Co-Transplantation of Fetal Bone Tissue Facilitates the Development and Reconstitution in Human B Cells in Humanized NOD/SCID/IL-2Rγnull (NSG) Mice

Abstract

In terms of the function and reconstitution efficacy of human immune cells, co-transplantation of human fetal tissues, such as thymus and liver, with CD34(+) hematopoietic stem cells (HSCs) has potential advantages in the generation of humanized mice. To examine the effects of bone tissues in the reconstitution of human immune cells, particularly in B cells, we generated a new humanized mice co-transplanted with human fetal thymus (hFT)/fetal bone (hFB) tissues and human fetal liver-derived CD34(+) cells. Humanized mice exhibited effective reconstitution of human immune cells earlier compared to control humanized mice. In terms of quantity, the number of immune cells, such as human T, B, and monocyte/macrophages was significantly increased. Furthermore, significant increase of B cell progenitors and immature/naïve B cells could be detected in the bone marrow and spleen of humanized mice. Our results demonstrate that co-transplantation of hFB tissue may facilitate the reconstitution of human B and T cells, and therefore the humanized model may be used to develop therapeutic human antibodies for clinical use.