Inferior In Vivo Osteogenesis and Superior Angiogeneis of Human Adipose-Derived Stem Cells Compared with Bone Marrow-Derived Stem Cells Cultured in Xeno-Free Conditions

Abstract

The possibility of using adipose tissue‐derived stromal cells (ATSC) as alternatives to bone marrow‐derived stromal cells (BMSC) for bone repair has garnered interest due to the accessibility, high cell yield, and rapid in vitro expansion of ATSC. For clinical relevance, their bone forming potential in comparison to BMSC must be proven. Distinct differences between ATSC and BMSC have been observed in vitro and comparison of osteogenic potential in vivo is not clear to date. The aim of the current study was to compare the osteogenesis of human xenofree‐expanded ATSC and BMSC in vitro and in an ectopic nude mouse model of bone formation. Human MSC were implanted with biphasic calcium phosphate biomaterials in subcutis pockets for 8 weeks. Implant groups were: BMSC, ATSC, BMSC and ATSC mixed together in different ratios, as well as MSC primed with either osteogenic supplements (250 μM ascorbic acid, 10 mM β‐glycerolphosphate, and 10 nM dexamethasone) or 50 ng/ml recombinant bone morphogenetic protein 4 prior to implantation. In vitro results show osteogenic gene expression and differentiation potentials of ATSC. Despite this, ATSC failed to form ectopic bone in vivo, in stark contrast to BMSC, although osteogenic priming did impart minor osteogenesis to ATSC. Neovascularization was enhanced by ATSC compared with BMSC; however, less ATSC engrafted into the implant compared with BMSC. Therefore, in the content of bone regeneration, the advantages of ATSC over BMSC including enhanced angiogenesis, may be negated by their lack of osteogenesis and prerequisite for osteogenic differentiation prior to transplantation. Stem Cells Translational Medicine 2017;6:2160–2172

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…Similar to what has been reported in regard to the effectiveness of MSCs, with some tissue sources preferable for certain indications (e.g., umbilical cord MSCs for immunomodulatory tasks [ 33 ] and BMSCs for bone regeneration [ 2 ] ), the tissue of origin also impacts the effectiveness of the MSC secretome. First, there is a significant difference in the levels of soluble factors and EVs secreted by MSCs according to their tissue of origin [ 124,242 ] and MSCs secrete EVs enriched in distinct miRNA and tRNA species [ 243 ] and proteins [ 242 ] according to their tissue of origin.…”

“…Mesenchymal stem/stromal cells (MSCs) are major cell candidates in regenerative medicine. MSCs can be isolated from diverse tissues in the body including the bone marrow, [ 1 ] adipose tissue, [ 2 ] umbilical cord, [ 3,4 ] placenta, [ 5 ] and dental pulp [ 6 ] ( Figure ). Some evidence indicates that MSCs in these tissues have a perivascular origin.…”

Mesenchymal stem cells: Cell therapy and regeneration potential

“…AT‐MSCs also differ in their differentiation potential when compared with BM‐MSCs. AT‐MSCs were able to differentiate towards the osteogenic lineage but not to the same extent as BM‐MSCs (Brennan et al, ; Im et al, ). However, in another study, there was no significant difference in the osteogenic potential of MSCs derived from BM and AT (De Ugarte et al, ).…”

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

“…As previously discussed, abdominal adipose tissue represents a promising alternative to iliac bone marrow, since; (a) it is relatively less invasive to harvest, and (b) the average yield of MSC‐like cells are reportedly greater compared to bone marrow (Bajek et al., ; Qadan et al., ). However, previous studies have suggested a lower intrinsic osteogenic potential of ASCs versus BMSCs in vitro and in vivo (Brennan et al., ; Liao & Chen, ). Moreover, the in vivo bone‐forming potential of ASCs has been demonstrated only when pre‐cultured in the presence of additional osteogenic stimulating factors (Scherberich et al., ).…”