Human umbilical cord serum as an alternative to fetal bovine serum for in vitro expansion of umbilical cord mesenchymal stromal cells.

In the use of bovine fetal serum (FBS) there is concern about the possibility of disease transmission from animal to human. Therefore, it seems necessary to create culture conditions free of animal serum, especially in cell therapy. The aim of this study was to evaluate the feasibility of replacing human umbilical cord serum (hUCS) with FBS for in vitro expansion of umbilical cord mesenchymal stromal/stem cells (UC-MSCs). Here, UC-MSCs were cultured for five days in media supplemented either by hUCS or commercial FBS (Gibco and HyClone) to compare their viability, proliferation, morphology, Immunophenotype and differentiation potential. Our data shows that use of 5% and/or 10% hUCS, resulted in a tenfold increase in the number of MSCs; While in the presence of commercial FBS, this figure reached a maximum of five times. Notably, the rate of cell proliferation in the group containing 2% hUCS was the same as the groups containing 10% commercial FBS. Furthermore, there was no significant difference between groups in terms of viability, surface markers, and multilineage differentiation potential. These results demonstrated that hUCS can efficiently replace FBS for the routine culture of MSCs and can be used ideally in manufacturing process of UC-MSCs in cell therapy industry.

[Corneal regeneration: is there a place for tissues of perinatal origin?] / Regeneratsiya rogovitsy: est' li mesto dlya tkanei perinatal'nogo proiskhozhdeniya?

The article reviews the main properties of the cornea and the mechanisms of its physiological regeneration and repair in response to damage and describes the most promising methods of treatment aimed at stimulating limbal stem cells and based on the use of native tissues of perinatal origin, umbilical cord mesenchymal stromal cells, and cell-free therapeutic products.

Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

Treatment with human umbilical cord blood serum in a gentamicin-induced nephrotoxicity model in rats.

Sold under the brand name of Garamycin, gentamicin (GM) is an antibiotic in the category of aminoglycoside, that although does have many antibacterial properties, owing to several side effects, its consumption is confined. The current study is aimed at gauging the protective influences of human umbilical cord blood serum (hUCBS) on nephrotoxicity which is induced by GM. In this regard, in the present experimental design, twenty-eight male Wistar rats with the weights of 220 ± 20 g were categorized randomly into 4 groups of seven. The groups included GM (100 mg/kg), control as well as hUCBS at doses of one and two percent together with GM (100 mg/kg) for ten days in an intraperitoneal manner. Blood sampling was collected from the heart directly 24 h after the final injection for obtaining blood serum; the parameters of C-reactive protein (CRP), total oxidant status (TOS), interleukin (IL)-6, lactate dehydrogenase (LDH), total antioxidant capacity (TAC), creatinine (Cr), blood urea nitrogen (BUN), blood serum glutathione (GSH) were gauged in blood serum samples to evaluate renal function. Moreover, for histology, an examination of kidney tissue was performed. In comparison to those of the GM group, in the treatment group, hUCBS significantly decreased the levels of BUN, Cr, LDH, TOS, IL-6, and the CRP levels, and significantly increased the TAC and GSH levels. It was revealed that the treatment of the animals with hUCBS culminates in the reduction of GM' toxic impacts on the kidney.

Umbilical cord blood: Current uses for transfusion and regenerative medicine.

The past 20 years of experience with umbilical cord blood transplantation have demonstrated that cord blood is effective in the treatment of a spectrum of diseases, including hematological malignancies, bone marrow failure, hemoglobinopathies, and inborn errors of metabolism. However, only a few number of umbilical cord blood units collected have a cell content adequate for an allogenic hematopoietic stem cell transplantation. In the meanwhile, there is an increasing interest in exploiting cord blood derivatives in different fields. In this review, we will summarize the most recent updates on clinical applications of umbilical cord blood platelet derivatives for regenerative medicine, and we will revise the literature concerning the use of umbilical cord blood for autologous or allogeneic transfusion purposes. The methodological aspect and the biological characteristics of these products also will be discussed.

Human Umbilical Cord Blood Serum: Effective Substitute of Fetal Bovine Serum for Culturing of Human Multipotent Mesenchymal Stromal Cells.

