Abstract
BackgroundStem cell therapies represent a promising tool in regenerative medicine. Considering the drawbacks of direct stem cell injections (e.g. poor cell localisation), extracellular matrix-based biomaterials (e.g. scaffolds and tissue grafts), due to their compositional biofunctionality and cytocompatibility, are under investigation as potential stem cell carriers.MethodsThe present study assessed the potential of three commercially available extracellular matrix-based biomaterials [a collagen/glycosaminoglycan scaffold (Integra™ Matrix Wound Dressing), a decellularised porcine peritoneum (XenoMEM™) and a porcine urinary bladder (MatriStem™)] as human adipose-derived stem cell delivery vehicles.ResultsBoth tissue grafts induced significantly (p < 0.01) higher human adipose-derived stem cell proliferation in vitro over the collagen scaffold, especially when the cells were seeded on the basement membrane side. Human adipose-derived stem cell phenotype and trilineage differentiation potential was preserved in all biomaterials. In a splinted wound healing nude mouse model, in comparison to sham, biomaterials alone and cells alone groups, all biomaterials seeded with human adipose-derived stem cells showed a moderate improvement of wound closure, a significantly (p < 0.05) lower wound gap and scar index and a significantly (p < 0.05) higher proportion of mature collagen deposition and angiogenesis (the highest, p < 0.01, was observed for the cell loaded at the basement membrane XenoMEM™ group). All cell-loaded biomaterial groups retained more cells at the implantation side than the direct injection group, even though they were loaded with half of the cells than the cell injection group.ConclusionsThis study further advocates the use of extracellular matrix-based biomaterials (in particular porcine peritoneum) as human adipose-derived stem cell delivery vehicles.Graphical abstractComparative analysis of a collagen scaffold (Integra™ Matrix Wound Dressing) and two tissue grafts [decellularised porcine peritoneum (XenoMEM™) and porcine urinary bladder (MatriStem™)] as human adipose-derived stem cells carriers
Highlights
Stem cell therapies represent a promising tool in regenerative medicine
This study further advocates the use of extracellular matrix-based biomaterials as human adipose-derived stem cell delivery vehicles
Cytocompatibility analysis Qualitative cell morphology, proliferation (Supplementary Figure S1) and viability (Supplementary Figure S2) analyses revealed that Human adipose-derived stem cells (hADSCs) attached, spread and proliferated in higher rates on either side of both tissue grafts than on tissue culture plastic (TCP) and the IntegraTM scaffold
Summary
Considering the drawbacks of direct stem cell injections (e.g. poor cell localisation), extracellular matrix-based biomaterials (e.g. scaffolds and tissue grafts), due to their compositional biofunctionality and cytocompatibility, are under investigation as potential stem cell carriers. Stem cell-based therapies emerged as the pinnacle of regenerative medicine and as the most promising therapeutic solution to a broad spectrum of injuries and degenerative conditions. Despite the high prospects and considerable advances of stem cell-based therapies, many limitations still need to be addressed for their efficient use in clinic, including poor cell engraftment at the implantation side and the large number of cells required for therapeutic effect [2]. In the quest of the ideal stem cell biomaterial carrier, extracellular matrix (ECM)-based biomaterials (e.g. extracted collagen scaffolds and decellularised tissue grafts) are favoured due to their inherent cytocompatibility, low immunogenicity and tunable mechanical properties. The ideal tissue graft for soft tissue repair and regeneration remains elusive, considering their scattered clinical outcomes (e.g. PermacolTM in hernia repair [3, 4], CorMatrix® in paediatric cardiovascular surgery [5, 6] and Strattice® in breast reconstruction [7, 8] have shown both positive and negative results)
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