Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells

Abstract

Since discovery, significant interest has been generated in the potential application of mesenchymal stem cells or multipotential stromal cells (MSC) for tissue regeneration and repair, due to their proliferative and multipotential capabilities. Although the sheep is often used as a large animal model for translating potential therapies for musculoskeletal injury and repair, the characteristics of MSC from ovine bone marrow have been inadequately described. Histological and gene expression studies have previously shown that ovine MSC share similar properties with human and rodents MSC, including their capacity for clonogenic growth and multiple stromal lineage differentiation. In the present study, ovine bone marrow derived MSCs positively express cell surface markers associated with MSC such as CD29, CD44 and CD166, and lacked expression of CD14, CD31 and CD45. Under serum-deprived conditions, proliferation of MSC occurred in response to EGF, PDGF, FGF-2, IGF-1 and most significantly TGF-alpha. While subcutaneous transplantation of ovine MSC in association with a ceramic HA/TCP carrier into immunocomprimised mice resulted in ectopic osteogenesis, adipogenesis and haematopoietic-support activity, transplantation of these cells within a gelatin sponge displayed partial chondrogenesis. The comprehensive characterisation of ovine MSC described herein provides important information for future translational studies involving ovine MSC.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…The multilineage differentiation ability, paracrine effects and immunomodulatory properties of MPCs make them an ideal for tissue engineering and regenerative purposes [5,7,[46][47][48]. Under appropriate conditions MPCs could be differentiated into a variety of mesenchymal tissues such as bone, cartilage, tendon, ligament, marrow stroma, muscle, fat and dermis [4,[49][50][51][52][53]. To induce fracture healing, MPCs are expanded ex vivo prior to their autologous grafting to the fracture site and differentiated into osteogenic lineages to promote bone regeneration [9,54].…”

“…The bone mineral density and bone strength in sheep is increased relative to human. Moreover, sheep models of critical size defects are extensively applied to evaluate cell-based therapeutic approaches using autologues, allogeneic or xenogeneic MPCs in combination with growth factors and different types of scaffolds to enhance bone regeneration showing significant advantages compared with cell-unloaded (empty) scaffolds [43,53,166,[169][170][171][172][173][174][175][176].…”

RECENT RESEARCH ON THE GROWTH PLATE: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration

“…In all of these models, bony repair and/or bone growth defects that mimic the human clinical outcomes can be demonstrated. In particular, in the last decade more extensive work using a rat proximal tibial drill hole model has been performed , Arasapam et al 2006, Chung et al 2006, 2013a,b, 2014, Ngo et al 2006, McCarty et al 2009, Macsai et al 2011, which has demonstrated different phases of injury repair that lead to the undesirable bony repair, namely the inflammatory, the fibrogenic, and the osteogenic and remodelling phases, on days 1-3, 4-8 and 8 onwards respectively (Fig. 2).…”

“…Adult MSCs are capable of differentiating into cells of many tissues such as cartilage, bone, and fat. In addition, MSCs can be isolated from many different sources, including the periosteum, trabecular bone, adipose tissue, synovium, skeletal muscle, as well as the bone marrow , McCarty et al 2009. Interestingly, previous studies have observed that synovium-derived MSCs in particular had the greatest capability to enhance the chondrogenic differentiation potential when compared with any other mesenchymal tissue-derived cells (Sakaguchi et al 2005).…”

“…In regard to growth plate cartilage repair, ideally, a combination of growth factors would firstly assist with optimal expansion of MSCs and then with the induction of chondrogenic differentiation. Some of the growth factors that have previously been studied for their MSC mitogenic properties include PDGF, IGF1, FGF2 and TGFa (McCarty et al 2009), and growth factors with known chondrogenic properties include FGF2, TGFB1, TGFB3, BMP7 and IGF1 (Lennon et al 1995, Yamaguchi 1995, Johnstone et al 1998, Worster et al 2000, McCarty et al 2009. FGF2 has been shown to have potent mitotic properties as well as encouraging MSCs differentiating towards a chondrogenic differentiation (Solchaga et al 2005).…”