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  • Review Article
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Single-cell transcriptomics in tissue engineering and regenerative medicine

Nature Reviews Bioengineering volume 2, pages 101–119 (2024)Cite this article

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Abstract

Regenerative medicine and tissue engineering aim to promote functional rebuilding of damaged tissue. Comprehensively profiling cell identity, function and interaction in healthy tissues, as well as understanding how these change upon tissue disruption, such as that caused by injury, ageing or infection, is foundational to advancing tissue engineering and regenerative therapeutics. Tissue injury response is a highly dynamic process driven by complex interactions between immune and stromal cell populations, with dysregulation leading to deleterious fibrosis and chronic inflammation. Advances in single-cell RNA sequencing now allow in-depth mapping of the complex cellular response to injury and biomaterial implantation. In this Review, we first describe the fundamentals of sequencing and computational methods for the generation and analysis of high-dimensional single-cell RNA sequencing data sets. We then highlight how these methods can be applied to study tissue injury responses and guide the rational design of biomaterials and regenerative therapeutics.

Key points

  • Single-cell RNA sequencing (scRNA-seq) affords unprecedented resolution in profiling cellular transcriptomics by simultaneously detecting the expression of thousands of genes on an individual cell basis.

  • Tissue engineers can leverage scRNA-seq to comprehensively map healthy and perturbed (such as injured or diseased) tissue environments and explore cellular heterogeneity, gene expression shifts, differentiation trajectories and interaction networks.

  • Insights gained by scRNA-seq profiling of biological systems can be leveraged to guide the rational design of new biomaterials and regenerative therapeutics.

  • scRNA-seq can be used to characterize the host response to implanted engineered constructs or regenerative therapeutics and discern mechanisms of action (regenerative or fibrotic).

  • Sharing of data sets in public repositories, development of large-scale atlases and formation of dedicated consortiums promote low-cost accessibility, increase diversity and maximize exploration of generated scRNA-seq data sets.

  • Interdisciplinary teams of basic scientists, bioinformaticians, tissue engineers and clinicians should work together to connect computational approaches to outstanding biological questions, driving innovation of new regenerative therapeutics.

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Fig. 1: scRNA-seq workflow.
Fig. 2: Mapping tissue injury response.
Fig. 3: Application of scRNA-seq to biomaterials and tissue engineering.
Fig. 4: Large-scale data integration and analysis.

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Acknowledgements

This work was funded in part by the National Institutes of Health (NIH) Pioneer Award DP1AR076959 (to J.H.E.), Bloomberg~Kimmel Institute and Morton Goldberg Professorship (to J.H.E.). A.R. is funded through NSF GRFP DGE-1746891.

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  1. These authors contributed equally: Anna Ruta, Kavita Krishnan.

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  1. Translational Tissue Engineering Center and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Anna Ruta, Kavita Krishnan & Jennifer H. Elisseeff

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Ruta, A., Krishnan, K. & Elisseeff, J.H. Single-cell transcriptomics in tissue engineering and regenerative medicine. Nat Rev Bioeng 2, 101–119 (2024). https://doi.org/10.1038/s44222-023-00132-7

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