Abstract 10471: Both Adipose-Derived Stroma Cells and Coronary Artery Disease Positively Modulate the Immune Response to Human Embryonic Stem Cell-Derived Cardiac Progenitors
Background: Intra-myocardial transplantation of allogeneic human embryonic stem cell (ESC)-derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by concomitant use of adipose-derived stroma cells (ADSC) and patient-related factors such as age and coronary artery disease (CAD).
Methods: Peripheral blood MNC were collected from 9 healthy subjects and 40 patients with CAD. ADSC were obtained from dermolipectomies. SSEA-1+Mesp1+cardiac progenitors were generated from the I6 ESC line challenged with BMP-2. Lymphocyte proliferation in response to phytohemaglutin A (PHA), allogeneic lymphocytes or a mix of cardiac progenitors and ADSC was assessed by thymidine incorporation and CFSE staining. ADSC and cardiac progenitors were monitored by flow cytometry for the expression of MHC class I and II and CD80.
Results: ADSC expressed high levels of MHC class I molecules but neither MHC class II or CD80. They were weakly immunogenic and exerted an immunomodulatory effect by inhibiting lymphocyte proliferation induced by PHA (mean ± SD inhibition: 71.0%; ± 13.7%; at a 2:1 responder lymphocyte:ADSC ratio), and by allogeneic lymphocytes (64.3%; ± 7.7%; and 90.4%; ± 6.4%; at 2:1 and 1:1 ratios, respectively). Compared to undifferentiated ESC, cardiac progenitors expressed higher levels of MHC class I molecules (median fluorescence intensity: 19.3 vs.3.1), but neither MHC class II nor CD80. When co-cultured with ADSC, they triggered a weak lymphocyte proliferation with a median of 5,534 cpm [min-max: 1,972–17,184] which was significantly (p<0.001) lower than that induced by allogeneic lymphocytes in healthy subjects (16,579 cpm [15,636–21,388] or in CAD patients (18,795 cpm [7,116–41,244]). PHA-challenged lymphocytes from CAD patients had a reduced proliferation with a median of 15,591 [1,591–47,582] mitotic events over 72 hr compared with 58,852 [27,430–188,636] in < 50 yr healthy controls (p=0.0007) whereas those > 50 yr fell in an intermediate range (35,592 [10,420–60,765]).
Conclusion: Both the immunomodulatory effects of ADSC and a reduced immunoreactivity associated with CAD attenuate the immune response to ESC-derived cardiac progenitors which could favorably impact tolerance-inducing strategies.
- © 2010 by American Heart Association, Inc.