Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

Abstract

Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

Combination of resveratrol and 5‐azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells

“…Recent study has suggested that allogeneic stem cells may elicit an immune response in a recipient animal and that allogeneic donor MSCs are not fully immune-privileged, as previously claimed. 41 by controlling cytokine signalling and matrix remodelling, which was consistent with our results. Moreover, it was shown that DNAdemethylation was associated with the induction of the TET gene expression, which initiated the conversion of nuclear 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC).…”

Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis

“…It is plausible that an innate immune reaction to the ASCs and/or alloantibody production may have reduced ASC survival time and impeded their immunomodulatory effect which in turn also reduced the success rate and prolonged the clinical response . This is in agreement with previous studies that demonstrated that allogenic ASCs do not completely evade immune surveillance .…”

“…We were able to detect specific antibody development in one out of the five cats tested. This alloantibody formation in cats parallels and confirms what has been noted in many species including horses, pigs, macaques, rats and humans [38,41,[45][46][47][48][49]. Nonetheless, the significance of antibody development, in terms of clinical outcome, is hotly debated as many of these animals and humans show clinical improvement in spite of antibody development.…”

5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy

“…Increasing body of evidence suggests that allogeneic MSCs may elicit an immune response in a recipient animal and that allogeneic donor MSCs are not fully immune‐privileged, as previously claimed. The formation of anti‐allogeneic MSC antibodies, following an intradermal allogeneic MSC injection, was observed in horses . These results highlight the potential risk of allogeneic MSC application.…”