SECRET: Exploring the therapeutic potential of perinatal cell SECRETomes
SECRET is a highly interdisciplinary and intersectoral Doctoral Network funded under Horizon Europe’s Marie Skłodowska-Curie Actions programme focused on advancing scientific and technological breakthroughs in the field of perinatal derivatives for regenerative medicine applications.
SECRET will shape the coming generation of scientists in a well-structured and comprehensive manner to propel cell-free therapeutics 2.0 into clinical practice, and, ultimately, benefit the broader community. As part of this initiative, 10 doctoral candidates (DCs) will receive training in the area of stem cell biology, paracrine signalling mechanisms, advanced drug delivery methods and pre-clinical models for regenerative medicine applications.
SECRET brings together 6 Beneficiaries and 5 Associated Partners among excellent academic (8) and non-academic (3) centres from 6 different EU countries, mastering complementary disciplines covering three main areas: stem cell and extracellular vesicle biology, tissue engineering and biocompatible materials, and innovative technologies.
The need
Secretome-based drugs have gained growing recognition as a promising and safer alternative to cell-based therapies due to several key advantages. Unlike cell-based approaches, which can involve complex regulatory hurdles, issues with engraftment, and potential immune rejection, secretome-based therapies focus on the bioactive molecules secreted by cells, such as growth factors, cytokines, and extracellular vesicles (EVs). These molecules can exert therapeutic effects by promoting tissue regeneration, modulating immune responses, and enhancing repair processes without the risks associated with direct cell transplantation. As a result, they are increasingly viewed as a valuable option for achieving the benefits of cell-based therapies while minimizing associated risks.
In this context, secretomes derived from perinatal cells offer additional advantages. Perinatal tissues and organs, such as placenta, umbilical cord, and amniotic fluid, are easily accessible as they are typically discarded after birth, making their collection non-invasive and abundant. Unlike other cell sources, such as embryonic stem cells, the use of perinatal cells does not raise significant ethical concerns, as no harm is done to the mother or child during the collection process.
Moreover, perinatal cells have a unique biological profile, characterized by their potent regenerative and immunomodulatory properties, making their secretome highly effective for therapeutic purposes. These cells are rich in bioactive molecules, such as growth factors, cytokines, and EVs, which can enhance tissue repair, reduce inflammation, and promote healing in various clinical applications.
Overall, perinatal cell-based secretomes combine ease of access, ethical acceptability, and potent therapeutic potential, making them an attractive option in the development of next-generation regenerative and immune-modulating treatments.
Nevertheless, the clinical translatability of perinatal cell-based secretomes encounters several significant challenges that must be addressed to fully unlock their potential. These challenges include the lack of: i) standardized procedures for isolation of perinatal cells and for preparation of the secretomes derived thereof, ii) standardized route and time of administration, and iii) comparative functional studies between the different cell sources and iv) between relevant pathological conditions.
Addressing these challenges is crucial for advancing the clinical application of perinatal cell-based secretomes, and doing so requires a highly specialized yet interdisciplinary approach. The complexity of these issues demands expertise from multiple scientific and medical fields, working in close collaboration to overcome the obstacles that hinder the widespread use of these therapies. Standardizing isolation and preparation procedures, optimizing administration routes and timing, and conducting thorough comparative studies will be key to ensuring that these therapies can be safely and effectively integrated into regenerative medicine practices.
The interdisciplinary nature of SECRET—integrating cell biology, molecular, proteomic, mathematical and pathobiology competences—will be key to overcoming the current barriers and bringing perinatal cell-based secretomes closer to clinical implementation.
The solution
Within the SECRET consortium, the 10 DCs will be actively engaged in identifying the most potent perinatal cell-derived secretomes or EVs with either anti-inflammatory or pro-regenerative properties. The secretomes or EVs may come from different types of perinatal cells, such as those derived from the placenta, umbilical cord, or amniotic fluid, each offering distinct bioactive molecules that could be harnessed for therapeutic use.
The DCs will focus on rigorously analyzing and comparing the therapeutic potential of these secretomes and EVs, aiming to discover the most effective for specific functions, such as reducing inflammation or promoting tissue regeneration. This approach will require an interdisciplinary skill set, combining expertise in cell biology, bioengineering, molecular biology, and pre-clinical research, as they work to characterize the complex molecular compositions of these secretomes and evaluate their effects in various disease models.
Once the most potent secretomes or EVs have been identified, the DCs will take an innovative step by developing treatment schedules that optimize the therapeutic efficacy of these products as well as their targeted delivery. Such a combined treatment strategy would allow for greater flexibility in addressing multiple pathologies, ensuring that the treatments are tailored to the specific needs of the disease or injury being targeted.
By creating these innovative, multifaceted treatment regimens, the DCs will contribute to broadening the therapeutic applicability of PC-based therapies across a range of medical conditions, from chronic inflammatory diseases to regenerative medicine applications. This will also have a significant cost-effective impact, as identifying the most potent and versatile secretome or EV product could reduce the need for more invasive or costly treatments. Ultimately, this work will aim to deliver high-quality, scalable therapies that are accessible to a broader segment of the population, thus benefiting the wider community both medically and economically.
Overview of perinatal tissues and organs and of their derivatives. Perinatal derivatives encompass birth-associated tissues obtained from term placenta and fetal annexes [including amniotic membrane, chorionic membrane, chorionic villi, umbilical cord (including Wharton’s jelly), basal plate (containing both maternal and fetal cells), and amniotic fluid], the cells isolated from them, and the factors secreted by these cells. Adapted from Silini et al., Front Bioeng Biotechnol., 2020