Optimal conditions for culturing of multipotent mesenchymal stromal cells in the presence of pooled umbilical cord blood serum were determined. It was found that umbilical cord blood serum in a concentration range of 1-10% effectively supported high viability and proliferative activity of cells with unaltered phenotype and preserved multilineage differentiation capacity. The proposed approach allows avoiding the use of xenogenic animal sera for culturing of multipotent mesenchymal stromal cells and creates prerequisites for designing and manufacturing safe cellular and/or acellular products for medical purposes.

Feeder-free and xeno-free culture of human pluripotent stem cells using UCBS matrix.

The ideal medium for human pluripotent stem cells (hPSCs) culture should be feeder-free, xeno-free, and completely defined. The present study aims to establish a new feeder-free and xeno-free system for culturing hPSCs. The system consists of the matrix, which was prepared from human umbilical cord blood serum (UCBS) and used to coat the culture plates, and the xeno-free medium, which was conventional serum-free hES medium supplemented with high concentrations of bFGF and Fibronectin. Compared with matrigel and mouse embryonic fibroblasts (MEFs), the UCBS matrix was proved to be equally suitable for the growth of hPSCs. After a series of experiments with different media and cytokins, the UCBS matrix was found worked the best with the basic medium (BM) supplemented with 20 ng/mL bFGF, 10 ug/mL fibronectin and Y-27632 for culture of hES cells. The hPSCs maintained normal karyotype, high proliferation rate and self-renewal ability after continuous culture more than 10 passages in this feeder-free and xeno-free system. Furthermore, a new human embryonic stem (hES) cell line was derived from discarded day 3 embryos in this newly developed culture system. In conclusion, this feeder-free and xeno-free system could not only be used to the culture hPSCs, but could also be used to derive new hES cell lines.

Combined therapeutic use of umbilical cord blood serum and amniotic membrane in diabetic wounds.

Diabetic wounds are hard-to-heal due to complex multifactorial dysregulation within the micro-environment, necessitating the development of novel regenerative approaches to stimulate healing. This study investigated whether the combined therapeutic application of two novel cellular tissue products, namely a decellularized collagen-rich amniotic membrane (AmR) and growth factor-rich umbilical cord blood serum (UCBS) could have a positive synergistic effect on long-term healing outcomes by stimulating both superficial wound closure and wound bed regeneration. Full thickness excisional wounds were induced on obese diabetic mice (B6.Cg-lepob/J, ob/ob, n = 23) and treated with either: 1) Standard wound care (control); 2) UCBS; 3) AmR or 4) UCBS + AmR. Macroscopic wound closure was assessed on days 0, 3, 7, 10 and 14 post wounding. To determine the potential impact on wound recurrence, endpoint analysis was performed to determine both the overall quality of healing histologically as well as the molecular state of the wounds on day 14 via proteomic analysis. The data demonstrated the presence of both healers and non-healers. Re-epithelization took place in the healers of all treatment groups, but underlying tissue regeneration was far more pronounced following application of the combined treatment (UCBS + AmR), suggesting improved quality of healing and potentially a reduced change of recurrence long term. In non-healers, wounds failed to heal due to excessive slough formation and a reduction in LTB4 expression, suggesting impaired antimicrobial activity. Care should thus be taken since the cellular tissue product therapy could pose an increased risk for infection in some patients.

Therapeutic Profile of Human Umbilical Cord Blood Serum and Autologous Serum Therapies in Treatment of Ocular Surface Disorders: A Pilot Study.

Purpose: Umbilical cord blood serum (UCBS) is an effective adjunctive treatment along with conventional therapy in ocular surface disorders (OSDs). It aids in rapid ocular surface restoration thereby achieving epithelial integrity, in addition to improvement in subjective and objective parameters. The study aims to compare the efficacy of human umbilical cord blood serum and autologous serum (AS) in treatment of OSD. Methods: A prospective randomized study was conducted on 101 eyes diagnosed with OSD resulting from dry eye disease (DED; n = 40), acute chemical burn (ACB; n = 21), and ocular allergy (OA; n = 40). Randomization was done in Group I, administered with AS, and Group II with UCBS. Outcomes evaluated were visual acuity (VA), eye sensation score (ESS), ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer's value, Corneal Fluorescein Score, epithelial defect, limbal ischemia, corneal clarity (CC), and improvement in grade of severity. Statistical analysis was done using Wilcoxon signed-rank, Wilcoxon rank sum, Chi-square, and Z-test with a significance level (P ≤ 0.05). Results: In DED, Group II showed significant improvement in VA, ESS, and OSDI by the 7th day, whereas the mean Schirmer, TBUT, and corneal fluorescein staining score improved by 3 months. In ACB, Group II showed improvement in VA, reepithelialization, reduction in limbal ischemia, and CC by 3 months. In OA, Group II showed improvement in ESS by day 7. Conclusion: Human umbilical cord blood serum is more effective than AS in restoring ocular surface.

