Mouse models of multiple myeloma: technologic platforms and perspectives

Abstract

Murine models of human multiple myeloma (MM) are key tools for the study of disease biology as well as for investigation and selection of novel candidate therapeutics for clinical translation. In the last years, a variety of pre-clinical models have been generated to recapitulate a wide spectrum of biological features of MM. These systems range from spontaneous or transgenic models of murine MM, to subcutaneous or orthothopic xenografts of human MM cell lines in immune compromised animals, to platform allowing the engraftment of primary/bone marrow-dependent MM cells within a human bone marrow milieu to fully recapitulate human disease. Selecting the right model for specific pre-clinical research is essential for the successful completion of investigation. We here review recent and most known pre-clinical murine, transgenic and humanized models of MM, focusing on major advantages and/or weaknesses in the light of different research aims.

Keywords: SCID; SCID-hu; SCID-synth-hu; mouse models; multiple myeloma.

Figure 1. 5TMM and TG mouse models of MM

The pictures illustrate different strategies adopted to recapitulate MM disease. Models are divided according to their main characteristics: the green quadrant includes models of spontaneous mouse model of MM; the blue quadrant includes models of transgenic murine MM; each quadrant is accompanied by a table briefly describing the most relevant advantages and limits of each model. BD: bone disease; MM: multiple myeloma; BMM: bone marrow microenvironment

Figure 2. Xenograft and SCID models of MM

The pictures illustrate different strategies to recapitulate human MM disease in mice. The yellow quadrant includes models where human MM cells are grown in murine bone marrow microenvironment; the red quadrant includes models where human MM cells are grown in human autologous or allogenic bone marrow microenvironment; each quadrant is accompanied by a table briefly describing the most relevant advantages and limits of each model. BD: bone disease; MM: multiple myeloma; BMM: bone marrow microenvironment

Figure 3. Bone-disease model

The picture shows the radiologic evidence of a bone lytic lesion within a fetal bone chip. In the cartoon on the left, the main actors determining the bone resorption activity are reported. Th17: T helper 17 lymphocytes; MDSC: myeloid-derived suppressor cell; SC: stromal cell; OBL: osteoblast; MM: multiple myeloma cell; OCL: osteoclast.