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

Journal of Cellular and Molecular Medicine

Damelys Calderon¹  Valérie Planat-Benard³  Valérie Bellamy¹  Valérie Vanneaux⁵  Chantal Kuhn⁴  Severine Peyrard²  Jéröome Larghero⁵  Michel Desnos¹  Louis Casteilla³  Michel Pucéat¹  Philippe Menasché¹ 

[1] INSERM UMR 633, Laboratory of Surgical Research, Höopital Européen Georges Pompidou, Paris, France;Höopital Européen Georges Pompidou, Epidemiology and Clinical Research Unit, INSERM CIE4, Paris, France;CNRS; UMR 5241 Métabolisme, Plasticité et Mitochondrie, Toulouse, France;INSERM U 1013, Paris, France;Assistance Publique-Höopitaux de Paris, Höopital Saint-Louis, Unit of Cell Therapy, Paris, France

关键词: immunogenicity;    cardiac progenitors;    embryonic stem cells;    alloreactivity;    T lymphocytes;    mesenchymal stem cells;    coronary artery disease;   

DOI  :  10.1111/j.1582-4934.2011.01435.x

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd