Cátedra de Citología, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires, Argentina.
LIAN-CONICET, FLENI Escobar, Buenos Aires, Argentina.
Cell Transplant. 2021 Jan-Dec;30:963689721993774. doi: 10.1177/0963689721993774.
In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton's jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR-. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.
在正常生理条件下，功能性表皮屏障的恢复效率非常高；然而，当它失效时，主要后果之一是慢性溃疡性皮肤缺损，这是糖尿病最常见的并发症之一。大多数这些慢性静脉溃疡不能通过常规治疗愈合，导致患者出现感染和并发症。基于使用自体间充质干细胞 (MSC) 的治疗已取得成功；然而，其实施带来了并发症。脐带为沃顿胶组织中的成人间充质干细胞 (ucMSC) 提供了无限的来源，具有相同的临床应用相关特征，并避免了困难。最近，它被来自 ucMSC 的一个特定亚群所特征化，即分化间充质细胞 (DMC)。该亚群表达人类白细胞抗原-G (HLA-G) 分子，这是一种强大的免疫抑制检查点，以及血管内皮生长因子 (VEGF)，这是最有效的血管生成因子。考虑到开发更有效的伤口治疗方法的重要性，特别是溃疡性皮肤病变，我们分析了 DMC 的安全性、疗效和治疗潜力。通过免疫组织化学，选择了脐带 HLA-G 和 VEGF 阳性的样本。流式细胞术显示，DMC 亚群中有 90%是 HLA-G+、CD44+、CD73+、CD29+、CD105+、CD90+和 HLA-DR-。逆转录-聚合酶链反应显示，所有 DMC 亚群都表达 HLA-G。在与 DMC 共培养时，外周血单核细胞的增殖被抑制了 50%。在异种移植移植试验中，DMC 改善了伤口愈合，免疫功能正常的小鼠中没有移植细胞排斥的迹象。这项研究证实，HLA-G 允许同种异体细胞移植，而 VEGF 对于恢复血液供应的失败是至关重要的。DMC 对伤口愈合有积极影响，通过促进皮肤病变中的局部血管生成。DMC 在再生医学中可能发挥非常重要的作用，并可能成为一种新的用于伤口愈合的同种异体细胞治疗工具。
