van Steenberghe M, Schubert T, Xhema D, Bouzin C, Guiot Y, et al.
The Journal of surgical research •
Glutaraldehyde-treated pericardia for cardiovascular applications have poor long-term clinical results. The efficacy of a combined physical/chemical treatment to improve pericardium biocompatibility and vascular regeneration was assessed and compared with detergent treatment and two commercial bovine pericardia: PeriGuard (DGBP) and Edwards pericardium (nDGBP). The physical and chemical process was applied to bovine and human pericardia (DBP-DHP), and the detergent process was applied to bovine (DDBP). Native (NBP) and treated bovine tissues were assessed for decellularization (HE/DAPI/DNA/α-Gal and MHC-1 staining) and mechanical integrity ex vivo. Twenty Wistar rats received subcutaneous patches of each bovine tissue to assess immunogenic response up to 4 months (flow cytometry). Ten additional rats received four subcutaneous bovine-treated patches (one/condition) to evaluate the inflammatory reaction (CD3/CD68 immunostaining), calcification (von Kossa staining/calcium quantification), and integration assessment (Hematoxylin and eosin staining). Finally, 15 rodents received a patch on the aorta (DBP n = 5, DHP n = 5, and DGBP n = 5), and vascular biocompatibility and arterial wall regeneration were assessed after 4 months (CD3/CD68/CD31/ASMA and Miller staining). DBP reached the higher level of decellularization, no immunogenic response whereas maintaining mechanical properties. DBP induced the lowest level grade of inflammation after 2 months (P < 0.05) concomitantly for better remodeling. No complications occurred with DBP and DHP where vascular regeneration was confirmed. Moreover, they induced a low level of CD3/CD68 infiltrations. This process significantly reduces immunogenicity and improves biocompatibility of bovine and human pericardia for better vascular regeneration.
Specenier PM, Remenar E, Buter J, Schrijvers DL, Bergamini C, et al.
Annals of oncology : official journal of the European Society for Medical Oncology •
Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy. Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.5 mg/ml/min. Primary endpoint was feasibility. Forty-seven patients were recruited. One patient did not start TPF (hypersensitivity reaction during the cetuximab loading dose). Induction TPF-E was discontinued in 12 patients due to toxicity (6 patients), medical decision (2), death (1), patient refusal (1), protocol violation (1), co-morbidity (1). Three further patients were not randomized [progressive disease (1), protocol violation (1), toxicity and co-morbidity (1)]. Of particular interest are three patients who suffered from bowel perforation, one patient who died as results of pneumonia and septic shock, and a second patient who was found dead at home 12 days after starting TPF-E (cause of death unknown). Weekly cisplatin and carboplatin was stopped early in seven and four patients, respectively. Radiotherapy was stopped in two patients with cisplatin and interrupted in one patient with cisplatin and four patients with carboplatin. The addition of cetuximab to full dose TPF induction chemotherapy led to unacceptable complications and premature closing of the study. Only 34 out of 46 patients completed four cycles of TPF-E and only 30 started biochemoradiation.
van Steenberghe M, Schubert T, Guiot Y, Bouzin C, Bollen X, et al.
Cell and tissue banking •
Glutaraldehyde preservation is the gold standard for cardiovascular biological prosthesis. However, secondary calcifications and the absence of tissue growth remain major limitations. Our study assessed in vitro and in vivo the biocompatibility of human (fascia lata, pericardium) and porcine tissues (pericardium, peritoneum) treated with a physicochemical procedure for decellularization and non-conventional pathogens inactivation. Biopsies were performed before and after treatment to assess decellularization (HE/Dapi staining/DNA quantification/MHC I/alpha gal immunostaining) and mechanical integrity. Forty-five rats received an abdominal aortic patch of native cryopreserved tissues (n = 20), treated tissues (n = 20) or glutaraldehyde-preserved bovine pericardium (GBP, control, n = 5). Grafts were explanted at 4 weeks and processed for HE/von Kossa staining and immunohistochemistries for lymphocytes (CD3)/macrophages (CD68) histomorphometry. 95% of decellularization was obtained for all tissues except for fascia lata (75%). Mechanical properties were slightly altered. In the in vivo model, a significant increase of CD3 and CD68 infiltrations was found in native and control implants in comparison with decellularized tissues (p < 0.05). Calcifications were found in 3 controls. Decellularized tissues were recolonized. GBP showed the most inflammatory response. This physicochemical treatment improves the biocompatibility of selected xeno/allogeneic tissues in comparison with their respective native cryopreserved tissues and with GBP. Incomplete decellularization is associated with a significantly higher inflammatory response. Our treatment is a promising tool in the field of tissue decellularization and tissue banking.
