Immunogenetics Laboratory, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Pavia Cord Blood Bank, Immunohaematology and Transfusion Medicine Department, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Blood Transfus. 2014 Jan;12 Suppl 1(Suppl 1):s361-6. doi: 10.2450/2012.0144-12. Epub 2013 Jan 23.
Cord blood provides haematopoietic stem cells for allogeneic transplantation and, thanks to the naivety of its immune system, has several advantages over other sources of stem cells. In the transplantation setting, the presence of immunosuppressive human leucocyte antigen (HLA)-G molecules has been advocated to prevent both rejection and Graft-versus-Host disease. HLA-G is physiologically expressed throughout pregnancy and is contained in cord blood at birth. Moreover, it has recently been reported that not only cord blood mesenchymal cells, but also CD34+ cell progenies produce soluble HLA-G (sHLA-G). We tried to identify the largest producer of sHLA-G among 85 healthy cord blood donors at Pavia Cord Blood Bank, correlating the sHLA-G concentration with the HLA-G 14bp insertion/deletion (INS/DEL) genotype and CD34+ cell concentration.
We measured sHLA-G levels in 36 cord blood plasma stored at -20 °C for 2 months and 49 cord blood plasma stored at -196 °C for 4-6 years, by enzyme-linked immunosorbent assay. All cord blood donors were genotyped for the HLA-G 14bp INS/DEL polymorphism by polymerase chain reaction. For each cord blood unit, we measured the cell concentration by flow cytometry.
We did not find differences in sHLA-G levels between cord blood plasma aliquots stored for 4-6 years at -196 °C and cord blood plasma aliquots stored for 2 months at -20 °C. We observed a higher sHLA-G concentration in cord blood plasma donors who carried the HLA-G 14bp INS/INS genotype and had higher CD34+ cell concentrations (P=0.006).
This is the first report showing that the best cord blood stem cell donor is also the best sHLA-G producer, particularly if genetically characterized by the HLA-G 14bp INS/INS genotype. If the therapeutic role of sHLA-G molecules were to be finally established in the transplantation setting, our data suggest that cord blood plasma donors can provide a safe source of allogeneic sHLA-G immunosuppressive molecules ready for transfusion.
脐带血为异基因移植提供造血干细胞,并且由于其免疫系统的幼稚性,与其他干细胞来源相比具有若干优势。在移植环境中,存在免疫抑制性人白细胞抗原(HLA)-G 分子被认为可预防排斥和移植物抗宿主病。HLA-G 在整个妊娠期间生理性表达,并在出生时包含在脐带血中。此外,最近有报道称,不仅脐带血间充质细胞,而且 CD34+细胞祖细胞也产生可溶性 HLA-G(sHLA-G)。我们试图在帕维亚脐带血库的 85 位健康脐带血供体中确定 sHLA-G 的最大产生者,将 sHLA-G 浓度与 HLA-G14bp 插入/缺失(INS/DEL)基因型和 CD34+细胞浓度相关联。
我们通过酶联免疫吸附试验测量了 36 份在-20°C 下储存 2 个月的脐带血血浆和 49 份在-196°C 下储存 4-6 年的脐带血血浆中的 sHLA-G 水平。所有脐带血供体均通过聚合酶链反应对 HLA-G14bpINS/DEL 多态性进行了基因分型。对于每个脐带血单位,我们通过流式细胞术测量了细胞浓度。
我们没有发现在-196°C 下储存 4-6 年的脐带血血浆等分试样与在-20°C 下储存 2 个月的脐带血血浆等分试样之间 sHLA-G 水平存在差异。我们观察到携带 HLA-G14bpINS/INS 基因型且 CD34+细胞浓度较高的脐带血血浆供体具有更高的 sHLA-G 浓度(P=0.006)。
这是第一项表明最佳脐带血干细胞供体也是最佳 sHLA-G 产生者的报告,特别是如果在 HLA-G14bpINS/INS 基因型方面具有遗传特征。如果 sHLA-G 分子的治疗作用最终在移植环境中得到确立,我们的数据表明,脐带血血浆供体可以提供一种安全的同种异体 sHLA-G 免疫抑制分子来源,随时可供输注。