INSERM UMR 633, Laboratory of Surgical Research, Höopital Européen Georges Pompidou, Paris, France.
J Cell Mol Med. 2012 Jul;16(7):1544-52. doi: 10.1111/j.1582-4934.2011.01435.x.
Transplantation of allogeneic human embryonic stem cell-derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of adipose-derived stromal cells (ADSC). Peripheral blood mononuclear cells were collected from 40 patients with coronary artery disease (CAD) and nine healthy controls. Cardiac progenitors (CD15(+) Mesp1(+)) were generated as already reported from the I6 cell line treated with bone morphogenetic protein (BMP)-2. Adipose-derived stromal cells were obtained from abdominal dermolipectomies. We assessed the proliferative response of peripheral lymphocytes from patients and controls to cardiac progenitors cultured on a monolayer of ADSC, to allogeneic lymphocytes in mixed lymphocyte culture and to the T cell mitogen phytohemaglutin A in presence or absence of ADSC. Cardiac progenitors cultured on a monolayer of ADSC triggered a proliferation of lymphocytes from both patients and controls albeit lower than that induced by allogeneic lymphocytes. When cultured alone, ADSC did not induce any proliferation of allogeneic lymphocytes. When added to cultures of lymphocytes, ADSC significantly inhibited the alloantigen or mitogen-induced proliferative response. Compared to healthy controls, lymphocytes from patients presenting CAD expressed a decreased proliferative capacity, in particular to mitogen-induced stimulation. Adipose-derived stromal cells express an immunomodulatory effect that limits both alloantigen and mitogen-induced lymphocyte responses. Furthermore, lymphocytes from patients with CAD are low responders to conventional stimuli, possibly because of their age and disease-associated treatment regimens. We propose that, in combination, these factors may limit the in vivo immunogenicity of cardiac progenitors co-implanted with ADSC in patients with CAD.
同种异体人胚胎干细胞来源的心肌祖细胞移植会引发免疫反应。我们评估了脂肪来源的基质细胞（ADSC）的同时使用是否可以调节这种反应。从 I6 细胞系用骨形态发生蛋白（BMP）-2 处理后，我们已经从 40 名冠心病（CAD）患者和 9 名健康对照者中收集了外周血单核细胞。正如已经报道的那样，我们从 I6 细胞系中生成了心肌祖细胞（CD15（+）Mesp1（+））。从腹部脂肪切除术获得脂肪来源的基质细胞。我们评估了患者和对照者的外周淋巴细胞对在 ADSC 单层上培养的心肌祖细胞、混合淋巴细胞培养中的同种异体淋巴细胞以及 T 细胞有丝分裂原植物血球凝集素 A 的增殖反应。在 ADSC 单层上培养的心肌祖细胞引发了患者和对照者的淋巴细胞增殖，尽管低于同种异体淋巴细胞诱导的增殖。当单独培养时，ADSC 不会诱导任何同种异体淋巴细胞增殖。当添加到淋巴细胞培养物中时，ADSC 显著抑制同种异体抗原或有丝分裂原诱导的增殖反应。与健康对照者相比，患有 CAD 的患者的淋巴细胞表达出降低的增殖能力，特别是对有丝分裂原诱导的刺激。脂肪来源的基质细胞表达出免疫调节作用，限制了同种异体抗原和有丝分裂原诱导的淋巴细胞反应。此外，患有 CAD 的患者的淋巴细胞对常规刺激物的反应较低，可能是因为它们的年龄和与疾病相关的治疗方案。我们提出，这些因素可能会限制在 CAD 患者中与 ADSC 共同植入的心肌祖细胞的体内免疫原性。
