In vivo comparison of biomineralized scaffold-directed osteogenic differentiation of human embryonic and mesenchymal stem cells

Abstract

Human pluripotent stem cells such as embryonic stem cells (hESCs) and multipotent stem cells like mesenchymal stem cells (hMSCs) hold great promise as potential cell sources for bone tissue regeneration. Comparing the in vivo osteogenesis of hESCs and hMSCs by biomaterial-based cues provides insight into the differentiation kinetics of these cells as well as their potential to contribute to bone tissue repair in vivo. Here, we compared in vivo osteogenic differentiation of hESCs and hMSCs within osteoinductive calcium phosphate (CaP)-bearing biomineralized scaffolds that recapitulate a bone-specific mineral microenvironment. Both hESCs and hMSCs underwent osteogenic differentiation responding to the biomaterial-based instructive cues. Furthermore, hMSCs underwent earlier in vivo osteogenesis compared to hESCs, but both stem cell types acquired a similar osteogenic maturation by 8 weeks of implantation.

Bone Morphogenetic Protein‐2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels

“…Cell-based approaches utilizing mesenchymal stem cells (MSCs) are under investigation for bone repair of atrophic nonunions, craniomaxillofacial defect repair, and hard palate reconstruction. [3] MSCs are multipotent cells that, among other phenotypes, can participate in bone formation directly by differentiating toward the osteoblastic phenotype [4–6] or indirectly by secreting paracrine acting trophic factors that stimulate angiogenesis and regulate local inflammation. [7–10] Regardless of their contribution, long-term survival and engraftment of MSCs to defect sites is poor, [11, 12] drastically decreasing the therapeutic potential of MSC-based treatments.…”

Biomaterials for pluripotent stem cell engineering: from fate determination to vascularization

“…In contrast, our studies showed that mineralized biomaterials containing calcium phosphate minerals assist osteogenic differentiation of hESCs and hiPSCs in growth medium devoid of any osteogenic inducing soluble factors (58) . This finding suggests that the sole use of mineralized materials is sufficient to direct osteogenic commitment of hPSCs to form 3D bone tissues both in vitro and in vivo .…”

“…In addition to supporting differentiation, these mineralized biomaterials (e.g. Mineralized Polyethylene (glycol) Diacrylate) formed vascularized bone tissue when implanted in vivo (58) .…”

Augmentation of Musculoskeletal Regeneration: Role for Pluripotent Stem Cells

“…Here, scaffolds and various biomaterials have provided an invaluable tool for bone tissue engineering as they can enable a greater level of control over form and structure, and can also be supplemented with osteoinductive agents. Mineralized tissue formed by differentiated PSCs has been shown using various different scaffold materials [93,[124][125][126][127]. In these studies, the engineered tissue was subcutaneously implanted in animal models and in vivo mineralization capacity was evaluated; however, there is a lack of studies that have investigated the in vivo reparative effects of the PSC-derived engineered tissue.…”