Amniotic epithelial cells and released mediators in support of regenerative effects, oncological treatments, and immune acceptance in allogeneic settings

Title : Amniotic epithelial cells and released mediators in support of regenerative effects, oncological treatments, and immune acceptance in allogeneic settings

Abstract:

The placenta is a non-controversial and readily available source of cells for regenerative medicine. The epithelial cells isolated from full-term amnion membrane contain several properties qualifying such cells as multipotent stem cells, with pluripotent characteristics and immunomodulatory capacities. Human Amnion Epithelial Cells (AEC) have been reported to engraft and reverse congenital disorders, boosting the innate capacity of regeneration and reversing inflammation and fibrosis in several organs. In addition to intact AEC, therapeutic potential is efficiently supported by the AEC secretome.

We profiled surfaceome in primary human AEC 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 AEC or secreted vesicles. Analysis of crago components and soluble mediators also qualifies these alternative medicinal products.

Immunomodulation and enhanced 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 damage.

Conclusions: Primary human AECs are characterized by immunological tolerance and long-term acceptance upon transplantation. Modulation and regenerative effects offered by intact AEC or secreted mediators may lead to new therapeutic interventions and enhanced regenerative effects in patients with acute or chronic disorders. Immune evasive capacity could be a “game changer”, and the modulation, rather than suppression, of innate and adaptive immune cells may result in enhanced cell treatments for regenerative purposes, autoimmune disorders, and tumors treated with augmented immune response

Biography:

Roberto Gramignoli has been working as a Senior Researcher and Group Leader at Karolinska Institutet, and recently appointed as Head of Division for Cell Therapies at Gaslini Hospital in Italy. He is specialized in Medical Genetics and advanced medicinal products, in addition to a PhD in Molecular and Translational Medicine. During his post-graduate studies at Univ. of Pittsburgh (PA-USA) he identified and proposed new solutions for roadblocks limiting clinical Hepatocyte Transplantation. Due to the paucity of human hepatocytes, he investigated alternative sources, such as iPS and placental stem cells. Working with his Mentor, Dr Strom, they became the first group to get approval for isolation and clinical infusion of human hepatocytes and amnion epithelial stem cells (AEC).

Over the past years, he has accumulated evidence on the potential of AEC in several models of congenital liver diseases and as supporting therapy in fulminant hepatic failure. Based on safety and efficacy, in addition to AEC immunomodulatory and anti-inflammatory effects, they are in the process of starting a phase I/IIa clinical trial for liver disease and creating the first placenta stem cell bank.