title: Efficacy of homologous inositol hexaphosphate-loaded red blood cells in sickle transgenic mice.
abstract: Patients with sickle cell disease (SCD) can present several severe symptoms during their lifetime, including painful events due to vascular occlusion (VOC). Even though multiple factors are involved in VOC, hypoxia is the most important triggering factor. Inositol hexaphosphate (IHP) reduces the oxygen-haemoglobin affinity thus improving the oxygen release in the blood stream and in the tissues. Thus, IHP-loaded homologous red blood cells (IHP-RBCs) could be able to reduce disorders in SCD. The effectiveness of treatment was assessed in two types of SCD transgenic mice (BERK and SAD). The administration of four repeated injections of IHP-RBCs in BERK mice resulted in an improved survival rate and brain development, prevention of severe anaemia and a greatly lowered risk of VOC. After one injection of IHP-RBCs, SAD mice were subjected to acute hypoxic stress. Analysis of the lungs revealed significantly decreased mRNA levels of molecules involved in intravascular disorders. Our results showed that transfusion of homologous IHP-RBCs, by increasing the oxygen delivery, reduces SCD disorders in sickle transgenic mice.
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bourgeaux
authors.forename: Emeline
authors.initials: E
authors.lastname: Aufradet
authors.forename: Yannick
authors.initials: Y
authors.lastname: Campion
authors.forename: Geneviève
authors.initials: G
authors.lastname: De Souza
authors.forename: Françoise
authors.initials: F
authors.lastname: Horand
authors.forename: Amine
authors.initials: A
authors.lastname: Bessaad
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Chevrier
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Canet-Soulas
authors.forename: Yann
authors.initials: Y
authors.lastname: Godfrin
authors.forename: Cyril
authors.initials: C
authors.lastname: Martin
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000517:prevention & control; D001921:Brain / Q000254:growth & development / Q000473:pathology; D004195:Disease Models, Animal; D017707:Erythrocyte Transfusion / Q000009:adverse effects / Q000379:methods*; D005260:Female; D000860:Hypoxia / Q000209:etiology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size; D010833:Phytic Acid / Q000627:therapeutic use*; D012307:Risk Factors; D013154:Spleen / Q000254:growth & development / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D010833:Phytic Acid