Alloreactive Immune Response Associated to Human Mesenchymal Stromal Cells Treatment: A Systematic Review Sanabria de la Torre, Raquel Quiñones Vico, María Isabel Fernández González, Ana Sánchez Diaz, Manuel Montero Vílchez, Trinidad Sierra Sánchez, Álvaro Arias Santiago, Salvador Antonio Adverse events Alloantibodies Clinical trials Donor specific antibodies Immunogenicity Mesenchymal stromal cells Safety This research has received competitive funding in the call for grants for the financing of Research, Development and Innovation in Biomedicine and Health Sciences in Andalusia, for the year 2019 (PIGE-0247-2019; PIGE-0242-2019). 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. 2021-09-03T08:07:37Z 2021-09-03T08:07:37Z 2021-07-05 journal article Sanabria-de la Torre, R... [et al.]. Alloreactive Immune Response Associated to Human Mesenchymal Stromal Cells Treatment: A Systematic Review. J. Clin. Med. 2021, 10, 2991. [https://doi.org/10.3390/jcm10132991] http://hdl.handle.net/10481/70078 10.3390/jcm10132991 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI