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 The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
Summary
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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
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
- Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA.
- 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.
- Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA.
- 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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