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

Abstract

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are frequently used in the treatment of musculoskeletal injuries. Fully characterised cells that are readily available for use is optimum. Allogenic BM-MSCs can satisfy the need for rapid treatment, however, their safety has been questioned.

Objectives: Objectives were to characterise BM-MSCs from an adult donor horse, in vitro, and to identify and describe adverse reactions that occurred following their injection into other horses. We hypothesised that BM-MSCs capable of proliferation, differentiation and lacking MHC II from one donor could be implanted into another individual without significant adverse reactions and the frequency of adverse reactions in clinical cases would be similar to that previously reported for autologous BM-MSCs.

Study design: Retrospective clinical study.

Methods: BM-MSCs were proliferated and characterised from one donor and cryopreserved for clinical use. Medical records for horses injected with allogenic BM-MSCs from this donor at a single hospital were used. After routine lameness exam, lesions were identified using diagnostic ultrasound or MRI. Post injection reaction was defined as increased pain, swelling, or heat at or near injection site, or increased lameness. Treatments required for each reaction were noted.

Results: BM-MSCs proliferated and underwent differentiation. Cells were found to be negative for MHC-II (<2%) and were viable after cryopreservation and shipping. Ten of 230 (4.35%) injections were noted to be associated with an adverse reaction. Adverse reactions occurred in synovial structures (n = 3) and in soft tissues (n = 7).

Main limitations: This investigation could underestimate the number and severity of reactions. Mild reactions, such as synovitis, may have been missed. Also, anti-inflammatory drugs could overshadow mild reactions, making them less likely to be detected.

Conclusions: Fully characterised allogenic BM-MSCs originating from a single donor horse can be administered to horses with soft tissue injuries with a low rate of adverse reaction. The Summary is available in Portuguese - see Supporting Information.

Keywords: bone marrow; horse; musculoskeletal; regenerative; stem cell.