4.6 Article

Single-Cell RNA Sequencing of Human Pluripotent Stem Cell-Derived Macrophages for Quality Control of The Cell Therapy Product

Journal

FRONTIERS IN GENETICS
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.658862

Keywords

single-cell RNA sequencing; Pluripotent stem cell; macrophage; quality control; cell therapy product

Funding

  1. KCDC [2020-NG-018, 2020-NG-019, 2019-NI-092-00]
  2. Korea Centers for Disease Control and Prevention [2020-02-09-C-A]

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Macrophages play important roles in maintaining tissue homeostasis, immune response, and tissue repair. They have potential therapeutic applications in treating inflammatory disorders and cancer. Human pluripotent stem cell (hPSC)-derived macrophages are considered as an alternative source of primary macrophages for clinical use. However, the quality of these hPSC-derived macrophages is still unclear. In this study, we evaluated the biological homogeneity of hPSC-derived macrophages and demonstrated the usefulness of single cell RNA sequencing data in quality control of cell-based therapy products.
Macrophages exhibit high plasticity to achieve their roles in maintaining tissue homeostasis, innate immunity, tissue repair and regeneration. Therefore, macrophages are being evaluated for cell-based therapeutics against inflammatory disorders and cancer. To overcome the limitation related to expansion of primary macrophages and cell numbers, human pluripotent stem cell (hPSC)-derived macrophages are considered as an alternative source of primary macrophages for clinical application. However, the quality of hPSC-derived macrophages with respect to the biological homogeneity remains still unclear. We previously reported a technique to produce hPSC-derived macrophages referred to as iMACs, which is amenable for scale-up. In this study, we have evaluated the biological homogeneity of the iMACs using a transcriptome dataset of 6,230 iMACs obtained by single-cell RNA sequencing. The dataset provides a valuable genomic profile for understanding the molecular characteristics of hPSC-derived macrophage cells and provide a measurement of transcriptomic homogeneity. Our study highlights the usefulness of single cell RNA-seq data in quality control of the cell-based therapy products.

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