Cord blood and amniotic membrane extract eye drop preparations display immune-suppressive and regenerative properties

• Published in: Scientific reports Vol. 11; no. 1; p. 13754
• Main Authors: Samarkanova, Dinara, Cox, Steven, Hernandez, Diana, Rodriguez, Luciano, Pérez, Maria Luisa, Madrigal, Alejandro, Vilarrodona, Anna, Querol, Sergio, Casaroli-Marano, Ricardo P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 692/308; Amnion - chemistry; Amniotic membrane; Animals; Bioavailability; Blood Platelets - immunology; Cell culture; Cell Proliferation - drug effects; Cord blood; Cornea; Cornea - drug effects; Cornea - growth & development; Corneal Diseases - drug therapy; Corneal Diseases - pathology; Cytokines; Epithelial cells; Epithelial Cells - drug effects; Eye; Eye disorders; Female; Fetal Blood - chemistry; Fetal Blood - immunology; Growth factors; Humanities and Social Sciences; Humans; Immunomodulation; Inflammation; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - pharmacology; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes T; multidisciplinary; Natural killer cells; Ophthalmic Solutions - chemistry; Ophthalmic Solutions - pharmacology; Placenta; Placenta - chemistry; Placenta - immunology; Pregnancy; Quality of Life; Regeneration - drug effects; Science; Science (multidisciplinary); Swine; Wound Healing; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-93150-7

Diseases and injuries that compromise the ocular surface cause considerable patient distress and have long term consequences for their quality of life. Treatment modalities that can address the delicate balance of tissue regeneration, inflammation and maintenance of corneal transparency are therefore needed. We have recently formulated two novel eye drops from placental tissues: cord blood platelet lysate (CBED) and amniotic membrane extract eye drops (AMED), which can be used to treat severe ocular disorders. Here we characterise these two preparations by measuring: (a) growth factors (GF) and cytokines composition, (b) promotion of human corneal epithelial cell (HCEC) growth and (c) effects on immune cells in a lymphocyte culture assay. Finally, their bioavailability was assayed in an ex vivo porcine corneal model. We show that both preparations contain GF and cytokines that were able to promote the in vitro growth of HCEC and support repair in an in vitro scratch test. When assessed in a lymphocyte culture, both favoured immune suppression reducing the cellular expression of NKG2D and CD107a as well as the production of interferon gamma (IFN-γ) in natural killer, NKT and T cells. Regarding bioavailability, CBED active molecules were found mainly in the pre-corneal fraction with some penetration into the corneal fraction, in an ex vivo model. In summary, both placental-derived allogeneic preparations, CBED and AMED, display regenerative and immunomodulatory capabilities. These results will help define mechanisms of action and the best indications and doses of each product for use in a particular patient and support the development of off-the-shelf therapies for ocular surface pathologies in which wound healing defects and inflammatory events are contributing factors.