Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Abstract

Xenografting involves the transplantation of human tissue or cells into animal models and is an important tool for regenerative medicine research. Implantation of engineered human bone tissues into animal models, for example, is performed in preclinical evaluations of product safety and efficacy. With the advent of improved experimental methodologies, these models are further being exploited to interrogate molecular mechanisms and physiological interactions in vivo. In parallel to these developments, patient-derived xenograft murine models of cancer are increasingly being studied for various applications in cancer research and therapy; it follows that xenograft models in tissue engineering may be adapted for such approaches. In this review, we first discuss the development of human bone xenograft models to recapitulate physiological states in regenerative medicine. Subsequently, we discuss the use of these techniques for applications in modeling pathological states in skeletal oncology, namely, hematopoietic malignancies, bone metastatic disease, and primary bone malignancy.

Comparison of adipose stem cells sources from various locations of rat body for their application for seeding on polymer scaffolds

“…Preclinical models are largely restricted to rodents and are currently being assessed to improve host tolerance and the performance of biological transplants [5]; these include small animal species wherein tissue constructs are usually implanted ectopically and also for large animals, where they are usually implanted orthotopically [6]. The most commonly preferred animal model at an early stage is the rat (82%) [7] owing to its availability, abundance, small size, and ease of experimental manipulation. In orthopedic studies, rat models are used to examine femoral defects and skull defects (38-39%) and to a small extent, loss of tibia (3%) and mandibles (2%) [8][9][10][11].…”

“…In orthopedic studies, rat models are used to examine femoral defects and skull defects (38-39%) and to a small extent, loss of tibia (3%) and mandibles (2%) [8][9][10][11]. However, for comparison, the use of the porcine model represents an advantage in preclinical translation studies [7,12]. Such models are isomorphic with the clinical situation and yield accurately reproducible anatomical, physiological, and pathophysiological features in humans [13].…”

“…Such models are isomorphic with the clinical situation and yield accurately reproducible anatomical, physiological, and pathophysiological features in humans [13]. Thus far, none of the individual species has been identified as a standard preclinical animal model to assess regeneration in the human skeleton [7].…”

Prostaglandin EP4 Selective Agonist AKDS001 Enhances New Bone Formation by Minimodeling in a Rat Heterotopic Xenograft Model of Human Bone

“…The human bone xenograft model used in this study has the advantage of yielding homogeneous and stable human bone formation. The establishment of a stable human bone xenograft model is important because such a model could produce useful data in preclinical evaluations of medicines ( Chong et al, 2016 ). Several previous reports have evaluated human cell–derived bone formation through the combined use of cultured cells such as MSCs and artificial scaffolds ( Yoshikawa et al, 1996 ; Yoshikawa and Myoui, 2005 ; Wang et al, 2011 ; Liu et al, 2018 ).…”

Applied Induced Pluripotent Stem Cells in Combination With Biomaterials in Bone Tissue Engineering

“…Preferably, the bone of the patient's one's body (like the hip bone) is prepared as bone, says autologous bone. If someone else were prepared bone, allogeneic bone, and if something else is the origin of the species, the name of the bone xenograft [Chong et al, ].…”