RESUMEN
BACKGROUND: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. METHODS: We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. RESULTS: In addition to macrophages, we found a high proportion of αß T cells in the coronary plaques. Most of these T cells lack high expression of CCR7 and L-selectin, indicating that they are primarily antigen-experienced memory cells. Notably, nearly one-third of these cells express the HLA-DRA surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated αß T cells (CD4Asunto(s)
Enfermedad de la Arteria Coronaria
, Placa Aterosclerótica
, Linfocitos T
, Antígenos
, Células Clonales/inmunología
, Enfermedad de la Arteria Coronaria/inmunología
, Células Endoteliales
, Epítopos
, Cadenas alfa de HLA-DR
, Humanos
, Activación de Linfocitos
, Placa Aterosclerótica/inmunología
, Linfocitos T/inmunología
Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Vasos Coronarios/diagnóstico por imagen , Medición de Riesgo , Calcificación Vascular/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Radioisótopos de Flúor , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Tomografía de Emisión de PositronesRESUMEN
The growing number of victims of "stem cell tourism," the unregulated transplantation of stem cells worldwide, has raised concerns about the safety of stem cell transplantation. Although the transplantation of differentiated rather than undifferentiated cells is common practice, teratomas can still arise from the presence of residual undifferentiated stem cells at the time of transplant or from spontaneous mutations in differentiated cells. Because stem cell therapies are often delivered into anatomically sensitive sites, even small tumors can be clinically devastating, resulting in blindness, paralysis, cognitive abnormalities, and cardiovascular dysfunction. Surgical access to these sites may also be limited, leaving patients with few therapeutic options. Controlling stem cell misbehavior is, therefore, critical for the clinical translation of stem cell therapy. External beam radiation offers an effective means of delivering targeted therapy to decrease the teratoma burden while minimizing injury to surrounding organs. Additionally, this method avoids genetic manipulation or viral transduction of stem cells-which are associated with additional clinical safety and efficacy concerns. Here, we describe a protocol to create pluripotent stem cell-derived teratomas in mice and to apply external beam radiation therapy to selectively ablate these tumors in vivo.