Part of the neonatal population may present prematurity, birth asphyxia, chorioamnionitis, fetal growth restriction and congenital malformations at the time of birth . Although the advances of the last fifty years have improved their survival rate, there is still a strong need for specific interventions to reduce chronic morbidity and its effects on the lungs, heart or brain 2,3,4

Benefits of umbilical cord blood

Umbilical cord blood (UCB) has been used as a source of stem and progenitor cells since it was first used in 1988 5 for hematopoietic stem cell transplantation in a child with Fanconi anemia. Since then, it has been widely applied in the treatment of hematological malignancies and other conditions that require stem cell transplantation 6 .

Cord blood can be collected in large volumes, providing a mean of 81 ml in term newborns 7,8 , which means a nucleated cell count of 3.89-15.68 × 10 8 .

Even in premature infants, there is evidence that it can be collected in adequate volumes for therapy 9

The mononuclear fraction of cord blood contains a wide range of mature cells and progenitor stem cells that have a high capacity for differentiation 10,11,12 .

These populations include cells that have a variety of paracrine benefits , 14,15 such as hematopoietic stem cells, mesenchymal stromal cells, progenitor endothelial cells, T cells, or natural killer cells, among others.

Umbilical cord blood and tissue-derived cell therapy is attractive for preventive or regenerative treatment of neonatal morbidities

This is due to ease of access, low immunogenicity, or well-established collection and storage processes 16,17,7. It also plays in their favor that they can be collected in both vaginal deliveries and cesarean sections and that they can be used as autologous or allogeneic therapy.

The endorsement of clinical studies

As Lindsay Zhou et al . 18 indicate in their study , preclinical evidence supports the anti-inflammatory and regenerative effects of these cell therapies in the lungs, heart, and neonatal brain. This knowledge has been safely translated into 12 published clinical studies: 11 early phase trials and 1 phase II randomized controlled clinical trial.

The 12 trials involved 206 babies from around the world: 123 (60%) were full-term and 83 (40%) preterm.

A further 24 trials investigating cell therapies derived from blood and umbilical cord tissue in neonates are currently registered.

Outcomes in infants

The safety and feasibility of intravenous therapy with umbilical cord blood and tissue cells in term infants with hypoxic-ischemic encephalopathy (37 participants) and in premature infants with bronchopulmonary dysplasia (54 participants) has been established.

Likewise, the first signs of efficacy of mesenchymal cells from umbilical cord blood have been detected in extremely premature babies for bronchopulmonary dysplasia. Also in the case of MNC cells for infants with hypoxic-ischemic encephalopathy and hypoplastic left heart 18 .

Studies have been heterogeneous with respect to blood or tissue cell type, dose, and timing of administration.

Conclusions: safety and feasibility

This group of researchers concludes in their study that the clinical results to date demonstrate early safety and feasibility. This result is achieved using a variety of umbilical cord blood and tissue cell types, routes of administration, and disease targets.

Several of the currently registered trials attempt to assess dose-response and efficacy. A randomized controlled clinical trial has been published showing the early efficacy of human SCU MSC cell therapy for the treatment of bronchopulmonary dysplasia in extremely premature infants 19 .

With all this data, collaboration between cell therapy groups and those working in neonatal intensive care will be required. The objective is to establish multicenter randomized controlled clinical trials. Likewise, it is intended to continue testing the efficacy of cell therapies derived from blood and umbilical cord tissue in neonates.

References:

  1. Liu L, Oza S, Hagan D, et al. Global, regional, and national causes of under-5 mortality in 2000-2015: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388:3027-3035.
  2. Chow SSW, Creighton P, Kander V, Haslam R, Lui K. Report of the Australian and New Zealand Neonatal Network 2018. ANZNN; 2020.
  3. Perez A, Ritter S, Brotschi B, et al. Long-term neurodevelopmental outcome with hypoxic-ischemic encephalopathy. J Paediatr. 2013;163(2):454-459.
  4. Cheong J, Anderson P, Burnett A, et al. Changing neurodevelopment at 8 years in children born extremely preterm since the 1990s. Pediatrics. 2017;139(6).
  5. Gluckman E, Devergie A, et al. Transplantation of umbilical cord blood in Fanconi's anemia. Nouv Rev Fr Hematol. 1990;32(6):432-435.
  6. Ballen K. Umbilical cord blood transplantation: challenges and future directions. Stem Cells Transl Med. 2017;6(5):1312-1315.
  7. Ademokun J, Chapman C, Dunn J, et al. Umbilical cord blood collection and separation for haematopoietic progenitor cell banking. Bone Marrow Transplant. 1997;19:1023-1028.
  8. Reboredo NM, Diaz A, Castro A, Villaescusa RG. Collection, processing and cryopreservation of umbilical cord blood for unrelated transplantation. Bone Marrow Transplant. 2001;26:1263-1270.
  9. Segler A, Braun T, Fischer HS, et al. Feasibility of umbilical cord blood collection in neonates at risk of brain damage—a step toward autologous cell therapy for a high risk population. Cell Transplant. 2021;30:963689721992065.
  10. Broxmeyer HE. Biology of cord blood cells and future prospects of enhanced clinical benefit. Cytotherapy. 2005;7(3):209-218.
  11. Ali H, Bahbahani H. Umbilical cord blood stem cells—potential therapeutic tool for neural injuries and disorders. Acta Neurobiol Exp. 2010;70:316-324.
  12. Kogler G, Sensken S, Airey J, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med. 2004;200(2):123-135.
  13. Mcguckin P, Forraz N, Baradez M, et al. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolific. 2005;38:245-255.
  14. Castillo-Mendez M, Yawno T, Jenkin G, Miller S. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells. Front Neurosci. 2013;7:194.
  15. McDonald C, Penny T, Paton M, et al. Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following. perinatal hypoxic ischemic brain injury. J Neuroinflammation. 2018;15(47):1-14
  16. Couto P, Shatirishivili G, Bersenev A, Verter F. First decade of clinical trials and published studies with mesenchymal stromal cells from umbilical cord tissue. Regen Med. 2019;14(4):309-319.
  17. Secco M, Zucconi E, Vieira N, et al. Multipotent stem cells from umbilical cord: cord is richer than blood! Stem Cells. 2008;26(1):146-150.
  18. Lindsay Zhou, Courtney McDonald, et al. Umbilical Cord Blood and Cord Tissue-Derived Cell Therapies for Neonatal Morbidities: Current Status and Future Challenges. Stem Cells Translational Medicine, 2022, XX, 1–11.
  19. Anh SY, Chang YS, Lee MH, et al. Stem cells for bronchopulmonary dysplasia in preterm infants: a randomized controlled phase II trial. Stem Cells Transl Med. 2021;10(8):1129-1137
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