Do ABO Blood Group Antigens Hamper the Therapeutic Efficacy of Mesenchymal Stromal Cells?

Abstract

Investigation into predictors for treatment outcome is essential to improve the clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We therefore studied the possible harmful impact of immunogenic ABO blood groups antigens – genetically governed antigenic determinants – at all given steps of MSC-therapy, from cell isolation and preparation for clinical use, to final recipient outcome.We found that clinical MSCs do not inherently express or upregulate ABO blood group antigens after inflammatory challenge or in vitro differentiation. Although antigen adsorption from standard culture supplements was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB plasma (ABP), dependent on antigen concentration and adsorption time. Compared to cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP elicited stronger blood responses after exposure to blood from healthy O donors in vitro, containing high titers of ABO antibodies. Clinical evaluation of hematopoietic stem cell transplant (HSCT) recipients found only very low titers of anti-A/B agglutination in these strongly immunocompromised patients at the time of MSC treatment. Patient analysis revealed a trend for lower clinical response in blood group O recipients treated with ABP-exposed MSC products, but not with HSA-exposed products.We conclude, that clinical grade MSCs are ABO-neutral, but the ABP used for washing and infusion of MSCs can contaminate the cells with immunogenic ABO substance and should therefore be substituted by non-immunogenic HSA, particularly when cells are given to immunocompentent individuals.

Characterization of Human AB Serum for Mesenchymal Stromal Cell Expansion

“…The human blood group AB is considered to be the most reasonable choice for serum production due to its lack of ABO antibodies, therefore avoiding harmful reactions [16,17]. Two plasma sources were evaluated for AB HS production: PC > 24 h and PCryoR.…”

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical Sciences Concerning Materials and Technologies Used for Medical and Dental Implantable Devices

“…Stem cells originating from bone marrow and fatty tissue may be used for breeding mesenchymal cells and tissues, in adipocytes, chondrocytes, osteoblasts and skeletal myocytes and can be used for producing tissues, e.g., muscles fat, gristle and bones [168][169][170][171]. Stringent safety requirements must be considered in cell-based therapies because raw materials of the animal origin are used, which poses a potential threat of transmitting a pathogen to a recipient or of immunological complications [172] and as post-production cleaning is required [173]. Progress in this domain seen since 2004 requires further detailed considerations concerning the mechanism of in vivo therapeutic activity, to facilitate the development and optimisation and for the development of automated processes, with improved efficiency and with quality control and with reference standards established [174][175][176][177].…”

Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population

“…The antigens of the ABO(H) system (A, B, and H determinants) consist of A carbohydrate structure and/or B carbohydrate structure on the substrate H core structure  (Moll et al, 2014). Although these structures are traditionally regarded as red cell antigens, A and B carbohydrate structures are actually expressed on a variety of human tissues, including epithelium, sensory neurons, platelets and vascular endothelium (Eastlund, 1998).…”