Modulation and Imaging of Cardiac Stem Cell Therapy
Final Report Abstract
In summary, the study demonstrates that a short course of costimulation-adhesion blockade treatment is sufficient to induce engraftment of xenogeneically transplanted hESC derivatives in both injured and healthy tissues, and to promote cardiac protection. Application of hESC and iPSC-derived cells holds great promise for cell replacement therapies in man, with clinical trials already ongoing in USA/Europe. This study represents an important step forward in overcoming the immunologic barriers that have continued to hamper the full realization of highly promising pluripotent stem cell-based therapies41, and that must be addressed before their eventual clinical application. It was surprising to see that traditional immunosuppressive therapies used to prevent solid organ rejection, such as calcineurin inhibitors and corticosteroids, are insufficient to prevent human embryonic stem cell rejection following transplantation. We were able to demonstrate that a short-course, dualagent regimen that prevents optimal T cell activation is sufficient to promote the robust and long-term survival of embryonic stem cell derivatives in both healthy and injured tissues in mouse models. The superior response of the transplanted cells to the costimulation-adhesion therapy may be attributed to its repression of both adaptive and innate immunity, which is likely to aid in mitigating the tissues’ rejection of these characteristically immunogenic cells. This led to both local and systemic upregulation of T cell immunoglobulin and mucin domain 3 (TIM3), a Th-1-specific cell surface protein, in addition to an overall reduction of pro-inflammatory cytokines. The results of this study published in STEM CELLS 2013 were featured on Stanford SCOPE (http://scopeblog.stanford.edu/2013/08/19/shushing-t-cells-promotes-acceptance-of-stem-celltherapies-say-stanford-researchers/) and other news outlets (http://www.prweb.com/releases/2013/8/prweb11033138.htm).
Publications
- Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging.Circ Res. 2012 Dec 7
Wang Y, Zhang WY, Hu S, Lan F, Lee AS, Huber B, Lisowski L, Liang P, Huang M, de Almeida PE, Won JH, Sun N, Robbins RC, Kay MA, Urnov FD, Wu JC
- In Vivo Functional and Transcriptional Profiling of Bone Marrow Stem Cells After Transplantation Into Ischemic Myocardium. ArteriosclerThrombVasc Biol. 2012 Jan
Sheikh AY, Huber BC, Narsinh KH, Spin JM, van der Bogt K, de Almeida PE, Ransohoff KJ, Kraft DL, Fajardo G, Ardigo D, Ransohoff J, Bernstein D, Fischbein MP, Robbins RC, Wu JC
- Microfluidic single-cell analysis shows that porcine induced pluripotent stem cell-derived endothelial cells improve myocardial function by paracrine activation.Circ Res. 2012 Sep 14
Gu M, Nguyen PK, Lee AS, Xu D, Hu S, Plews JR, Han L, Huber BC, Lee WH, Gong Y, de Almeida PE, Lyons J, Ikeno F, Pacharinsak C, Connolly AJ, Gambhir SS, Robbins RC, Longaker MT, Wu JC
