Precision Perinatal Secretomics: Umbilical Cord Mesenchymal Stem Cell-derived Secretome as a Cell-free Therapeutic Platform for Maternal–Fetal Interface Disorders – A Narrative Synthesis
Wiku Andonotopo, Muhammad Adrianes Bachnas, Wisnu Prabowo, Eric Edwin Yuliantara, Mochammad Besari Adi Pramono, Julian Dewantiningrum, Efendi Lukas, I. Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dovy Djanas, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Theresia Monica Rahardjo, Rizna Tyrani Rumanti, Roland Frederik Lengkey, Anita Deborah Anwar, Aryani Aziz, Nuswil Bernolian, Cut Meurah Yeni, Laksmana Adi Krista Nugraha, Wibisana Andika Krista Dharma, Waskita Ekamaheswara Kasumba Andanaputra
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BSTRACT
Background:
Cell-free regenerative approaches are increasingly considered in pregnancy, where safety margins are inherently narrow and therapeutic tolerance is limited. Among these, the umbilical cord mesenchymal stem cell (UC-MSC)-derived secretome has gained attention. Still, its role at the maternal–fetal interface is not entirely straightforward, as angiogenic balance, immune tolerance, and inflammatory signaling rarely operate in isolation and tend to shift with context.
Objective:
To examine and integrate current evidence on UC-MSC-derived secretome in maternal–fetal interface disorders, with the aim of developing a mechanistically informed and translationally relevant framework.
Methodology:
This narrative review was conducted using a structured and systematic literature search informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 principles to ensure transparency in study identification and selection. A total of 312 records were screened across major databases, of which 35 studies were included following full-text assessment. Given the heterogeneity in study design, experimental models, and secretome characterization, a qualitative narrative synthesis was undertaken, with selected studies presented in structured tables based on methodological clarity and relevance.
Results:
Across diverse models, UC-MSC-derived secretome demonstrated predominantly paracrine effects, including partial restoration of angiogenic signaling, modulation of inflammatory pathways, and influence on immune cell dynamics at the maternal–fetal interface. These effects, however, were not uniform. Variations appeared across disease states, gestational timing, and bioengineering conditions, suggesting that biological activity is context-dependent rather than fixed.
Conclusion:
Such variability may be functionally meaningful rather than limiting. The concept of precision perinatal secretomics is proposed, framing the secretome as a modifiable therapeutic platform that can be aligned with specific pathophysiological contexts. While clinical translation remains incomplete, this perspective offers a structured way to connect mechanistic insight with future application.