Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory agents in rat model of rheumatoid arthritis

Abstract

To compare human adipose tissue mesenchymal stem cells (AT-MSCs) and etanercept as immunomodulatory agents for collagen-induced arthritis (CIA). CIA was induced by rats’ immunization with collagen type II (CII) in complete Freund’s adjuvant in days 0 and 7. Before the onset of CIA, prevention group received five doses of AT-MSCS intraperitoneally. After establishment of arthritis, rats received either five doses of AT-MSCs or phosphate-buffered saline (PBS) intraperitoneally or six doses of etanercept subcutaneously. Clinical and histopathological evaluation were performed in all groups; serum levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and anti-collagen II were assessed by enzyme-linked immunosorbent assay (ELISA). A total percent of autoreactive T and regulatory T (Treg) cells were quantified using spleen immune histochemical analysis. AT-MSCs were able to delay the onset of CIA, suppress the ongoing clinical and histopathological signs, decrease serum levels of TNF-α and anti-collagen type II, and downregulate the autoreactive T cells as etanercept. AT-MSCs were more potent in Treg cells upregulation, producing high serum levels of IL10. AT-MSCs might have a therapeutic effect in CIA via their potency in immune cell education, representing an effective new promising approach in rheumatoid arthritis in human.

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Abbreviations

AT-MSCs:

Adipose tissue mesenchymal stem cells

BM-MSCs:

Bone marrow–derived MSCs

CIA:

Collagen-induced arthritis

CII:

Collagen type II

DMARDs:

Disease-modifying anti-rheumatic drugs

DMEM:

Dulbecco’s Modified Eagle’s Medium

ELISA:

Enzyme-linked immunosorbent assay

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

FOXP3:

Forkhead box P3

IL-10:

Interleukin-10

mAb:

Monoclonal antibodies

MERC:

Medical Experimental Research Center

MSCs:

Mesenchymal stem cells

PBS:

Phosphate-buffered saline

RA:

Rheumatoid arthritis

TNF-α:

Tumor necrosis factor-α

Treg:

Regulatory T cells

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Acknowledgments

The authors would like to thank all members of MERC and Medical Biochemistry Department at Mansoura University for their helpful guidance and support.

Funding

This work was totally funded by authors.

Availability of data and materials

The data used to support the findings of this study are available from the corresponding author upon request.

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Contributions

SHE, MA, and MAM conceived, designed, supervised, and commented on all the drafts of this paper. HEG, MAm, HAA, SF, and AL conducted the overall experiments and participated in the clinical data collection, analysis, laboratory, and histopathological investigations. HEG and AL contributed to the data interpretation and helped in manuscript completion. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Heba El-Gendy.

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The authors declare that they have no competing interests.

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The study was authorized by animal ethics committee of Mansoura University.

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Highlights

• AT-MSCs could delay and suppress both clinical and histopathological features of rat CIA.

• AT-MSCs were proven to be an immunomodulatory agent that reestablish immunologic tolerance in CIA.

• AT-MSCs may require sufficient time for migration to lymphoid organs to target the immune cells.

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El-Gendy, H., Hawass, S.ED., Awad, M. et al. Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory agents in rat model of rheumatoid arthritis. Immunol Res 68, 255–268 (2020). https://doi.org/10.1007/s12026-020-09132-w

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Keywords

  • Mesenchymal stem cells
  • CIA
  • Rheumatoid arthritis
  • Etanercept
  • Regulatory T cells