Osteogenic Performance of Donor-Matched Human Adipose and Bone Marrow Mesenchymal Cells Under Dynamic Culture

Abstract

Adipose-derived mesenchymal cells (ACs) and bone marrow-derived mesenchymal cells (BMCs) have been widely used for bone regeneration and can be seeded on a variety of rigid scaffolds. However, to date, a direct comparison of mesenchymal cells (MC) harvested from different tissues from the same donor and cultured in identical osteogenic conditions has not been investigated. Indeed, it is unclear whether marrow-derived or fatderived MC possess intrinsic differences in bone-forming capabilities, since within-patient comparisons have not been previously done. This study aims at comparing ACs and BMCs from three donors ranging in age from neonatal to adult. Matched cells from each donor were studied in three distinct bioreactor settings, to determine the best method to create a viable osseous engineered construct. Human ACs and BMCs were isolated from each donor, cultured, and seeded on decellularized porcine bone (DCB) constructs. The constructs were then subjected to either static or dynamic (stirring or perfusion) bioreactor culture conditions for 7-21 days. Afterward, the constructs were analyzed for cell adhesion and distribution and osteogenic differentiation. ACs demonstrated higher seeding efficiency than BMCs. However, static and dynamic culture significantly increased BMCs proliferation more than ACs. In all conditions, BMCs demonstrated stronger osteogenic activity as compared with ACs, through higher alkaline phosphatase activity and gene expression for various bony markers. Conversely, ACs expressed more collagen I, which is a nonspecific matrix molecule in most connective tissues. Overall, dynamic bioreactor culture conditions enhanced osteogenic gene expression in both ACs and BMCs. Scaffolds seeded with BMCs in dynamic stirring culture conditions exhibit the greatest osteogenic proliferation and function in vitro, proving that marrow-derived MC have superior bone-forming potential as compared with adipose-derived cells.

Adipose Tissue-Derived Stem Cells in Regenerative Medicine

“…Comparative studies with ADSCs and bone marrow-derived MSC described minor differences regarding their differentiation potential and their immunomodulatory activity [16,17]. Thus, bone marrow-derived MSCs had a slightly better osteogenic capacity, but ADSCs show a more effective collagen production.…”

Comparative proteomic analysis of osteogenic differentiated human adipose tissue and bone marrow‐derived stromal cells

“…14,15 An intraindividual comparison of human MSCs of three donors cultured on decellularized porcine bone confirmed superior osteogenic capacity of BMSCs compared to ASCs. 16 On the other hand, a study by Rath et al found better osteogenic differentiation of ASCS compared to BMSCs using 3D bioglass scaffolds as a particular culturing condition. 17 Brennan et al isolated human BMSC from bone marrow aspirates and ASCs from lipoaspirates of healthy donors and characterized the cells based on surface markers and tri-lineage differentiation as outlined above.…”

Stemness specificity of epithelial cells – application of cell and tissue technology in regenerative medicine

“…Another positive aspect of ADSCs is that they are genetically and morphologically stable. Research data suggest that MSCs have a slight advantage where osteogenic capacity concerned [39]. On the other hand, ADSCs seem to be more efficient for collagen production [40].…”