Christy Barbara A, Herzig Maryanne C, Delavan Christopher, Cantu Carolina, Salgado Christi, Bynum James A, Cap Andrew P
Coagulation & Blood Research, US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
Department of Molecular Medicine, UT Health San Antonio, San Antonio, Texas.
Transfusion. 2019 Apr;59(S2):1593-1600. doi: 10.1111/trf.15187.
Cellular therapeutic agents may benefit trauma patients by modulating the immune response to injury, and by reducing inflammation and vascular leakage. Administration of allogeneic mesenchymal stromal cells (MSCs) shows some benefit in preclinical and clinical trials, but less testing has been performed with other cell types. Human primary fibroblasts (FBs) were compared to MSCs in assays designed to evaluate MSCs to determine if these assays actually evaluate properties unique to MSCs or whether related cell types perform similarly.
MSC-related surface marker expression, tissue factor, and human leukocyte antigen-D related were evaluated by flow cytometry, and in vitro adipogenic and osteogenic differentiation potential were determined. Procoagulant activity was determined by thromboelastography. Two potency assays correlated with immunomodulation potential were utilized: the mixed lymphocyte reaction and indoleamine 2,3-dioxygenase enzyme activity assays.
Human primary FBs performed similarly to MSCs in assays designed to evaluate MSC characteristics and potency. Although similar for MSC-positive cell surface marker expression, FBs did not show robust adipose differentiation and expressed some level of markers not expected on MSCs.
Human primary FBs are very similar to human MSCs, at least in assays currently used to evaluate MSC potency. Preclinical and clinical testing are required to determine if FBs show similar activity to MSCs in vivo. If FBs show inferior activity in vivo, development of new MSC-specific potency assays will be necessary to evaluate properties relevant to their unique clinical benefits.
细胞治疗药物可能通过调节对损伤的免疫反应、减轻炎症和血管渗漏而使创伤患者受益。同种异体间充质基质细胞（MSCs）的给药在临床前和临床试验中显示出一定益处，但对其他细胞类型的测试较少。在旨在评估MSCs的试验中，将人原代成纤维细胞（FBs）与MSCs进行比较，以确定这些试验是否真的评估了MSCs特有的特性，或者相关细胞类型的表现是否相似。
通过流式细胞术评估与MSCs相关的表面标志物表达、组织因子和人白细胞抗原-D相关指标，并测定体外成脂和成骨分化潜能。通过血栓弹力图测定促凝活性。采用了两种与免疫调节潜能相关的效价测定方法：混合淋巴细胞反应和吲哚胺2,3-双加氧酶活性测定。
在旨在评估MSCs特性和效价的试验中，人原代FBs的表现与MSCs相似。虽然在MSCs阳性细胞表面标志物表达方面相似，但FBs未显示出强大的脂肪分化能力，且表达了一些在MSCs上未预期到的标志物水平。
人原代FBs与人类MSCs非常相似，至少在目前用于评估MSCs效价的试验中如此。需要进行临床前和临床试验，以确定FBs在体内是否表现出与MSCs相似的活性。如果FBs在体内表现出较低的活性，则有必要开发新的MSCs特异性效价测定方法，以评估与其独特临床益处相关的特性。
