Stem cell research & therapy2017; 8(1); 42; doi: 10.1186/s13287-017-0503-8

Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model.

Abstract: Intra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy. A direct comparison of the response of the synovial joint to intra-articular injection of autologous versus allogeneic MSCs has not been performed. The objective of this study was to assess the clinical response to repeated intra-articular injection of allogeneic versus autologous MSCs prepared in a way to minimize xeno-contaminants in a large animal model. Intra-articular injections of bone marrow-derived, culture-expanded MSCs to a forelimb metacarpophalangeal joint were performed at week 0 and week 4 (six autologous; six autologous with xeno-contamination; six allogeneic). In the week following each injection, clinical and synovial cytology evaluations were performed. Following the first intra-articular injection, there were no differences in clinical parameters over time. Following the second intra-articular injection, there was a significant adverse response of the joint to allogeneic MSCs and autologous MSCs with xeno-contamination with elevated synovial total nucleated cell counts. There was also significantly increased pain from joints injected with autologous MSCs with xeno-contamination. Repeated intra-articular injection of allogeneic MSCs results in an adverse clinical response, suggesting there is immune recognition of allogeneic MSCs upon a second exposure.
Publication Date: 2017-02-28 PubMed ID: 28241885PubMed Central: PMC5329965DOI: 10.1186/s13287-017-0503-8Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

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 investigates how repeated injections of foreign-originated, or allogenic, stem cells into joints can cause negative reactions, while injections of self-sourced, or autologous, stem cells do not provoke such reactions in an equine model.

Objectives and Methodology

  • The primary goal of the study was to compare the clinical response to repeated injections of allogenic and autologous Mesenchymal Stem Cells (MSCs) in a large animal model, focusing on osteoarthritis therapy.
  • The researchers derive the MSCs from bone marrow and then expand them within a cultured environment.
  • The joints of the subjects received injections of these MSCs at the start of the experiment and again after four weeks.
  • Three groups were used: one receiving autologous MSCs, the other autologous MSCs with contamination from foreign substances, and the last receiving allogenic MSCs.

Monitoring and Results

  • Clinical and synovial cytology evaluations, examining the fluid in their joint, were performed each week following injections, tracking specific clinical parameters over time.
  • The study found that following the first injection, there were no noticeable differences in these clinical parameters across all groups.
  • However, after the second injection, there was a significant negative response in the joints that received allogenic MSCs and autologous MSCs with contamination. Notably, there was a rise in total nucleated cell counts within the synovial fluid.
  • Also, there was a noticeable increase in pain perception in the group injected with contaminated autologous MSCs.

Significance of the Study and Findings

  • This study demonstrates for the first time how repeated intra-articular injection (directly into the joint) of allogenic MSCs may result in an adverse clinical response. This could imply that an immune recognition process occurs upon a second exposure to foreign-originating MSCs.
  • This result is significant in steering future study and clinical use of MSCs, particularly those of allogeneic and xeno-contaminated origins, in osteoarthritis therapy.

Cite This Article

APA
Joswig AJ, Mitchell A, Cummings KJ, Levine GJ, Gregory CA, Smith R, Watts AE. (2017). Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model. Stem Cell Res Ther, 8(1), 42. https://doi.org/10.1186/s13287-017-0503-8

Publication

ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 8
Issue: 1
Pages: 42
PII: 42

Researcher Affiliations

Joswig, Amanda-Jo
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Mitchell, Alexis
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Cummings, Kevin J
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
Levine, Gwendolyn J
  • Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA.
Gregory, Carl A
  • Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, Temple, TX, 76502, USA.
Smith, Roger
  • Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA.
Watts, Ashlee E
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA. awatts@cvm.tamu.edu.

MeSH Terms

  • Animals
  • Cattle
  • Female
  • Forelimb
  • Horses
  • Injections, Intra-Articular / adverse effects
  • Mesenchymal Stem Cell Transplantation / adverse effects
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology
  • Metacarpophalangeal Joint / immunology
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / adverse effects
  • Serum Albumin, Bovine / immunology
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • Transplantation, Autologous
  • Transplantation, Homologous / adverse effects

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