The umbilical cord, unlike other perinatal appendages such as cord blood or amniotic fluid, is invariably retained after birth and can be reliably collected even in emergency situations. Unlike the placenta, which comprises both maternal and fetal components, the umbilical cord exclusively reflects fetal characteristics. Moreover, it can be collected non-invasively, unlike blood sampling, making it an extremely valuable specimen for neonatal biobanking and research.
Umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) have garnered significant attention as somatic stem cells and are being extensively studied as a promising source for cell-based therapies in regenerative medicine. In addition to their multilineage differentiation potential, MSCs possess tissue repair capabilities through the secretion of various humoral factors such as HGF, BDNF, and bFGF. Furthermore, they exhibit immunomodulatory functions by secreting molecules such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), and HLA-G5, while lacking HLA-DR expression. These features—tissue regeneration and immune modulation—make MSCs particularly attractive therapeutic agents for pathological conditions involving tissue damage and inflammatory responses.
At the Institute of Medical Science, the University of Tokyo, we are conducting clinical research to develop UC-MSCs as regenerative medicine products. As of July 2025, there are 1,434 ongoing MSC clinical trials globally (compared to 371 in January 2022). Among these, 21 trials focus on neonatal and pediatric neurological conditions, with 9 specifically targeting cerebral palsy and HIE. The majority utilize UC-MSCs or adipose-derived MSCs. Other conditions under investigation include autism spectrum disorder, spinal cord injury, and neonatal stroke.
While UC-MSCs for therapeutic applications are typically derived from term infants, we have conducted proteomic analyses of umbilical cords derived from preterm infants for research purposes. The aim was to elucidate fetal developmental changes and characterize preterm-specific traits. Proteomic profiling of preterm umbilical cords revealed that proteins involved in immune responses, especially those mediating B cell function, were significantly upregulated with advancing gestational age, indicating progressive immune system maturation. In contrast, proteins related to mRNA processing, cytoplasmic translation, and ribonucleoprotein complex biogenesis showed inverse trends, suggesting elevated biosynthetic activity in extremely preterm neonates. Protein markers associated with organ development exhibited heterogeneous trajectories. These findings demonstrate that umbilical cord proteomics can serve as a powerful platform for assessing functional maturity at birth—particularly of the immune system—and may facilitate the discovery of biomarkers and therapeutic targets relevant to neonatal care.
In conclusion, the umbilical cord represents a highly valuable resource—not only as a source of UC-MSCs for regenerative medicine, but also as an insightful specimen for understanding the pathophysiology of prematurity.