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Classes of Stem Cells: From Biology to Engineering

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Abstract

Purpose

The majority of adult tissues are limited in self-repair and regeneration due to their poor intrinsic regenerative capacity. It is widely recognized that stem cells are present in almost all adult tissues, but the natural regeneration in adult mammals is not sufficient to recover function after injury or disease. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). Here, we have defined a fourth fully engineered class: the synthetic artificial stem cell (SASC). This review aims to discuss the applications of these stem cell classes in musculoskeletal regenerative engineering.

Method

We screened articles in PubMed and bibliographic search using a combination of keywords. Relevant and high-cited articles were chosen for inclusion in this narrative review.

Results

In this review, we discuss the different classes of stem cells that are biologically derived (ESCs and MSCs) or semi-engineered/engineered (iPSCs, SASC). We also discuss the applications of these stem cell classes in musculoskeletal regenerative engineering. We further summarize the advantages and disadvantages of using each of the classes and how they impact the clinical translation of these therapies.

Conclusion

Each class of stem cells has advantages and disadvantages in preclinical and clinical settings. We also propose the engineered SASC class as a potentially disease-modifying therapy that harnesses the paracrine action of biologically derived stem cells to mimic regenerative potential.

Lay Summary

The majority of adult tissues are limited in self-repair and regeneration, even though stem cells are present in almost all adult tissues. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). Here, we have defined a fourth, fully engineered class: the synthetic artificial stem cell (SASC). In this review, we discuss the applications of each of these stem cell classes in musculoskeletal regenerative engineering. We further summarize the advantages and disadvantages of using each of these classes and how they impact the clinical translation of these therapies.

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Acknowledgements

Support from NIH/NIAMS T32 AR079114 (to CTL), NSF EFRI-Bioflex 1332329 (to CTL), Building Infrastructure Leading to Diversity (BUILD) TL4GM118971 (to CTL), and Raymond and Beverly Sackler Center for Biomedical, Biological, Physical, and Engineering Sciences is gratefully acknowledged. Original images were created using Biorender.

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Authors and Affiliations

  1. The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, 263 Farmington Avenue, Farmington, CT, 06030-3711, USA

    Shiv Shah, Debolina Ghosh, Takayoshi Otsuka & Cato T. Laurencin

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

    Shiv Shah, Takayoshi Otsuka & Cato T. Laurencin

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

    Shiv Shah & Cato T. Laurencin

  4. Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, USA

    Cato T. Laurencin

  5. Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA

    Cato T. Laurencin

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

    Cato T. Laurencin

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  1. Shiv Shah
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  2. Debolina Ghosh
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  3. Takayoshi Otsuka
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  4. Cato T. Laurencin
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The manuscript was conceptualized and written through the contributions of all authors. All authors have approved the final version of the manuscript.

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Correspondence to Cato T. Laurencin.

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Competing Interests

University of Connecticut has filed a patent application on behalf of the inventors (S.S., C.T.L) entitled The Synthetic Artificial Stem Cell. C.T.L. has the following competing financial interests: Mimedx, Alkermes Company, Biobind, Soft tissue regeneration/Biorez, and Healing Orthopedic Technologies-Bone.

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Shah, S., Ghosh, D., Otsuka, T. et al. Classes of Stem Cells: From Biology to Engineering. Regen. Eng. Transl. Med. (2023). https://doi.org/10.1007/s40883-023-00317-x

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