-MSCs有可能用于治疗,为脐带血造血干细胞的长期培养提供基质支持结构,以及在造血干细胞移植中共同移植基因相同、HLA匹配或不匹配的脐带血造血干细胞和UC-MSCs的可能性。