Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

Abstract

Numerous clinical studies have shown a wide clinical potential of mesenchymal stromal cells (MSCs) application. However, recent experience has accumulated numerous reports of adverse events and side effects associated with MSCs therapy. Furthermore, the strategies and methods of MSCs therapy did not change significantly in recent decades despite the clinical impact and awareness of potential complications.An extended understanding of limitations could lead to a wider clinical implementation of safe cell therapies and avoid harmful approaches. Therefore, our objective was to summarize the possible negative effects observed during MSCs-based therapies. We were also aimed to discuss the risks caused by weaknesses in cell processing, including isolation, culturing, and storage. Cell processing and cell culture could dramatically influence cell population profile, change protein expression and cell differentiation paving the way for future negative effects. Long-term cell culture led to accumulation of chromosomal abnormalities.Overdosed antibiotics in culture media enhanced the risk of mycoplasma contamination. Clinical trials reported thromboembolism and fibrosis as the most common adverse events of MSCs therapy. Their delayed manifestation generally depends on the patient's individual phenotype and requires specific awareness during the clinical trials with obligatory inclusion in the patient' informed consents. Finally we prepared the safety checklist, recommended for clinical specialists before administration or planning of MSCs therapy.

Role of Mesenchymal Stem/Stromal Cells in Modulating Ischemia/Reperfusion Injury: Current State of the Art and Future Perspectives

“…In particular, in different preclinical human studies in which organs from deceased donors were not suitable for transplantation, it has been shown that MSCs were able to reduce IRI side effects in both lung and kidney in the setting of mechanical organ perfusion [ 60 , 61 , 66 , 67 ]. However, despite the safety of MSC treatment having been widely demonstrated for different diseases in numerous patients [ 250 ], several studies have also reported adverse events and side effects associated with MSC therapy [ 251 ]. For instance, the long-term cell culture of MSCs can lead to genetic abnormalities with consequent tumorigenic effects.…”

“…For instance, the long-term cell culture of MSCs can lead to genetic abnormalities with consequent tumorigenic effects. Moreover, different clinical trials reported fibrosis and thromboembolism as the most common adverse events of MSCs therapy [ 251 ]. All these problems may be avoided by exploiting the paracrine properties of MSCs.…”

Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ

“…Perhaps, with further development of technology, such methods can be used for intraoperative cell isolation. To be used for tissue engineering in situ, the developed methods should ensure the isolation of a sufficient number of cells in a short time, and also not adversely affect the properties of the cells for safety reasons [ 125 ]. Extremely promising methods for enhancement of cell adhesion on scaffolds are presented by a surface micro/nano-imprinted patternization and laser engraving of surfaces of the implant [ 52 , 126 ].…”

Mesenchymal Stromal Cells as a Driver of Inflammaging

“…A growing list of clinical trials accumulated numerous reports on adverse events and side effects of cell-based therapies caused by the proinflammatory profile of MSC-secretome [ 16 ]. Being presented in various tissues, MSCs are both regulators and actors of local regeneration and immunomodulation [ 17 ].…”