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Experimental Replacement of the Surface Defect of Rat Hyaline Cartilage by a Cell-Engineered Construct

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Abstract

Background

Hyaline cartilage damage is an urgent problem for millions of people all over the world. A promising emerging area in the recovery of the hyaline cartilage is the transplantation a modified cell culture in combination with a biodegradable matrix.

Methods

In the present study, chondrogenic differentiation of bone marrow mesenchymal stem cells (MSCs) was achieved by adding 10 ng/mL of recombinant Tgfβ3 protein to the cells during culturing. The resulting cell culture was seeded on a poly(lactic acid) scaffold and transplanted into an experimentally model surface defect of rat hyaline cartilage.

Results

The applying of cellular engineering construct (CEC) with Tgfβ3 protein has led to significant recovery of damaged hyaline cartilage, in contrast to the control group, which has been confirmed by means of histology and scanning electron microscopy. Prolonged observation of the experimental groups treated with CEC has revealed that the initial injury is filled with the newly formed regenerate upon 90 days.

Conclusion

The designed CEC with recombinant Tgfβ3 leads to the formation of a regenerate resistant to external loads with a synthesized extracellular matrix of hyaline cartilage.

Lay Summary

Damages of hyaline cartilage is an urgent problem for millions of people around the world. Current methods of its treatment have not full solved the problem of recovery of the articular surface. At the present time, one of the most promising technique is to use tissue engineering. In our work, we have created a cell-engineered construct (CEC) based on a biodegradable polymer (polylactide) with a culture of mesenchymal stem cells (MSCs) modified with recombinant protein (transforming growth factor beta 3). Further, we transplanted this CEC to an experimental group of rats with a preliminarily created defect of the hyaline cartilage and observed the damage recovery for a long time. We found a decrease the damage size in the experimental group, which indicates the efficiency of this approach. In our future work, we plan to continue with larger animals (rabbits) and to produce out the CEC modification using both a recombinant protein and a lentivirus with increased expression of key genes for chondrogenesis tgfβ3 and sox9.

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Abbreviations

CEC:

cell-engineered construct

MSC:

mesenchymal stem cells

Tgfβ3:

transforming growth factor beta-3 cytokine

SEM:

scanning electron microscopy

RNA:

ribonucleic acid

ICRS:

International Cartilage Research Society

DNA:

deoxyribonucleic acid

cDNA:

coding DNA

iPSC:

induced pluripotent stem cells

PCR:

polymerase chain reaction

ECM:

extracellular matrix

SARA:

Smad Anchor for Receptor Activation

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Acknowledgements

The authors thank Dmitriy Veryaskin and Tatyana Lievina for their help in writing this article.

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Authors and Affiliations

  1. Vreden National Medical Research Center of Traumatology and Orthopedics, Street Academician Baykova house 8, 195427, St. Petersburg, Russia

    M. S. Bozhokin, S. A. Bozhkova, G. I. Netylko, D. G. Nakonechny & L. O. Anisimova

  2. Institute of Cytology, Russian Academy of Sciences, 194064, Tikhoretsky Ave., house 4, St. Petersburg, Russia

    M. S. Bozhokin, Y. A. Nashchekina & M. I. Blinova

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  1. M. S. Bozhokin
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  2. S. A. Bozhkova
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Correspondence to M. S. Bozhokin.

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Ethical Statement

The protocol of the animal experiments was approved by the Bioethical Committee for conducting biomedical research using animals

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Bozhokin, M.S., Bozhkova, S.A., Netylko, G.I. et al. Experimental Replacement of the Surface Defect of Rat Hyaline Cartilage by a Cell-Engineered Construct. Regen. Eng. Transl. Med. 7, 184–193 (2021). https://doi.org/10.1007/s40883-021-00205-2

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