Wharton's Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro
Wharton's Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro
复制标题
DOI：
10.1007/s12015-019-09907-1
复制
发表时间：
2019-12-01
影响因子：
4.8
通讯作者：
La Rocca, Giampiero
中科院分区：
文献类型：
--
作者：
Corsello, Tiziana;Amico, Giandomenico;La Rocca, Giampiero
终末期器官衰竭的治疗选择通常仅限于全器官移植。移植器官的耐受或排斥是由早期非特异性先天反应和特异性适应性反应共同驱动的。间充质基质细胞(MSCs)的使用被认为是一种很有前途的再生医学工具。人脐带(Huc)是一种容易获得的MSCs来源，不存在相关的伦理问题。此外，沃顿的凝胶来源的MSCs(WJ-MSCs)显示出一致的免疫调节特性，这可能有助于促进移植后宿主的免疫耐受。关于WJ-MSCs的原位表型资料很少。我们研究了HLAs、IDO、CD276/B7-H3等免疫相关分子在原位和体外培养的WJ-MSCs中的表达。用形态和生化技术来确定这些分子的表达。此外，我们还重点研究了CD276/B7-H3在T细胞增殖抑制中的可能作用。我们评估了WJ-MSCs在原位和伴随细胞培养中CD276/B7-H3的表达。WJ-MSCs能抑制混合淋巴细胞反应(MLR)中T细胞的增殖。此外，我们首次描述了CD276/B7-H3的特殊作用，因为在MLR中加入抗CD276/B7-H3抗体后，WJ-MSCs的免疫调节能力被取消。这些结果进一步详细说明了人WJ-MSCs的免疫调节特性和耐受诱导，特别是CD276/B7-H3是主要参与因素之一。这些数据进一步表明，WJ-MSCs在“支持型”再生医学方法中是调节局部免疫反应的有力工具。
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.