Abstract
The well-known immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) are the reason why they are being used for the treatment of many diseases. Because they are considered hypoimmunogenic, MSCs treatments are performed without considering histocompatibility barriers and without anticipating possible immune rejections. However, recent preclinical studies describe the generation of alloantibodies and the immune rejection of MSCs. This has led to an increasing number of clinical trials evaluating the immunological profile of patients after treatment with MSCs. The objective of this systematic review was to evaluate the generation of donor specific antibodies (DSA) after allogeneic MSC (allo-MSC) therapy and the impact on safety or tolerability. Data from 555 patients were included in the systematic review, 356 were treated with allo-MSC and the rest were treated with placebo or control drugs. A mean of 11.51% of allo-MSC-treated patients developed DSA. Specifically, 14.95% of these patients developed DSA and 6.33% of them developed cPRA. Neither the production of DSA after treatment nor the presence of DSA at baseline (presensitization) were correlated with safety and/or tolerability of the treatment. The number of doses administrated and human leucocyte antigen (HLA) mismatches between donor and recipient did not affect the production of DSA. The safety of allo-MSC therapy has been proved in all the studies and the generation of alloantibodies might not have clinical relevance. However, there are very few studies in the area. More studies with adequate designs are needed to confirm these results.
Highlights
One study carried out cPRA measurement after allo-mesenchymal stromal cells (MSCs) administration in patients with degenerative disc disease (DDD) [50,51] and another study carried it out in patients with frailty syndrome (FS) [52]
Perin et al analyzed the activation of T-cells through mixed lymphocyte reactions (MLR) showing that MSCs did not elicit proliferative responses from patients’ cells [55]. Parameters such as the administration route, the tissue origin or the size of the MSC dose can influence the subsequent development of alloantibodies
IL administration route produced the greatest generation of alloantibodies
Summary
In 2006 the International Society for Cell and Gene Therapy (ISCT) set up minimal criteria defining mesenchymal stromal cells (MSCs). MSCs must be plastic-adherent when maintained in standard culture conditions. They must express CD73, CD90 and CD105 and lack expression of hematopoietic and endothelial markers CD11b, CD14, CD19, CD34, CD45, CD79alpha and HLA-DR. MSC must be capable of in vitro differentiation into adipocyte, chondrocyte and osteoblast lineages [1,2]
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