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

Abstract

BackgroundIntra-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.MethodsIntra-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.ResultsFollowing 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.ConclusionsRepeated intra-articular injection of allogeneic MSCs results in an adverse clinical response, suggesting there is immune recognition of allogeneic MSCs upon a second exposure.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0503-8) contains supplementary material, which is available to authorized users.

Allogeneic vs. autologous intra‐articular mesenchymal stem cell injection within normal horses: Clinical and cytological comparisons suggest safety

“…Our study did not identify any significant differences in the clinical, cytological or biomarker response of the metacarpophalangeal joint to intra‐articular injection of allogeneic vs. autologous BMDMSCs. Previous studies which administered treatments (allogeneic vs. autologous MSCs) into different joints or different cohorts of horses are in agreement with these results . In addition to cell counts and differential cytology results which have been previously reported, our study investigates a synovial inflammatory mediator (PGE 2 ) and an acute phase protein (CRP).…”

“…Likewise, multiple injections of allogeneic or autologous mesenchymal stem cells may result in a different cytological or clinical response as found by Joswig et al . .…”

Subconjunctival bone marrow‐derived mesenchymal stem cell therapy as a novel treatment alternative for equine immune‐mediated keratitis: A case series

“…It has been shown that equine BM‐MSCs maintain constitutive surface expression of major histocompatibility complex (MHC) class I with variable surface expression of MHC class II and that equine allogeneic donor BM‐MSCs that are MHC‐mismatched to the recipient can elicit recipient T‐cell response in vitro . Additionally, allogeneic donor equine MSCs are capable of producing antibody responses in vivo in MHC‐mismatched recipients and repeated intra‐articular equine allogeneic MSC injections have been shown to cause an adverse response and more pain when compared to autologous MSC injections . Nevertheless, allogeneic therapy has been used clinically in a variety of conditions in equine medicine with no long‐term adverse effects noted .…”

Retrospective analysis of local injection site adverse reactions associated with 230 allogenic administrations of bone marrow‐derived mesenchymal stem cells in 164 horses

“…Another report comparing autologous and allogenic BM‐MSC joint injections showed no significant difference after a single injection . However, after a second injection, joints receiving allogenic cells demonstrated significantly greater TNCCs than those injected with autologous cells.…”

“…However, after a second injection, joints receiving allogenic cells demonstrated significantly greater TNCCs than those injected with autologous cells. It is important to note, that BM‐MSCs from one donor horse assigned to the allogenic group were also found to be positive for MHC II .…”