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Musculoskeletal Tissue Regeneration: the Role of the Stem Cells

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Abstract

Ligament, cartilage, and meniscus injuries often have poor healing due to low vascularity and low proliferative abilities of the resident cells. Drawbacks with conventional treatment methodologies have prompted interest in a new approach we term “Regenerative Engineering” to regenerate orthopaedic tissues. The work of cells is of central importance in the Regenerative Engineering paradigm. In this regard, both differentiated cells and stem cells such as bone marrow stromal cells have been studied as sources for orthopaedic tissue regeneration. In addition, other stem cells such as those derived from peripheral blood, synovium, adipose, and other extraembryonic sources have been isolated and characterized and subsequently investigated for regenerating various orthopaedic tissues. In this review, recent developments in the stem cell-mediated regeneration of ligament, cartilage, and menisci are discussed.

Lay Summary

Most orthopaedic tissue ailments originate from trauma or degenerative diseases. Commonly utilized strategies in clinical settings have shortcomings such as poor or incomplete healing. By converging advanced materials science with stem cells, growth factors/small molecules, and developmental biology, regenerative engineering is expected to provide strategies for orthopaedic tissue regeneration. In this review, we discuss various cell sources that have been isolated, characterized, and studied for regenerating orthopaedic tissues. Some of the underlying molecular mechanisms involved in those cells are also discussed. In addition, various approaches based on those cell sources for regenerating ligament, cartilage, and meniscus tissues are reported. In the future, cell-based approaches discussed in this review need to be combined with other salient aspects of regenerative engineering to facilitate activation of multiple signaling pathways required for tissue regeneration. Via such a holistic approach, we anticipate regeneration of ligaments, cartilage, and meniscus with features similar to that of native tissue.

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Funding

The authors gratefully acknowledge funding from the Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, NIH R01AR063698, and NIH DP1 AR068147.

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  1. Ganesh Narayanan and Maumita Bhattacharjee contributed equally to the manuscript.

Authors and Affiliations

  1. Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Ganesh Narayanan, Maumita Bhattacharjee, Lakshmi S. Nair & Cato T. Laurencin

  2. Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Ganesh Narayanan, Maumita Bhattacharjee, Lakshmi S. Nair & Cato T. Laurencin

  3. Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Ganesh Narayanan, Maumita Bhattacharjee, Lakshmi S. Nair & Cato T. Laurencin

  4. Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Cato T. Laurencin

  5. Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Cato T. Laurencin

  6. Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Lakshmi S. Nair & Cato T. Laurencin

  7. Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Lakshmi S. Nair & Cato T. Laurencin

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  1. Ganesh Narayanan
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Narayanan, G., Bhattacharjee, M., Nair, L.S. et al. Musculoskeletal Tissue Regeneration: the Role of the Stem Cells. Regen. Eng. Transl. Med. 3, 133–165 (2017). https://doi.org/10.1007/s40883-017-0036-9

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