The Comparison of Immunomodulatory Properties of Canine and Human Wharton Jelly-Derived Mesenchymal Stromal Cells.

Although therapies based on mesenchymal stromal cells (MSCs) are being implemented in clinical settings, many aspects regarding these procedures require further optimization. Domestic dogs suffer from numerous immune-mediated diseases similar to those found in humans. This study aimed to assess the immunomodulatory activity of canine (c) Wharton jelly (WJ)-derived MSCs and refer them to human (h) MSCs isolated from the same tissue. Canine MSC(WJ)s appeared to be more prone to in vitro aging than their human counterparts. Both canine and human MSC(WJ)s significantly inhibited the activation as well as proliferation of CD4+ and CD8+ T cells. The treatment with IFNγ significantly upregulated indoleamine-2,3-dioxygenase 1 (IDO1) synthesis in human and canine MSC(WJ)s, and the addition of poly(I:C), TLR3 ligand, synergized this effect in cells from both species. Unstimulated human and canine MSC(WJ)s released TGFß at the same level (p > 0.05). IFNγ significantly increased the secretion of TGFß in cells from both species (p < 0.05); however, this response was significantly stronger in human cells than in canine cells. Although the properties of canine and human MSC(WJ)s differ in detail, cells from both species inhibit the proliferation of activated T cells to a very similar degree and respond to pro-inflammatory stimulation by enhancing their anti-inflammatory activity. These results suggest that testing MSC transplantation in naturally occurring immune-mediated diseases in dogs may have high translational value for human clinical trials.

Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial.

INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.

Premature fetal tissues are possible source of valuable mesenchymal stem cells.

OBJECTIVES: Comparison of the ability to inhibit alloactivated lymphocytes proliferation of human Wharton Jelly (WJ) and amniotic membrane (AM) mesenchymal stem cells (MSCs) from preterm and term pregnancies. MATERIAL AND METHODS: Term-WJ-MSCs (n = 5) and Preterm-WJ-MSCs (n = 1) were obtained from tissue explants by adherent method. Term-AM-MSCs (n = 5) and Preterm-AM-MSCs (n = 1) were obtained by tripsin and collagenase digestion method. Term and Preterm MSCs phenotype was confirmed in vitro by flow cytometry. To evaluate the potential of fetal and adult MSCs to diminish immunological response mixed lymphocytes reaction (MLR) has been performed. RESULTS: Term and Preterm cells were positively identified as MSCs by the expression of CD73 and CD90 and CD105 with simultaneous absence of CD11b, CD14, CD19, CD34, CD45 and HLA-DR. The mean inhibition of allostimulated lymphocytes after addition of fetal derived MSCs amounted 64.8% for term AM-MSCs and 42.1% for term WJ-MSCs (for both populations the effect was statistically significant, p < 0.01). The addition of preterm-MSCs to MLR resulted in reduction of stimulated lymphocytes proliferation by 64.9% for AM-MSCs and 86.1% for WJ-MSCs. CONCLUSIONS: Presented results suggest that preterm fetal tissues contain MSCs which posses similar immunosuppressive capacity as those from term pregnancies. In the future MSCs from the umbilical cord and amnion can be potentially used to prevent immuno-dependent injuries in premature newborns.