Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases

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Abstract

Introduction

Various blood-derived products have been proposed for the topical treatment of ocular surface diseases. The aim of the study was to compare the different content of Growth Factors (GFs) and Interleukins (ILs) in peripheral blood (PB-S) and Cord Blood (CB-S) sera.

Materials and methods

Sera were obtained from 105 healthy adult donors (PB-S) and 107 umbilical/placental veins at the time of delivery (CB-S). The levels of epithelial-GF (EGF), fibroblast-GF (FGF), platelet-derived-GF (PDGF), insulin-GF (IGF), transforming-GF alpha (TGF-α,) and beta 1-2-3 (TGF-β1-β2-β3), vascular endothelial-GF (VEGF), nerve-GF (NGF), Interleukin (IL)-1β,IL-4,IL-6,IL-10, and IL-13 were assessed by Bio-Plex Protein Array System (Bio-Rad Laboratories, CA, USA). The Mann-Whitney test for unpaired data was applied to compare GFs and ILs levels in the two sources. The associations among each GF/IL level and the obstetric data for CB-S and hematological characteristics for PB-S were also investigated.

Results

The levels of EGF, TGF-α, TGF-β2, FGF, PDGF, VEGF, NGF, IL-1B, IL-4, IL-6, IL-10, and IL-13 were significantly higher in CB-S compared to PB-S. Conversely, the levels of IGF-1, IGF-2, and TGF-β1 were significantly higher in PB-S. The female sex and the weight of the child showed a significant association in predicting EGF and PDGF levels.

Conclusion

A significantly different content in those GFs and ILs was demonstrated in the two blood sources. Since each GF/IL selectively regulates different cellular processes involved in corneal healing, the use of PB-S or CB-S should be chosen on the basis of the cellular mechanism to be promoted in each clinical case.

Introduction

Blood derived products for the treatment of ocular surface diseases have been introduced some decades ago [1], and became increasingly popular in recent years [2]. Blood-derived products contain growth factors (GFs), cytokines, vitamins and nutrients present in natural tears, and aiming at promoting epithelial cell homeostasis, growth and migration. Therefore, the rationale for their use is to supply tears with these compounds.

Several different blood derivatives have been proposed for the treatment of various ocular surface disorders, in particular corneal wound healing (CWH) and dry eye disease (DED). Blood-derived products include eye drops prepared either from patients' own peripheral blood serum (autologous serum, AS) [[2], [3], [4]], platelet rich plasma [[5], [6], [7], [8]], plasma rich in GFs [5] and platelet lysate [9,10], or from donors, such as allogeneic umbilical cord blood serum (CB-S) [[11], [12], [13], [14], [15]] and allogeneic serum [16,17].

To date, no consensus has been reached about the methods of preparation, the quality control assessment, and the posology and duration of treatment [3,4,18].

In the absence of standardization, it is difficult to compare the levels of epitheliotrophic substances in the final products [19], as well as their therapeutic efficacy. In addition, only few prospective, randomized and controlled clinical trials comparing these products have been performed, and a recent Cochrane meta-analysis questioned the efficacy of autologous serum, the most popular among overall blood derived products [20].

The purpose of this work was to analyze and compare the content of a wide panel of epitheliotrophic growth factors and cytokines in PB-S from healthy donors versus CB-S, two allogeneic sources that can be utilized for the treatment of severe keratopathy.

Section snippets

Materials and methods

This is a prospective study on blood serum samples obtained from the Emilia Romagna Cord Blood Bank and from the Transfusional Service of the S.Orsola- Malpighi Teaching Hospital. The study was performed in respect to the principles in the Declaration of Helsinki. The study was approved by the local Ethical Committee (number of protocol 100/2016/O/Sper). Donors were requested to sign an informed consent after having been explained the scientific rationale of the study. Blood samples were

Characteristics of blood samples

A total of 107 CB samples was collected from spontaneous term births free of complications (≥ 37th week of pregnancy, n = 87) and Caesarean births (n = 20) The characteristics of mothers and babies are reported in Table 1a, divided by mother and baby donors.

A total of 105 PB samples was collected from adult healthy subjects, the donor characteristics are reported in Table 1b. All the CB-S and PB-S samples were analyzed as hereby described.

Growth factors and interleukin data

The growth factors and interleukins levels in CB-S and

Discussion

In this study, PB-S and CB-S were shown to contribute differently in terms of growth factors and interleukins content. As far as we know, this is the first study comparing a wide panel of growth factors and interleukins involved in CWH and DED. In fact, a few works compared CB-S and PB-S from healthy volunteer in the past literature. Yoon and co-workers showed that EGF and TGF-β concentrations were higher in CB-S compared to AS [23]. In another work, Shen et al. compared EGF, TGF-β1 and IGF-1

Conflicts ofinterset

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript.

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