Association between telomere length in human umbilical cord tissues and polychlorinated biphenyls in maternal and cord serum.

Environmental exposure to persistent organic pollutants during pregnancy has potential adverse health effects on the fetus. One of the environmental pollutants is polychlorinated biphenyl (PCB). Earlier, we reported the presence of PCBs in fetal tissues such as the umbilical cord. Telomere length (TL) is a biomarker of aging because it shortens with each cell division. According to the Developmental Origins of Health and Disease hypothesis, fetal exposure to environmental pollutants during pregnancy affects the occurrence of non-communicable diseases in later life. In the current study, we investigated the association between cord tissue TL and serum levels of PCBs. The subjects were 114 mother-child pairs participating in a birth cohort study, the Chiba Study of Mother and Child Health (C-MACH). Maternal serum was collected during pregnancy, and cord serum and tissue were obtained at birth. TL was assessed by qPCR using genomic DNA extracted from the cord tissue. Maternal and cord serum PCB congener levels were assessed using gas chromatography and negative ion chemical ionization qMS. In male fetuses, serum levels of PCB74 in the cord blood were significantly associated with TL following covariate adjustment, but no significant association was found in female fetuses. These data suggest that the TL of the umbilical cord is affected by fetal exposure to PCBs.

Human umbilical cord blood serum attenuates gentamicin-induced liver toxicity by restoring peripheral oxidative damage and inflammation in rats.

Gentamicin (GM) is an aminoglycoside antibiotic that despite its antibacterial effects, its use is restricted due to numerous side effects. The umbilical cord serum contains various biomolecules that have protective impacts on the damaged tissues. The aim of this study was to gauge the protective effect of human umbilical cord blood serum (hUCBS) on GM-induced hepatotoxicity. In this experimental study, 28 male Wistar rats, weighing 220 ± 20 g, were randomly categorized into 4 groups including control, GM (100 mg/kg), hUCBS at doses of 1 and 2% along with GM (100 mg/kg) for 10 days, intraperitoneally. Twenty-four hours after the last injection, direct blood sampling was taken from the heart to obtain blood serum and liver enzymes, inflammatory cytokines and liver tissue were examined for histology. GM causes necrosis and inflammation in liver tissue. Liver enzyme and inflammatory cytokine levels were significantly increased in the GM group. Human umbilical cord blood serum significantly decreased liver enzyme and inflammatory cytokines levels in the experimental groups compared to the GM group. GM causes liver damage such as the inflammation and necrosis in liver tissue. Treating the animals with hUCBS reduced the toxic effects of GM in the liver.

Umbilical Cord Blood and Serum for the Treatment of Ocular Diseases: A Comprehensive Review.

Several blood derivatives have been proposed for the treatment of various ocular diseases that affect either the anterior or the posterior segment of the eye. Blood sources may range from the patient's own peripheral blood (autologous) to donor tissues, mainly allogeneic peripheral blood and umbilical cord blood (UCB). The utilization of the latter permits the collection of a large amount of serum all at once, and is characterized by therapeutic feasibility in patients with a poor general condition or anemia and blood dyscrasia. Products derived from UCB have two potential uses. First, serum in the form of eye drops can be applied topically onto the ocular surface to efficiently treat anterior segment disorders such as dry eye syndrome or corneal epithelial defects with different etiologies. The rationale for and efficacy of this application derive from the high concentrations of biologically active components and growth factors in UCB, which can nourish the ocular surface. Second, UCB is a source of stem cells, which are used in the field of regenerative medicine because they differentiate into various mature cells, including corneal and retinal cells. Therefore, UCB-derived stem cells have been proposed as a replacement therapy for the treatment of retinal and optic nerve diseases, given that current standard treatments often fail. The present review explores the clinical results that have been obtained using UCB-derived products in the field of ophthalmology, as well as the current limitations of those products in this field. Furthermore, given the promising development of UCB-based therapies, possible future directions in this area are discussed.