Human umbilical cord blood plasma (hUCBP) is composed of the liquid phase of blood and contains various cytokines, growth factors, and immune modulatory factors (such as IGF, G-CSF, GM-CSF, MCP-1, IL-6, IL-8) that are able to regulate immune cells and adult stem cells.1,2,3,4 hUCBP is isolated using sterile technique during the harvesting of cord blood stem cells (a process that involves the centrifugation of cord blood) and contains plasticity promoting proteins that may have anti-aging effects that increase neurogenesis and cognitive function.5 Specifically, hUCBP is enriched with tissue inhibitor of metalloproteinases 2 (TIMP2), a factor that may increase synaptic plasticity and hippocampal function by regenerating brain cells lost in the aging process.6 Metalloproteinases (MMP), which TIMP2 targets, degrade extracellular matrixes and are known to increase during various pathological conditions including inflammatory diseases, tumor growth and metastasis.7
Animal models of acute ischemic stroke suggest that hUCBP enhances neurogenesis or the suppression of inflammation that contributes to enhanced recovery.1 These effects may be due to the activation of otherwise quiescent neural stem cells in the subventricular zone (SVZ). In addition hUCBP may be able to modulate T cells ability to produce and respond to IL-2 .2 hUCBP has also been shown in vitro to modulate CD69 expression.8 There may be evidence that T cells and IL-2 are involved in ischemic brain injury.9
Returning to the growth factors present, hUCBP has high concentrations of growth factors. For example, TGFβ is a growth factor associated with stem cell differentiation and is present up to 5-fold concentration higher than MSC 48 hour cultured media.3 Other growth factors present in high concentrations include EGF, FGF, NGF, VEGF, and PDGF.3
- Yoo, J., Kim, H. S., Seo, J. J., Eom, J. H., Choi, S. M., Park, S., … & Hwang, D. Y. (2016). Therapeutic effects of umbilical cord blood plasma in a rat model of acute ischemic stroke. Oncotarget, 7(48), 79131
- Bogunia-Kubik, K., Natarajan, P., Brown, S., Wolley, J., Alcocer, M., Fallen, P. R., … & Cohen, S. B. (2003). Cord blood serum affects T cells ability to produce and respond to IL-2. Cytokine, 22(1), 42-49.
- Pereira, T., Ivanova, G., Caseiro, A. R., Barbosa, P., Bártolo, P. J., Santos, J. D., … & Maurício, A. C. (2014). MSCs conditioned media and umbilical cord blood plasma metabolomics and composition. PLoS One, 9(11), e113769.
- Tekkatte, C., Gunasingh, G. P., Cherian, K. M., & Sankaranarayanan, K. (2011). “Humanized” stem cell culture techniques: the animal serum controversy. Stem cells international, 2011.
- Katsimpardi, L., Litterman, N. K., Schein, P. A., Miller, C. M., Loffredo, F. S., Wojtkiewicz, G. R., … & Rubin, L. L. (2014). Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science, 344(6184), 630-634.
- Castellano, J. M., Mosher, K. I., Abbey, R. J., McBride, A. A., James, M. L., Berdnik, D., … & Hinkson, I. V. (2017). Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature.
- Sorsa, T., Tjäderhane, L., & Salo, T. (2004). Matrix metalloproteinases (MMPs) in oral diseases. Oral diseases, 10(6), 311-318.
- Bogunia-Kubik, K., Natarajan, P., Madrigal, J. A., & Cohen, S. B. (2002). The effect of cord blood sera on CD69 expression. Immunology letters, 84(1), 77-80.
- Arumugam, T. V., Granger, D. N., & Mattson, M. P. (2005). Stroke and T-cells. Neuromolecular medicine, 7(3), 229-242.