Generation of Human-to-Pig Chimerism to Induce Tolerance Through Transcutaneous In Utero Injection of Cord Blood-Derived Mononuclear Cells or Human Bone Marrow Mesenchymals Cells in a Preclinical Program of Liver Xenotransplantation: Preliminary Results

• Published in: Transplantation proceedings Vol. 44; no. 6; pp. 1574 - 1578
• Main Authors: Abellaneda, J.M, Ramis, G, Martínez-Alarcón, L, Majado, M.J, Quereda, J.J, Herrero-Medrano, J.M, Mendonça, L, García-Nicolás, O, Reus, M, Insausti, C, Ríos, A, López-Navas, A, González, M.R, Pallarés, F.J, Mun̄oz, A, Ramírez, P, Parrilla, P
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2012; Elsevier
• Subjects: Alu Elements; Animals; Animals, Newborn; Biological and medical sciences; Bone Marrow Transplantation - immunology; Cells, Cultured; Cord Blood Stem Cell Transplantation - adverse effects; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gestational Age; Guinea Pigs; Humans; Injections; Medical sciences; Mesenchymal Stem Cell Transplantation - adverse effects; Pregnancy; Real-Time Polymerase Chain Reaction; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Swine; Tissue, organ and graft immunology; Transplantation Chimera; Transplantation Tolerance; Transplantation, Heterologous; Ultrasonography, Interventional; Heterotransplantation; Blood; Percutaneous route; Mononuclear cell; Surgery; Bone marrow; Fetus; Graft; Ungulata; Human; Program; Digestive system; Tolerance; Mesenchymal cell; Injection; In utero; Pig; Vertebrata; Blood cell; Mammalia; Treatment; Animal; Artiodactyla; Chimerism; Umbilical cord
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2012.05.016

Abstract Objective Using a percutaneous ecoguided injection system to obtain chimeric piglets through a less invasive and traumatic technique than previously reported. Materials and methods The two types of human cells included umbilical cord blood mononuclear elements and mesenchymal stem cells cultured from bone marrow. Four sows at gestational day 50 were anesthetized. A needle was inserted through the skin and uterine wall to reach the peritoneal cavity of the fetuses under continuous ultrasound guidance. Fourteen piglets were injected with various cell concentrations. Results All sows carried pregnancies to term yielding 69 piglets, among which 67 were alive and two mummified. Two piglets died during the first 48 hours of life. Chimerism was detected using flow cytometry and by quantitative polymerase chain reaction (q-PCR) to detect Alu gene in blood or tissues samples. The analysis detected blood chimerism in 13 piglets (21%) by flow cytometry and the presence of the human Alu gene in 33 (51%) by q-PCR. The results suggest cell trafficking between littermates after in utero injection. Conclusions Transcutaneous echo-guided injection succeeded to produce chimeric piglets without disadvantages to the sow or the fetuses and avoiding abortions or fetal death.