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A Single Administration of Synthetic Artificial Stem Cells (SASC) Attenuates Osteoarthritis Progression

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Abstract

Purpose

Osteoarthritis (OA) is a highly prevalent joint disease for which common therapies may provide symptomatic relief but have failed to provide a curative solution. There has been a growing interest in disease-modifying therapies, such as the use of stem cells and bioactive factors in treating OA. The synthetic artificial stem cell (SASC) system has previously been introduced as one such disease-modifying therapy: designed to mimic the paracrine effect of biological stem cells but with the added ability to engineer the composition and tailor it to different tissue types.

Methods

In the present study, the efficacy of a single intra-articular injection was evaluated across three doses (1, 3, or 5 million) of SASC cells in a collagenase-induced OA rat model. Inflammation was monitored by joint swelling through the 63 day treatment period and structural and functional cartilage regeneration outcomes as well as local immune and inflammatory outcomes were evaluated by histology, nano-indentation of the gross cartilage, and immunohistochemistry. Further, in vitro SASC modulation of the NF-κβ pathway was observed by monitoring various upstream and downstream gene expression profiles along the pathway.

Results

A single administration of 3 million and 5 million SASC cells reduced knee swelling attenuates cartilage degeneration as observed by Safranin O staining, compared to the OA control. Further, major genes along the NF-κβ pathway were significantly modulated by SASC to a similar extent compared to ADSC control.

Conclusion

The present study demonstrated that SASC Cells have a dose-dependent response in attenuating collagenase-induced OA progression and effectively modulates the major inflammatory pathway involved in the pathogenesis of OA.

Lay Summary

In this study, we investigated the efficacy of synthetic artificial stem cells (SASC) in treating osteoarthritis (OA). Different doses of SASC cells were injected into rats with OA. Higher doses of SASC cells reduced knee swelling, protected against cartilage degeneration, and modulated the inflammatory NF-κβ pathway. This work highlights potential of SASC cells as a curative treatment for OA.

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Data Availability

Published data will be open-access and available publicly.

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Acknowledgements

This work was supported by NIH Grant T32 AR079114. Support from the Raymond and Beverly Sackler Center is gratefully acknowledged.

The authors gratefully thank the Center for Comparative Medicine at University of Connecticut Health Center. We also thank Dr. Chia-Ling Kuo of the Connecticut Convergence Institute for Translation in Regenerative Engineering for her help with statistical analysis.

Funding

National Institutes of Health grant DP1AR068147 (CTL)

National Institutes of Health grant T32 AR079114 (CTL)

Author information

Authors and Affiliations

  1. Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, USA

    Shiv Shah, Maumita Bhattacharjee, Ho-Man Kan, Rachel L. Marchini, Lakshmi S. Nair & Cato T. Laurencin

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

    Shiv Shah, Maumita Bhattacharjee, Ho-Man Kan, Rachel L. Marchini, Lakshmi S. Nair & Cato T. Laurencin

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

    Shiv Shah, Rachel L. Marchini & Cato T. Laurencin

  4. Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT, USA

    Tannin A. Schmidt & Cato T. Laurencin

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

    Lakshmi S. Nair & Cato T. Laurencin

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

    Lakshmi S. Nair & Cato T. Laurencin

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

    Lakshmi S. Nair & Cato T. Laurencin

  8. Institute of Materials Science, University of Connecticut, Storrs, CT, USA

    Cato T. Laurencin

  9. Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT, USA

    Cato T. Laurencin

Authors
  1. Shiv Shah
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  7. Cato T. Laurencin
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Contributions

Conceptualization: SS, LSN, CTL.

Methodology: SS, TAS, CTL

Investigation: SS, MB, HMK

Analysis: SS

Funding acquisition: CTL

Writing: SS, MB, HMK, RLM, TAS, LSN, CTL

Corresponding author

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., H.M.K., L.S.N., C.T.L) entitled The Synthetic Artificial Stem Cell. L.S.N has the following competing financial interest: Soft tissue regeneration/Biorez. C.T.L. has the following competing financial interests: Mimedx, Alkermes Company, Biobind, Soft tissue regeneration/Biorez, Healing Orthopedic Technologies-Bone.

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Shah, S., Bhattacharjee, M., Kan, HM. et al. A Single Administration of Synthetic Artificial Stem Cells (SASC) Attenuates Osteoarthritis Progression. Regen. Eng. Transl. Med. 10, 78–92 (2024). https://doi.org/10.1007/s40883-023-00307-z

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