Current Progress of hiPSCs‐based Therapy in non‐human Primates and Human Clinical Trials

Abstract

Since the first successful creation of mouse induced pluripotent stem cells (miPSCs) in 2006 by Dr. Shinya Yamanaka and the subsequent generation of human iPSC (hiPSCs) in 2007, independently, by Dr. Yamanaka and Dr. James Thomas, iPSCs have been drawing exceptional attention compared to human embryonic stem cells (hESCs), mainly because hiPSCs can be easily generated from virtually any embryonic or adult somatic cells of the body without demolishing human embryos, thus offering an immense promise for personalized regenerative medicine; In contrast to the fetal or adult stem cells (FSCs, ASCs), hiPSCs demonstrate unlimited abilities of self‐renewal and differentiation potency to become almost all somatic cells in the body. Over the past 14 years, about 17,364 papers regarding iPSCs have been published (PubMed search between 2006/01/01 and 2019/11/12), which cover a wide spectrum ranging from in vitro basic researches, computer modeling, in vivo animal and non‐human primate studies to human clinical trials. Up to the present, systemic protocols involving iPSC reprogramming, purification, large‐scale culture expansion, and lineage‐specific differentiation have been successfully developed or optimized to increase the efficiencies of production. Meanwhile, iPSCs and its derivatives have also been widely utilized for mechanistic studies of cellular and molecular development, disease modeling, new drug discovery and toxicity testing. Along with it, a vast type of small‐, large‐animals, and non‐human primate‐models have been exploited to test the therapeutic potentials of these cells in treatments of numerous human diseases. More excitingly, 53 clinical trials of iPSC‐based therapy have been registered in the https://clinicaltrials.gov as of today. Although most of them are still in the “Recruiting” stage, the substantial increase of the registered trials signifies a critical movement towards future clinical practice in all aspects, such as ethical and regulatory compliance under surveillance of U.S. Food and Drug Administration (FDA), quality control of cell products, current good manufacturing practice (cGMP)‐guided cell storage, culture, purification, and lineage‐specific differentiation as well as in vivo assessments of efficacy and safety in a short and long‐term follow‐up. In this talk, we will present an overview of the current progresses, challenges, and concerns of hiPSC‐based treatments for various major diseases (e.g. neural disorders, cardiovascular diseases, and diabetes) using animal models; especially, we will focus on the recent progress acquired from the studies of non‐human primates and human subjects.Support or Funding InformationThis work was supported by the National Institute of Health (NIH 1R15HL140528), the Virginia Tech Commonwealth Health Research Board (CHRB, HE208‐09‐16), and the IRC seed grant from the College of Veterinary Medicine at Virginia Tech.