Abstract
Currently, there is an increasing focus on mesenchymal stromal cells (MSC) as therapeutic option in bone pathologies as well as in general regenerative medicine. Although human MSCs have been extensively characterized and standardized, ovine MSCs are poorly understood. This limitation hampers clinical progress, as sheep are an excellent large animal model for orthopedic studies. Our report describes a direct comparison of human and ovine MSCs from three corresponding sources under the same conditions. All MSCs presented solid growth behavior and potent immunomodulatory capacities. Additionally, we were able to identify common positive (CD29, CD44, CD73, CD90, CD105, CD166) and negative (CD14, CD34, CD45, HLA-DR) surface markers. Although both human and ovine MSCs showed strong osteogenic potential, direct comparison revealed a slower mineralization process in ovine MSCs. Regarding gene expression level, both human and ovine MSCs presented a comparable up-regulation of Runx2 and a trend toward down-regulation of Col1A during osteogenic differentiation. In summary, this side by side comparison defined phenotypic similarities and differences of human and ovine MSCs from three different sources, thereby contributing to a better characterization and standardization of ovine MSCs. The key findings shown in this report demonstrate the utility of ovine MSCs in preclinical studies for MSC-based therapies.
Highlights
The bone is under constant turnover and remodeling, which is a well-regulated biological process during development and fracture healing [1,2]
This staining resulted in clearly higher values for both toward osteogenic differentiationinduced hMSCs and oMSCs compared to the corresponding controls (Figure 5B, left and middle)
mesenchymal stromal cell (MSC) play a key role in processes important for health and disease [25]
Summary
The bone is under constant turnover and remodeling, which is a well-regulated biological process during development and fracture healing [1,2]. The efficiency of hard tissue regeneration depends on a balance of osteogenic cell groups, osteoinductive stimulants, and osteoconductive matrix [4] These biological resources, appear to be limited in bone grafts and in the surrounding diseased tissue. Mesenchymal stromal cell (MSC) therapies have become an area of interest as they provide a possible adjuvant for tissue regeneration Due to their osteogenic and chondrogenic potential, they are a promising cell population which offers new ways to regenerate bone [5]. The characterization of MSCs from sheep is mandatory to investigate the efficacy of cell therapies for bone regeneration and implant osseointegration before clinical use of human MSCs. despite the convenience of utilizing sheep as a large animal model for orthopedics and the recent advantages in using MSCs, the number of studies involving ovine (o)MSCs is still very low [20]. The current study aimed to compare hMSCs directly with oMSCs from three sources, under the same conditions, and to delineate their characteristics comparatively as set by ISCT
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