Extracellular Calcium Modulates Chondrogenic and Osteogenic Differentiation of Human Adipose-Derived Stem Cells: A Novel Approach for Osteochondral Tissue Engineering Using a Single Stem Cell Source

Abstract

We have previously shown that elevating extracellular calcium from a concentration of 1.8 to 8 mM accelerates and increases human adipose-derived stem cell (hASC) osteogenic differentiation and cell-mediated calcium accretion, even in the absence of any other soluble osteogenic factors in the culture medium. However, the effects of elevated calcium on hASC chondrogenic differentiation have not been reported. The goal of this study was to determine the effects of varied calcium concentrations on chondrogenic differentiation of hASC. We hypothesized that exposure to elevated extracellular calcium (8 mM concentration) in a chondrogenic differentiation medium (CDM) would inhibit chondrogenesis of hASC when compared to basal calcium (1.8 mM concentration) controls. We further hypothesized that a full osteochondral construct could be engineered by controlling local release of calcium to induce site-specific chondrogenesis and osteogenesis using only hASC as the cell source. Human ASC was cultured as micromass pellets in CDM containing transforming growth factorb1 and bone morphogenetic protein 6 for 28 days at extracellular calcium concentrations of either 1.8 mM (basal) or 8 mM (elevated). Our findings indicated that elevated calcium induced osteogenesis and inhibited chondrogenesis in hASC. Based on these findings, stacked polylactic acid nanofibrous scaffolds containing either 0% or 20% tricalcium phosphate (TCP) nanoparticles were electrospun and tested for site-specific chondrogenesis and osteogenesis. Histological assays confirmed that human ASC differentiated locally to generate calcified tissue in layers containing 20% TCP, and cartilage in the layers with no TCP when cultured in CDM. This is the first study to report the effects of elevated calcium on chondrogenic differentiation of hASC, and to develop osteochondral nanofibrous scaffolds using a single cell source and controlled calcium release to induce site-specific differentiation. This approach holds great promise for osteochondral tissue engineering using a single cell source (hASC) and single scaffold.

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

“…These cells have been shown to exhibit the potential for osteogenesis, chondrogenesis, adipogenesis, myogenesis, as well as certain levels of neurogenesis in numerous studies (Erickson et al, 2002; Adams et al, 2012; Feng et al, 2014; Deshpande et al, 2015; Mellor et al, 2015). Despite the fact that ASCs show similarities to bone marrow MSCs, they exhibit a number of distinct characteristics, for example in their cell surface markers, differentiation potential, and abundance in the body.…”

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

“…Nowadays, a growing number of diseases can be improved via wide applications of stem cell transplantation, such as congenital cataract [12], diabetic retinopathy and keratopathy [13], myocardial infarction [14], ocular surface burns [15, 16], serious skin burns [17, 18], Parkinson's disease [19], Huntington's disease [20], and especially DFU [21]. Accumulating evidence has pointed out that mesenchymal stem cells (MSCs) may enhance wound healing [22–24] and be served as a cell source for many tissue engineering applications including bone regeneration [25], cartilage regeneration [26–28], myocardial regeneration [29], neurogenesis [30, 31], inflammatory bowel diseases [32], and DFU [33, 34]. MSCs exist in many tissues, for example, bone marrow [35, 36], umbilical cord [37, 38], placenta [39, 40], adipose tissue [36, 41–43], gingiva [44, 45], oral mucosa [46], amniotic fluid [47], and brain [48].…”

Adipose-derived human stem/stromal cells: comparative organ specific mitochondrial bioenergy profiles

“…Therefore, ASCs represent an attractive, abundant and readily available cell type for regenerative medicine. ASCs have been successfully used in tissue and wound regeneration such as sternal reconstruction (Khalpey et al 2015), cosmetic reconstruction (Koźlik and Wójcicki 2014), and chondrogenesis (Mellor et al 2015; Estes et al 2010). A major reason ASCs have shown great promise is that ASCs from the SVF have 50–74% of the matrix-forming ability of fibroblasts, which can be helpful in wound healing (Shin et al 2015).…”