Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells.

Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells.
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DOI:
10.1111/j.1582-4934.2011.01435.x
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发表时间:
2012-07
影响因子:
5.3
通讯作者:
Chatenoud L
Chatenoud L
中科院分区:
医学2区
文献类型:
--
作者:
Calderon D;Planat-Benard V;Bellamy V;Vanneaux V;Kuhn C;Peyrard S;Larghero J;Desnos M;Casteilla L;Pucéat M;Menasché P;Chatenoud L

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同种异体人胚胎干细胞衍生的心脏祖细胞移植引发免疫应答。我们评估了这种反应是否可以通过同时使用脂肪源性基质细胞(ADSC)来调节。收集40例冠心病(CAD)患者和9例健康对照者的外周血单个核细胞。如已经报道的,从用骨形态发生蛋白(BMP)-2处理的I6细胞系产生心脏祖细胞(CD 15 + Mesp 1+)。脂肪来源的基质细胞从腹部真皮脂肪切除术获得。我们评估了患者和对照组外周淋巴细胞对ADSC单层上培养的心脏祖细胞、混合淋巴细胞培养中的同种异体淋巴细胞和存在或不存在ADSC的T细胞有丝分裂原植物血凝素A的增殖反应。在ADSC单层上培养的心脏祖细胞引发了患者和对照组淋巴细胞的增殖,尽管低于同种异体淋巴细胞诱导的增殖。单独培养时,ADSC不诱导任何同种异体淋巴细胞的增殖。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。与健康对照组相比,CAD患者的淋巴细胞增殖能力降低,特别是对丝裂原诱导的刺激。脂肪来源的基质细胞表达免疫调节作用,限制同种异体抗原和丝裂原诱导的淋巴细胞反应。此外,CAD患者的淋巴细胞对常规刺激的反应较低,这可能是因为他们的年龄和疾病相关的治疗方案。我们认为,结合这些因素可能会限制CAD患者中与ADSC共植入的心脏祖细胞的体内免疫原性。
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.
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