Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration

Abstract

Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

“…In previous investigations, it has been found that the combination of stem cell transplantation with other therapeutic methods could affect the efficiency of stem cell transplantation [45-48]. On the other hand, BMSCs transplantation has been revealed as a promising strategy for ONFH treatment; however, only patients with medium-size lesions could benefit from its application [15, 16]. The findings of other studies suggested that the treatment with SC-79 (an Akt activator) and Vitamin K2 significantly improved the efficacy of osteogenesis in animals [17, 21].…”

“…Preclinical study suggested that bone healing after autologous BMSCs treatment for ONFH begins two weeks after the transplantation, and complete healing is achieved after nine weeks [15]. A five-year follow-up study revealed that the combination of implantation of autologous bone marrow cells and auto-iliac cancellous bone grafts generated comparable clinical results with those of head-preserving procedures in medium-sized lesions [16], indicating that BMSCs implantation is promising for ONFH treatment.…”

Properties of porcine adipose-derived stem cells and their applications in preclinical models

“…Pigs are some of the most attractive and relevant large animal models for preclinical studies since their size, anatomy, genomic organization, and physiology are very similar to humans. 7,9,36 In a porcine preclinical model, the autologous transplantation of pASCs avoids triggering an adverse immune response.…”

“…Pigs have been used to investigate innovative pASCs bone regeneration strategies. 36 The osteogenic differentiation of pASCs is a well-known process. 23,37,38 Several studies combined pASCs differentiated into osteocytes with various types of scaffold such as hydroxyapatite, 22 polycaprolactone, 39 or oligo (polyethylene glycol) fumarate (OPF) hydrogel 40 to repair osteochondral defects.…”

Novel standardized massive bone defect model in rats employing an internal eight‐hole stainless steel plate for bone tissue engineering

“…Previous studies in large animals have shown massive bone defects regenerate well after implantation of tissue‐engineering bone (TEB, Viateau, Guillemin, & Bousson, ). Although bone defect models are well established in large animals, their production costs are high and intensive nursing is required; additionally, a long time is required for sample processing, which limited the suitable methods for sample evaluation (Rubessa et al, ). Moreover, the precise cellular and molecular mechanisms of bone repair are difficult to dissect.…”