In the rapidly evolving field of regenerative medicine, the potential of umbilical cord blood (UCB) as a remarkable source of stem cells and other regenerative cellular components has garnered intense scientific interest. These cells possess the unique ability to differentiate and proliferate, offering hope for therapeutic interventions across a spectrum of diseases ranging from hematologic disorders to tissue repair. However, the methodologies employed for harvesting these precious cells play a pivotal role in determining both the quantity and quality of the collected cellular payload, thereby influencing downstream clinical outcomes.
A groundbreaking study published in Pediatric Research delves into comparing two prominent UCB collection techniques— the conventional needle-and-bag method and a manual cord milking approach. The investigation, conducted on samples from healthy term infants beyond 37 weeks gestation, sheds light on how different modes of blood extraction impact cell yield, viability, and stemness, critical parameters for regenerative applications. The significance of this work is underscored by the increasing clinical usage of UCB in cell therapy, where optimizing collection protocols could dramatically enhance therapeutic potency.
Traditionally, the needle-and-bag system has been the standard technique, wherein blood is drawn from the umbilical vein via a needle connected to a collection bag immediately after delivery. This method, while widely accepted and standardized, presents limitations such as variable blood volume retrieval, possible clotting, and time sensitivity. Conversely, manual cord milking involves physically squeezing the cord to push blood toward the collection point. It offers a dynamic alternative for rapid and potentially more volumetric harvest of blood cells but remains less characterized in terms of cell integrity and functional attributes.
This novel investigation extends the understanding of manual cord milking by examining two distinct applications: in utero milking performed while the placenta is still attached, and ex utero milking after the placenta has been delivered. The nuanced comparison between these techniques allows for a refined appreciation of how physiologic factors—such as placental attachment and oxygenation status—may influence harvested cell populations. The team’s meticulous approach incorporated collecting samples from term infants under controlled conditions, enabling comparable assessments across the methods.
Results revealed that manual cord milking, particularly when executed in utero, significantly enhanced the total nucleated cell count compared to the needle-and-bag collection. This finding is crucial, given that the number of nucleated cells often correlates with the therapeutic efficacy in regenerative treatments. Beyond the quantitative increase, the study also assessed cell viability, demonstrating that manual milking preserves cellular integrity effectively, dispelling concerns that mechanical manipulation might compromise cell health.
Further characterization of the collected cells using flow cytometry identified higher proportions of hematopoietic stem and progenitor cells—marked by CD34+ expression—in the in utero milking group. These stem cells are the cornerstone of many regenerative therapies, underscoring the clinical relevance of optimizing collection techniques. The ex utero milking group also showed improvements over the conventional method, although the yield was slightly lower than that observed in utero, suggesting placental physiology plays a role in cell mobilization.
An intriguing aspect of the research addressed the potential impact of these collection methods on endothelial progenitor cells (EPCs), which contribute to vascular regeneration. The manual milking technique again demonstrated superior recovery of EPCs, highlighting an additional therapeutic dimension beyond hematopoietic stem cells. This multifaceted cell retrieval enhances the translational potential of UCB in treating disorders involving vascular damage or ischemia.
The study also meticulously controlled for confounding variables such as gestational age, mode of delivery, and time elapsed between delivery and collection. This rigorous methodology strengthens the validity of findings, ensuring observed differences in cell yield and quality stem from the collection technique rather than extraneous factors. Additionally, the researchers conducted viability assays and functional colony-forming unit assays to verify that collected cells retained their proliferative capabilities, which are essential for successful engraftment and regeneration.
Moreover, the manual cord milking approach exhibited logistical and practical advantages—its swift execution potentially reduces the window for blood coagulation, thereby increasing usable volume. It also requires minimal additional equipment, making it an accessible technique in diverse clinical environments including resource-limited settings. Such operational benefits complement the biological enhancements, positioning manual cord milking as a promising standard practice for UCB collection.
Despite these compelling findings, the authors caution that larger-scale studies are needed to translate these results into clinical protocols fully. Variations in technique application, operator proficiency, and infant characteristics could influence outcomes in real-world settings. Additionally, the long-term functional impact of cells harvested via different methods on patient outcomes warrants comprehensive clinical trials.
This research contributes critical insights into optimizing cellular harvesting from umbilical cord blood, a key component for regenerative medicine’s future. By demonstrating that manual cord milking—especially when performed in utero—can significantly amplify and preserve valuable regenerative cell populations, the study challenges entrenched practices and paves the way for enhanced therapeutic cell sourcing.
As regenerative therapies continue to expand their reach across oncology, neurodegenerative diseases, and trauma recovery, ensuring robust, practical, and reproducible collection methods will be vital. The fusion of clinical pragmatism with cellular biology brute force demonstrated in this study exemplifies the type of innovation needed to catalyze next-generation regenerative interventions.
Ultimately, this work invigorates the scientific and medical communities to rethink umbilical cord blood procurement strategies, balancing technological sophistication with biomechanical ingenuity. Such advancements promise to substantially augment the supply and potency of regenerative cells, thereby broadening the horizon of curative therapies for countless patients worldwide.
The dialogue now turns to integrating these findings into clinical guidelines, training protocols, and biobanking standards. As evidence accumulates, manual cord milking could become a transformative maneuver—not just a simple mechanical technique but a cornerstone of regenerative medicine’s cellular supply chain. With mounting data supporting its efficacy, the momentum created by this study is likely to catalyze widespread adoption and further refinement of cord blood harvesting practices.
In essence, Marzan and colleagues’ investigation transcends a mere technical comparison, delivering a paradigm shift in how we envision and execute the collection of one of medicine’s most potent reservoirs of regenerative potential. The impact of these insights reaches beyond UCB itself, symbolizing a growing trend toward harmonizing clinical practice with cellular science to unlock therapeutic miracles hidden in birth’s aftermath.
As more research continues to unravel the biological nuances of cord blood cells obtained through different methodologies, this pioneering study sets a gold standard for future work. It reminds the scientific community that innovation often lies in revisiting and refining foundational techniques, turning routine procedures into revolutionary breakthroughs.
By placing the spotlight on the relatively underappreciated dynamics of placental attachment and milking timing, this work provokes fresh inquiries into the physiologic underpinnings governing stem cell mobilization. Such questions could spur novel technological developments, potentially leading to automated or optimized milking devices, further enhancing collection precision and repeatability.
With the relentless pursuit of regenerative therapies firmly on the global biomedical radar, this research instills optimism. It reaffirms that even well-trodden paths like umbilical cord blood harvesting can yield unexpected improvements with simple, thoughtful modifications. The future of regenerative medicine may well hinge on these incremental steps that magnify cell yield and quality, translating cellular bounty into tangible clinical benefits for ailing patients everywhere.
Subject of Research: Umbilical cord blood collection techniques; impact on cell yield and quality for regenerative therapies.
Article Title: Umbilical cord milking as a technique to harvest cord blood derived cells for regenerative applications.
Article References:
Marzan, R.A.S., Connelly, K., Razak, A. et al. Umbilical cord milking as a technique to harvest cord blood derived cells for regenerative applications. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04687-6
Image Credits: AI Generated
DOI: 27 December 2025
Tags: clinical usage of umbilical cord bloodcomparison of UCB collection methodsimpact of collection techniques on cell yieldneonatal stem cell researchoptimizing UCB collection protocolspediatric regenerative therapiesregenerative medicine advancementsstem cell collection methodstherapeutic applications of umbilical cord cellsumbilical cord blood harvesting techniquesumbilical cord milking procedureviability and stemness of stem cells
