Voisin Charlotte, Cauchois Ghislaine, Reppel Loïc, Laroye Caroline, Louarn Laetitia, Schenowitz Chantal, Sonon Paulin, Poras Isabelle, Wang Valentine, D Carosella Edgardo, Benkirane-Jessel Nadia, Moreau Philippe, Rouas-Freiss Nathalie, Bensoussan Danièle, Huselstein Céline
UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle de l'Université de Lorraine, Campus brabois-santé, Faculté de Médecine, 9 Avenue de la Forêt de Haye, BP 184, 54500 Vandoeuvre-lès-nancy, France.
UMS2008 IBSLor, Campus brabois-santé, 9 Avenue de la Forêt de Haye, BP20199, 54500 Vandoeuvre-lès-nancy, France.
J Clin Med. 2020 Feb 4;9(2):423. doi: 10.3390/jcm9020423.
Umbilical mesenchymal stem/stromal cells (MSCs), and especially those derived from Wharton's jelly (WJ), are a promising engineering tool for tissue repair in an allogeneic context. This is due to their differentiation capacity and immunological properties, like their immunomodulatory potential and paracrine activity. Hence, these cells may be considered an Advanced Therapy Medicinal Product (ATMP). The purpose of this work was to differentiate MSCs from WJ (WJ-MSCs) into chondrocytes using a scaffold and to evaluate, in vitro, the immunomodulatory capacities of WJ-MSCs in an allogeneic and inflammatory context, mimicked by IFN-γ and TNF-α priming during the chondrogenic differentiation.
Scaffolds were made from hydrogel composed by alginate enriched in hyaluronic acid (Alg/HA). Chondrogenic differentiation, immunological function, phenotype expression, but also secreted soluble factors were the different parameters followed during 28 days of culture.
During chondrocyte differentiation, even in an allogeneic context, WJ-MSCs remained unable to establish the immunological synapse or to induce T cell alloproliferation. Moreover, interestingly, paracrine activity and functional immunomodulation were maintained during cell differentiation.
These results show that WJ-MSCs remained hypoimmunogenic and retained immunomodulatory properties even when they had undergone chondrocyte differentiation.
脐带间充质干细胞(MSCs),尤其是源自华通氏胶(WJ)的间充质干细胞,是同种异体组织修复中一种很有前景的工程工具。这归因于它们的分化能力和免疫学特性,如免疫调节潜能和旁分泌活性。因此,这些细胞可被视为一种先进治疗医药产品(ATMP)。本研究的目的是使用支架将WJ中的MSCs(WJ-MSCs)分化为软骨细胞,并在体外评估WJ-MSCs在同种异体和炎症环境中的免疫调节能力,在软骨形成分化过程中通过IFN-γ和TNF-α引发来模拟这种环境。
支架由富含透明质酸的藻酸盐组成的水凝胶制成。软骨形成分化、免疫功能、表型表达以及分泌的可溶性因子是培养28天期间监测的不同参数。
在软骨细胞分化过程中,即使在同种异体环境中,WJ-MSCs仍无法建立免疫突触或诱导T细胞同种异体增殖。此外,有趣的是,在细胞分化过程中旁分泌活性和功能性免疫调节得以维持。
这些结果表明,即使WJ-MSCs已经经历软骨细胞分化,它们仍保持低免疫原性并保留免疫调节特性。