Pig adipose mesenchymal stem cells (AMSCs) could be proposed for the improvement of bone substitute. However, these xenogenic cells retain a galactosyl (Gal) epitope that elicits xenorejection. Our work aims to use Gal-Knock-Out (Gal-KO) pig AMSCs to associate cellular immunomodulation, humoral down-elicitation of Gal-KO cells and osteogenic capacity of AMSCs. Human and pig AMSCs were compared for proliferation/differentiation kinetics and bone neoformation in vivo. Humoral reaction against pig Gal+ vs. Gal-KO AMSCs and immunomodulation properties of Gal+ vs. Gal-KO AMSCs were assessed in vitro. Humoral/cellular reactions against Gal+ vs. Gal-KO osteogenic differentiated pig AMSC xenografts were assessed in an immunocompetent rodent model. Expansion/differentiation/bone neoformation was significantly improved with differentiated pig AMSCs compared with human cells. Based on immunohistochemistry and cell-based ELISA, Gal+ AMSCs had higher sensitivity to preformed/induced anti-pig antibodies than Gal-KO AMSCs. In vitro cellular immunomodulation was similar between Gal+ and Gal-KO AMSCs. In vivo, a significant reduction of anti-pig IgG was found at 1 month in rats implanted with Gal-KO AMSCs compared with those implanted with Gal+ AMSCs. Lymphocyte/macrophage infiltration of osteogenic differentiated pig AMSC xenografts was significantly lower at post-operative day (POD) 7 in recipients of Gal-KO vs. Gal+ pig cells. No significant difference was found at POD 28. The combination of the cellular immunomodulation with the Gal-KO phenotype of AMSCs can significantly improve the cellular engraftment of pig osteogenic cells by delaying xenorejection.
Galactosyl-knock-out engineered pig as a xenogenic donor source of adipose MSCs for bone regeneration / Schubert T;Poilvache H;Galli C;Gianello P;Dufrane D. - In: BIOMATERIALS. - ISSN 0142-9612. - STAMPA. - 34:(2013), pp. 3279-3289. [10.1016/j.biomaterials.2013.01.057]
Galactosyl-knock-out engineered pig as a xenogenic donor source of adipose MSCs for bone regeneration.
GALLI, CESARE;
2013
Abstract
Pig adipose mesenchymal stem cells (AMSCs) could be proposed for the improvement of bone substitute. However, these xenogenic cells retain a galactosyl (Gal) epitope that elicits xenorejection. Our work aims to use Gal-Knock-Out (Gal-KO) pig AMSCs to associate cellular immunomodulation, humoral down-elicitation of Gal-KO cells and osteogenic capacity of AMSCs. Human and pig AMSCs were compared for proliferation/differentiation kinetics and bone neoformation in vivo. Humoral reaction against pig Gal+ vs. Gal-KO AMSCs and immunomodulation properties of Gal+ vs. Gal-KO AMSCs were assessed in vitro. Humoral/cellular reactions against Gal+ vs. Gal-KO osteogenic differentiated pig AMSC xenografts were assessed in an immunocompetent rodent model. Expansion/differentiation/bone neoformation was significantly improved with differentiated pig AMSCs compared with human cells. Based on immunohistochemistry and cell-based ELISA, Gal+ AMSCs had higher sensitivity to preformed/induced anti-pig antibodies than Gal-KO AMSCs. In vitro cellular immunomodulation was similar between Gal+ and Gal-KO AMSCs. In vivo, a significant reduction of anti-pig IgG was found at 1 month in rats implanted with Gal-KO AMSCs compared with those implanted with Gal+ AMSCs. Lymphocyte/macrophage infiltration of osteogenic differentiated pig AMSC xenografts was significantly lower at post-operative day (POD) 7 in recipients of Gal-KO vs. Gal+ pig cells. No significant difference was found at POD 28. The combination of the cellular immunomodulation with the Gal-KO phenotype of AMSCs can significantly improve the cellular engraftment of pig osteogenic cells by delaying xenorejection.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
