Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.
Yongshun LinNoriko SatoSogun HongKenta NakamuraElisa A FerranteZu Xi YuMarcus Y ChenDaisy S NakamuraXiulan YangRandall R ClevengerTimothy J HuntJoni L TaylorKenneth R JeffriesKaren J KeeranLauren E NeidigAtul MehtaRobin SchwartzbeckShiqin Judy YuConor KellyKeron NavarengomKazuyo TakedaStephen S AdlerPeter L ChoykeJizhong ZouCharles E MurryManfred BoehmCynthia E DunbarPublished in: Cell stem cell (2024)
Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.
Keyphrases
- induced pluripotent stem cells
- bone marrow
- positron emission tomography
- cell therapy
- computed tomography
- stem cells
- platelet rich plasma
- left ventricular
- magnetic resonance
- heart failure
- preterm infants
- hematopoietic stem cell
- risk assessment
- magnetic resonance imaging
- genome wide
- cross sectional
- climate change
- gestational age
- wound healing