Photodynamic treatment with mono-phenyl-tri-(N-methyl-4-pyridyl)-porphyrin for pathogen inactivation in cord blood stem cell products

• Published in: Transfusion (Philadelphia, Pa.) Vol. 48; no. 12; pp. 2629 - 2637
• Main Authors: Trannoy, Laurence L., Van Hensbergen, Yvette, Lagerberg, Johan W.M., Brand, Anneke
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.12.2008; Wiley
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antigens, CD34 - immunology; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Differentiation; Cell Line, Tumor; Cell Survival; Female; Fetal Blood - cytology; Fetal Blood - drug effects; Fetal Blood - radiation effects; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - radiation effects; Humans; Medical sciences; Megakaryocytes - immunology; Mice; Porphyrins - pharmacology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vesiculovirus - drug effects; Vesiculovirus - pathogenicity; Vesiculovirus - radiation effects; Blood product; Treatment; Transfusion; Inactivation; Stem cell
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/j.1537-2995.2008.01907.x

BACKGROUND: Hematopoietic stem cell transplants and culture of hematopoietic progenitor cells require pathogen‐free conditions. The application of a method of pathogen inactivation in red blood cells using photodynamic treatment (PDT) was investigated for the decontamination of cord blood stem cell (CBSC) products. STUDY DESIGN AND METHODS: CBSC products, spiked with Gram‐positive and Gram‐negative bacteria, were treated with PDT using mono‐phenyl‐tri‐(N‐methyl‐4‐pyridyl)‐porphyrin (Tri‐P(4)) and red light. After PDT, in vitro and in vivo evaluation of the CBSC functions were performed. RESULTS: PDT of CBSC products resulted in the inactivation of the bacteria, with Staphylococcus aureus being the most resistant. Complete decontamination was achieved when CBSC products were contaminated with low titers of bacteria. PDT had no effect on white blood cell viability, the ex vivo expansion potential of the progenitor cells, and their capacity to differentiate to various hematopoietic cell lineages. However, PDT reduced the engraftment of human CBSCs in NOD/SCID mice, particularly affecting the B‐cell lineage engraftment. CONCLUSION: Pathogen inactivation of CBSC with Tri‐P(4)‐mediated PDT is feasible at contamination level up to 10 to 20 colony‐forming units per mL and can be considered when ex vivo expansion culture is anticipated. However, this treatment is not recommended for transplantation purposes at this time. Further investigations may elucidate why engraftment is diminished.