Biosafety Evaluation of Equine Umbilical Cord-Derived Mesenchymal Stromal Cells by Systematic Pathogen Screening in Peripheral Maternal Blood and Paired UC-MSCs.

The research paper is about biosafety concerns associated with the use of Mesenchymal Stromal Cells (MSCs) derived from equine umbilical cord, in particular the risk of pathogen contamination and the development of a standard protocol for microbiological safety assessment.

Introduction

• The study was driven by the increased interest in the use of Mesenchymal Stromal Cells (MSCs) particularly in equine medicine, and the potential risks associated with their use.
• MSCs are often sourced from the umbilical cord (UC) of horses (broodmares), but this particular source raises concerns due to the potential of environmental contamination and vertical transmission of pathogens from the mother horse.
• There is currently no scientific report of horses being infected through contaminated MSC products, but neither is there a consensus on a systematic screening procedure for pathogens in umbilical cord-derived mesenchymal stromal cells (UC-MSCs) to ensure the microbiological safety of these therapeutic products.

Objective and Methodology

• The researchers aimed to create a standard protocol that guarantees microbiological safety of UC-MSC and to evaluate the risk of vertical pathogen transmission from mother to offspring.
• They collected 84 samples from umbilical cords and paired peripheral maternal blood (PMB), the samples were collected between 2014 and 2016.
• The sterility of the samples was monitored with standard microbiological control tests and possible maternal contamination was examined by systematic PCR screening for 14 pathogens in PMB, along with a serological test known as the Coggins test.
• If a PMB sample was found to be PCR positive for one or more pathogens, the associated UC-MSCs were then analyzed using PCR for the detected pathogen(s).

Findings

• Out of 84 UC samples, 10 were contaminated upon extraction, and 6 remained positive in initial culture.
• For the rest of the UC and PMB sample pairs, they were evaluated for vertical transmission and 37 PMB samples were PCR positive for certain strains of Equidae herpes virus.
• However, when the paired UC-MSC samples were tested for the specific pathogens found in PMB, all of them returned negative results, suggesting a low inherent risk of vertical transmission.

Conclusions

• More research is needed to understand the susceptibility of MSCs to most pathogens detected in PMB.
• In-process microbiological controls combined with PMB PCR screening are an effective way to assess the risk of UC-MSC exposure to infectious viruses, especially given the inherently low risk of vertical transmission observed in the study.