title: Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells.
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.
authors: INSERM UMR 633, Laboratory of Surgical Research, Höopital Européen Georges Pompidou, Paris, France.
authors: Damelys
authors: D
authors: Calderon
authors: Valérie
authors: V
authors: Planat-Benard
authors: Valérie
authors: V
authors: Bellamy
authors: Valérie
authors: V
authors: Vanneaux
authors: Chantal
authors: C
authors: Kuhn
authors: Severine
authors: S
authors: Peyrard
authors: Jérôme
authors: J
authors: Larghero
authors: Michel
authors: M
authors: Desnos
authors: Louis
authors: L
authors: Casteilla
authors: Michel
authors: M
authors: Pucéat
authors: Philippe
authors: P
authors: Menasché
authors: Lucienne
authors: L
authors: Chatenoud
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003324:Coronary Artery Disease / Q000503:physiopathology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D006321:Heart; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D008934:Mitogens; D033581:Stem Cell Transplantation / Q000379:methods*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D008934:Mitogens