Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies.
Human pluripotent stem cells (PSCs) are a leading candidate for cell-based therapies because of their capacity for unlimited self renewal and pluripotent differentiation. These advances have recently culminated in the first-in-human PSC clinical trials by Geron, Advanced Cell Technology and the Kobe Center for Developmental Biology for the treatment of spinal cord injury and macular degeneration. Despite their therapeutic promise, a crucial hurdle for the clinical implementation of human PSCs is their potential to form tumors in vivo. In this Perspective, we present an overview of the mechanisms underlying the tumorigenic risk of human PSC-based therapies and discuss current advances in addressing these challenges.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Medicine, Division of Cardiology Stanford University School of Medicine, Stanford, California 94305, USA.
Andrew S
AS
Lee
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Chad
C
Tang
National Center for Regenerative Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mahendra S
MS
Rao
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Irving L
IL
Weissman
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Medicine, Division of Cardiology Stanford University School of Medicine, Stanford, California 94305, USA.
Joseph C
JC
Wu
D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D065150:Cellular Reprogramming / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000009:adverse effects*