Cell-based artificial platelet production: historical milestones, emerging trends, and future directions

Abstract

Cell-based artificial platelet production has made remarkable progress over the past three decades, driven by the need for safe and stable platelet sources in the face of donor limitations and transfusion-related risks. This review provides a chronological overview of the evolution of in vitro platelet production from various cell sources (CD34+ hematopoietic stem cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and others) and highlights key advances in the field. We outline developments from the foundational experiments of the 1990s, through the introduction of iPSCs in the mid-2000s, to the adoption of three-dimensional culture and bioreactor technologies in the late 2010s and the emergence of clinical trials in the 2020s. In addition, we discuss future perspectives, including the role of advanced gene editing and scalable biomanufacturing technologies in accelerating clinical translation. This comprehensive review underscores the promise of artificial platelet production technologies for clinical applications and discusses the remaining challenges, such as scalability, cost-effectiveness, and regulatory hurdles. The recent completion of the first human clinical trials using iPSC-derived platelets marks a significant milestone, pointing to a future in which patient-specific or human leukocyte antigen-universal platelets may be transformed into transfusion medicine and regenerative therapies.

Keywords: Cell-based artificial platelets; Hematopoietic stem cells; Human pluripotent stem cells; Megakaryocytes.

Fig. 1

Changes in cell line statistics and usage trends. (A) Distribution of cell sources used across 41 studies from 1990s to 2020s. Of these, 46% used CD34+ hematopoietic stem cells (HSCs), 26% used induced pluripotent stem cells (iPSCs), 16% used embryonic stem cells (ESCs), and 5% each used adipose-derived cells and fibroblast cells. (B) Timeline illustrating how these cell sources were adopted in different periods. CD34+ HSCs have been widely used since the 1990s, while iPSCs rose to prominence in the 2010s following their initial development in 2006. See Table 1 for the full list of the 41 included studies.