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Stem cell research & therapy2021; 12(1); 570; doi: 10.1186/s13287-021-02624-y

Immune response to allogeneic equine mesenchymal stromal cells.

Abstract: Mesenchymal stromal cells (MSCs) are believed to be hypoimmunogeneic with potential use for allogeneic administration. Bone marrow was harvested from Connemara (n = 1), Standardbred (n = 6), and Thoroughbred (n = 3) horses. MSCs were grouped by their level of expression of major histocompatibility factor II (MHC II). MSCs were then sub-grouped by those MSCs derived from universal blood donor horses. MSCs were isolated and cultured using media containing fetal bovine serum until adequate numbers were acquired. The MSCs were cultured in xenogen-free media for 48 h prior to use and during all assays. Autologous and allogeneic MSCs were then directly co-cultured with responder leukocytes from the Connemara horse in varying concentrations of MSCs to leukocytes (1:1, 1:10, and 1:100). MSCs were also cultured with complement present and heat-inactivated complement to determine whether complement alone would decrease MSC viability. MSCs underwent haplotyping of their equine leukocyte antigen (ELA) to determine whether the MHC factors were matched or mismatched between the donor MSCs and the responder leukocytes. All allogeneic MSCs were found to be ELA mismatched with the responder leukocytes. MHC II-low and universal blood donor MSCs caused no peripheral blood mononuclear cell (PBMC) proliferation, no increase in B cells, and no activation of CD8 lymphocytes. Universal blood donor MSCs stimulated a significant increase in the number of T regulatory cells. Neutrophil interaction with MSCs showed that universal blood donor and MHC II-high allogeneic MSCs at the 6 h time point in co-culture caused greater neutrophil activation than the other co-culture groups. Complement-mediated cytotoxicity did not consistently cause MSC death in cultures with active complement as compared to those with inactivated complement. Gene expression assays revealed that the universal blood donor group and the MHC II-low MSCs were more metabolically active both in the anabolic and catabolic gene categories when cultured with allogeneic lymphocytes as compared to the other co-cultures. These upregulated genes included CD59, FGF-2, HGF, IDO, IL-10, IL-RA, IL-2, SOX2, TGF-β1, ADAMSTS-4, ADAMSTS-5, CCL2, CXCLB/IL-8, IFNγ, IL-1β, and TNFα. MHC II-low MSCs are the most appropriate type of allogeneic MSC to prevent activation of the innate and cell-mediated component of the adaptive immune systems and have increased gene expression as compared to other allogeneic MSCs.
© 2021. The Author(s).
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Publication Date: 2021-11-12 PubMed ID: 34772445PubMed Central: PMC8588742DOI: 10.1186/s13287-021-02624-yGoogle Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research studied the immune response of horses to the allogeneic administration of mesenchymal stromal cells (MSCs) it aims to understand the suitability of different types of MSCs in allogenic therapies. The research found that MSCs having low levels of major histocompatibility factor II (MHC II) are the most appropriate for preventing immune system activation and show increased gene expression compared to other MSC types.

Research Methodology

  • The bone marrow was harvested from Connemara, Standardbred, and Thoroughbred horses.
  • The MSCs obtained were grouped by their level of major histocompatibility factor II (MHC II) expression and those that derived from universal blood donor horses.
  • The MSCs were cultured in xenogen-free media for 48 hours and during all assays.
  • The cultivated MSCs underwent various tests, including co-culturing with responder leukocytes from a Connemara horse, interaction with complement, and haplotyping of their equine leukocyte antigen (ELA).

Findings

  • All allogeneic MSCs were found to be ELA mismatched with the responder leukocytes.
  • MHC II-low and universal blood donor MSCs did not cause peripheral blood mononuclear cell (PBMC) proliferation, increase in B cells, or activation of CD8 lymphocytes.
  • Universal blood donor MSCs stimulated a significant increase in the number of T regulatory cells.
  • Neutrophil interaction with MSCs showed that universal blood donor and MHC II-high allogenic MSCs caused more neutrophil activation than the other co-culture groups.
  • The presence of complement did not consistently cause MSC death.
  • Gene expression assays showed upregulated genes in universal blood donor and MHC II-low MSCs when cultured with allogenic lymphocytes compared to other co-cultures.

Conclusion

  • MHC II-low MSCs are most suitable for allogenic administration to prevent activation of innate and cell-mediated components of adaptive immune systems.
  • These types of MSCs also show increased gene expression compared to other allogenic MSCs, suggesting better integration with the host immune system.

This research adds valuable contribution to the field, providing insights on properties of different types of MSCs when used in allogenic transplantation and thus improving therapeutic potential for different conditions.

Cite This Article

APA
Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW. (2021). Immune response to allogeneic equine mesenchymal stromal cells. Stem Cell Res Ther, 12(1), 570. https://doi.org/10.1186/s13287-021-02624-y

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 12
Issue: 1
Pages: 570
PII: 570

Researcher Affiliations

Kamm, J Lacy
  • School of Veterinary Science, Massey University, Tennent Drive, Palmerston North, 4442, New Zealand. lacykamm@gmail.com.
Riley, Christopher B
  • School of Veterinary Science, Massey University, Tennent Drive, Palmerston North, 4442, New Zealand.
Parlane, Natalie A
  • AgResearch, Hopkirk Research Institute, Massey University, Palmerston North, 4474, New Zealand.
Gee, Erica K
  • School of Veterinary Science, Massey University, Tennent Drive, Palmerston North, 4442, New Zealand.
McIlwraith, C Wayne
  • School of Veterinary Science, Massey University, Tennent Drive, Palmerston North, 4442, New Zealand.
  • C. Wayne McIlwraith Translational Medicine Institute and the Orthopaedic Research Center, Colorado State University, 1678 Campus Delivery, Fort Collins, CO, 80523-1678, USA.

MeSH Terms

  • Animals
  • Bone Marrow Cells
  • Cells, Cultured
  • Hematopoietic Stem Cell Transplantation
  • Horses
  • Immunity
  • Leukocytes, Mononuclear
  • Mesenchymal Stem Cells / metabolism

Conflict of Interest Statement

J. Lacy Kamm and C. Wayne McIlwraith are directors in Advanced Regenerative Therapies—NZ. There are no competing interests for the other authors.

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Citations

This article has been cited 6 times.
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