Concise Review: Towards the Clinical Translation of Induced Pluripotent Stem Cell-Derived Blood Cells-Ready for Take-Off

Abstract

Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have opened up a world of possibilities for regenerative medicine and novel cell-based therapeutics. Now, over a decade later, robust reprogramming and expansion and differentiation protocols have been developed, and iPSC-derived cells have been used in a wide variety of small and large animal models to treat many different diseases. Furthermore, the first iPSC derivatives are on their way into clinical trials. In this line, (i) GMP-compliant generation, cultivation, and differentiation, (ii) preclinical efficacy and safety, as well as (iii) ethical and regulatory compliance of stem cell research represent important aspects that need to be evaluated for proper clinical translation of iPSCs and their derivatives. In this review article, we provide an overview of the current advances and challenges of the clinical translation of iPSC-derived blood cells and highlight the most pressing problems that have to be overcome in the next years. Stem Cells Translational Medicine 2019;8:332-339.

Keywords: Blood; Clinical translation; Erythrocytes; GMP; Induced pluripotent stem cells; Macrophages; Platelets; Upscaling.

Figure 1

The clinical translation of induced pluripotent stem cell (iPSC)‐derived cells. iPSCs and their derived progeny hold great potential for their use in regenerative and personalized medicine. To achieve this aim, mature cells, for example, blood cells or fibroblasts, are collected from a patient (1) and reprogrammed into iPSCs using a GMP‐compliant protocol (2). After this, the cells have to go through several processes (3) including but not limited to: banking for future use and testing, expansion and differentiation in sufficient numbers via upscaling, for example, in bioreactors, purification, and functional analysis. Cells also have to go through tests by regulatory agencies regarding safety and compliance (4). Following certain cell release criteria, the cell products (5) can potentially be stored and infused back into the patient (6).

Figure 2

Localization of different macrophage subsets in different organs. Tissue macrophages play an important role in tissue homeostasis and can act as regulators in the innate immunity. Prominent examples for macrophages in different tissues are microglia in the brain, Kupffer cells in the liver, alveolar macrophages in the lung, and the intestinal macrophages. Considering the individual turnover and the ontogeny of the different macrophage subsets, generation and transplantation of induced pluripotent stem cell‐derived macrophages might be a future therapeutic approach for different diseases in which tissue macrophages are impaired.