Title : Cellular Mechanism in support of perinatal Amnion Epithelial Stem Cell Transplantation without Immunosuppression
Abstract:
The full-term placenta is a non-controversial and readily available source of stem cells for regenerative medicine. Our group was the first to isolate and validate regenerative effects offered by human amnion epithelial cells (hAEC), correcting congenital metabolic disorders. In all preclinical studies with immune-competent mice, hAEC engrafted and survived without the administration of immunosuppressive drugs. We proved safety and characterized multi-potent, immunomodulatory, and anti-inflammatory properties. We studied profiled surfaceome in primary hAEC and identified molecular pathways critical for immune-modulation and enhanced regenerative effects. We quantified the level of expression of non-polymorphic HLA-G and -E molecules, both as membrane-bound and soluble forms. Furthermore, purinergic mediators, hydrolyzed by classical and alternative nucleotidase pathways, reinforced immune-modulatory effects generated by intact hAEC or secreted vesicles. Immunomodulation and enhance immune response were measured on purified immune effector cells (T-, B-, NK-cells and macrophages), where the regulatory and anti-inflammatory switch was observed. Repair and supportive effects were validated in preclinical models of liver, kidney, and vocal fold damages. Conclusions: primary hAEC are characterized by immunological tolerance and long-term acceptance upon transplantation. Modulation and regenerative effects offered by intact hAEC or secreted mediators may lead to new therapeutic interventions and enhanced regenerative effects in patients with acute or chronic disorders. Based on their safety and the successful preclinical studies, approval was granted to begin banking of hAEC under GMP conditions at Karolinska Institutet, and to perform allogenic transplants on 10 patients without immunosuppression
