Methods and criteria for validating the multimodal functions of perinatal derivatives when used in oncological and antimicrobial applications

Abstract

Perinatal derivatives or PnDs refer to tissues, cells and secretomes from perinatal, or birth-associated tissues. In the past 2 decades PnDs have been highly investigated for their multimodal mechanisms of action that have been exploited in various disease settings, including in different cancers and infections. Indeed, there is growing evidence that PnDs possess anticancer and antimicrobial activities, but an urgent issue that needs to be addressed is the reproducible evaluation of efficacy, both in vitro and in vivo. Herein we present the most commonly used functional assays for the assessment of antitumor and antimicrobial properties of PnDs, and we discuss their advantages and disadvantages in assessing the functionality. This review is part of a quadrinomial series on functional assays for the validation of PnDs spanning biological functions such as immunomodulation, anticancer and antimicrobial, wound healing, and regeneration.

Recommendations from the COST action CA17116 (SPRINT) for the standardization of perinatal derivative preparation and in vitro testing

“…The data of the PnD e-questionnaire show that the respondents had different priorities in this regard. However, our SPRINT COST Action has recently published a quadrinomial series of consensus reviews to improve the quality of in vitro testing linked to i) inflammation, angiogenesis and wound healing ( Flores et al, 2022 ), ii) oncological and antimicrobial applications ( Silini et al, 2022 ), iii) immunomodulatory functions ( Papait et al, 2022 ), and (iiii) PnD applications in brain, bone, skeletal muscle, heart, intestinal, liver, and lung pathologies ( Pozzobon et al, 2022 ). These publications not only provide researchers with guidance on which tests are appropriate, but also discuss advantages and disadvantages of assessing functionality.…”

“…Our SPRINT COST Action has recently published a series of consensus reviews on the relevance and potency of classical and new in vitro assays to demonstrate efficacy and potential MoA of PnD ( Flores et al, 2022 ; Papait et al, 2022 ; Pozzobon et al, 2022 ; Silini et al, 2022 ). Given the strong representation of PnD experts in the SPRINT COST Action, we now seek to address the issue of PnD definition and their characterization and provide a checklist of criteria that should be considered for any future study regarding PnD isolation, characterization and in vitro testing.…”

Human amniotic membrane inhibits migration and invasion of muscle-invasive bladder cancer urothelial cells by downregulating the FAK/PI3K/Akt/mTOR signalling pathway

“…In addition to extracellular macromolecules, such as collagens, laminins, proteoglycans and hyaluronic acid, hAM is a source of stem cells and various active signalling molecules, including interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), epidermal growth factor (EGF), interferon gamma (IFN-γ) and tissue inhibitor of metalloproteinases 1–4 (TIMP1-4) 13 – 15 . In recent years, a growing body of research has shown that the hAM has anticancer potential 16 – 21 . Namely, it has been shown that hAM preparations, hAEC and hAMSC as well as hAM scaffolds, inhibit the proliferation of muscle-invasive bladder cancer urothelial cells.…”

Mesenchymal Stromal Cells “Think” Globally, but Act Locally

“…MSCs are increasingly being used in clinical trials, e.g., for chronic graft-versus-host disease following haematopoietic stem cell transplantation [2]. Although the precise mechanism of action (MOA) of these cells in various clinical applications is not fully understood, recent progress has been made in the functional characterisation of MSCs and their extracellular vesicles, especially in the perinatal field [3][4][5][6], which can easily been translated to adult MSCs.…”