A research team from the University of Trieste and Burlo Garofolo Research Hospital has developed an innovative strategy for preserving fertility in paediatric cancer patients. The strategy involves applying integrated bioengineering and cell therapy techniques to the autotransplantation of cryopreserved ovarian tissue. This procedure consists of extracting a portion of the ovary before cancer treatment, freezing it, and re-implanting it in the same patient once they have recovered.

In particular, the researchers demonstrated that adding autologous cells derived from blood vessels, isolated from the same sample, to the ovarian tissue can encourage faster revascularisation of the graft, thereby improving the supply of oxygen and nutrients. This approach could make a significant contribution to preserving fertility in affected patients.

The study is the result of collaboration with two major regional research institutions: the International Centre for Genetic Engineering and Biotechnology (ICGEB), under the guidance of Prof. Serena Zacchigna (head of the Cardiovascular Biology Laboratory and a lecturer at the University of Trieste), and the international research centre Elettra Sincrotrone Trieste.

The results of the study, conducted on animal models, were published in the prestigious scientific journal Bioactive Materials.

The research group is led by Chiara Agostinis, doctor and researcher at Burlo Garofolo Research Hospital; Roberta Bulla, lecturer at the Department of Life Sciences of the University of Trieste; and Giuseppe Ricci, lecturer at the Department of Medicine, Surgery and Health Sciences at the University of Trieste and Director of the Obstetrics and Gynaecology Clinic at Burlo Garofolo Research Hospital.

‘This work lays the groundwork for a follow-up preclinical study,’ explains Chiara Agostinis, ‘in which we plan to explore in more depth the potential and efficacy of our experimental approach, including its possible benefits for the endocrine function of the autotransplanted ovary.’

 ‘Although international guidelines have recently upgraded this procedure from experimental to clinical,’ adds Prof. Giuseppe Ricci, ‘several aspects of the protocol still need to be optimised; this would allow more hospitals and research institutes to adopt it as part of routine clinical care. At present, in Italy, very few centres offer this treatment, making access difficult for patients.’ 

The experimental protocol was developed by Dr Mariagiulia Spazzapan as part of her PhD research and represents a significant innovation in the field of fertility preservation. Dr Lorella Pascolo, a researcher at Burlo Garofolo Research Hospital, carried out post-transplant tissue assessment using X-ray microtomography. The analyses were conducted on the SYRMEP beamline at Elettra Sincrotrone Trieste by Dr Elena Longo.

Scientific research has made great strides in the treatment of paediatric cancers, which in most cases are now curable. However, the challenge remains to improve quality of life after treatment, which may involve chemotherapy or radiotherapy that can impair normal sexual development and fertility. 
In recent years, for prepubescent patients, autotransplantation of cryopreserved ovarian tissue has offered a tangible hope of fertility restoration. Nevertheless, this procedure still has a low success rate due to the lack of oxygen in the transplanted tissue before it becomes connected to the local blood supply. This condition causes stress that leads to the loss of many oocytes, drastically reducing the functionality of the transplanted tissue.

The success achieved by the research team in Trieste offers promising prospects for the development of new clinical solutions capable of giving young cancer patients a better long-term outlook for their health and fertility.

The study was funded by the Italian Ministry of Health (projects RC 23/18 and 20/23 Burlo Garofolo Research Hospital), the Ministry of University and Research (MUR), the National Recovery and Resilience Plan (NRRP) – Next Generation EU (CUP J53D23001020006 assigned to RB), and the PON Research and Innovation programme, REACT EU 2014–2020.

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Full study published in Bioactive Materials

Endothelial cell supplementation promotes xenograft revascularization during short-term ovarian tissue transplantation

Mariagiulia Spazzapana, Silvia Pegorarob, Roman Vuericha,c, Gabriella Zitob, Andrea Balduitb, Elena Longod, Lorella Pascolob, Miriam Toffolie, Giorgia Meshinie, Alessandro Mangognab, Gloria Rosf, Francesca Buonomob, Federico Romanob, Letizia Lombardellig, Giovanni Papae, Marie-Pierre Piccinnig, Serena Zacchignac,e, Chiara Agostinisb,*, Roberta Bullaa,1, Giuseppe Riccib,e,1.

1. Department of Life Sciences, University of Trieste, Trieste, Italy
2. Institute for Maternal and Child Health, Burlo Garofolo Research Hospital, Trieste, Italy
3. Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
4. Elettra Sincrotrone Trieste SCpA, Basovizza, Trieste, 34149, Italy
5. Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
6. Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT), Genova, Italy