Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton’s jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of immune-related molecules, such as HLAs, IDO, CD276/B7-H3, and others, both in situ (HUC) and in in vitro-cultured WJ-MSCs. Morphological and biochemical techniques were used to define the expression of such molecules. In addition, we focused on the possible role of CD276/B7-H3 on T cells proliferation inhibition. We assessed CD276/B7-H3 expression by WJ-MSCs both in situ and alongside cell culture. WJ-MSCs were able to suppress T cell proliferation in mixed lymphocyte reaction (MLR). Moreover, we describe for the first time a specific role for CD276/B7-H3, since the immunomodulatory ability of WJ-MSCs was abolished upon anti-CD276/B7-H3 antibody addition to the MLR. These results further detail the immune regulation properties and tolerance induction exerted by human WJ-MSCs, in particular pointing to CD276/B7-H3 as one of the main involved factors. These data further suggest WJ-MSCs as potent tools to modulate local immune response in “support-type” regenerative medicine approaches.

中文翻译：

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来自人脐带的沃顿商学院的果冻间质基质细胞：原位和体外免疫调节分子的特写。

终末期器官衰竭的治疗选择通常仅限于整个器官移植。早期非特异性先天性和特异性适应性反应都驱动移植器官的耐受或排斥。间充质基质细胞（MSCs）的使用被认为是再生医学中有希望的工具。人脐带（HUC）是易于获得的MSC来源，没有相关的伦理问题。此外，沃顿商学院的果冻来源的MSC（WJ-MSC）表现出一致的免疫调节功能，可能有助于在移植后促进宿主的免疫耐受。关于WJ-MSC的表型的数据很少。我们研究了与免疫有关的分子（例如HLA，IDO，CD276 / B7-H3等）的原位（HUC）和体外培养的WJ-MSC的表达。使用形态学和生化技术来定义此类分子的表达。此外，我们集中于CD276 / B7-H3对T细胞增殖抑制的可能作用。我们评估了WJ-MSC在原位和细胞培养中的CD276 / B7-H3表达。WJ-MSC能够抑制混合淋巴细胞反应（MLR）中的T细胞增殖。此外，我们首次描述了CD276 / B7-H3的特定作用，因为在加入MLR的抗CD276 / B7-H3抗体后，WJ-MSC的免疫调节能力消失了。这些结果进一步详述了人WJ-MSC施加的免疫调节特性和耐受诱导，特别是指出CD276 / B7-H3是主要参与因素之一。