Bone Defect Repair Using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord

Abstract

Objective. Bone defects or atrophy may arise as a consequence of injury, inflammation of various etiologies, and neoplastic or traumatic processes or as a result of surgical procedures. Sometimes the regeneration process of bone loss is impaired, significantly slowed down, or does not occur, e.g., in congenital defects. For the bone defect reconstruction, a piece of the removed bone from ala of ilium or bone transplantation from a decedent is used. Replacement of the autologous or allogenic source of the bone-by-bone substitute could reduce the number of surgeries and time in the pharmacological coma during the reconstruction of the bone defect. Application of mesenchymal stem cells in the reconstruction surgery may have positive influence on tissue regeneration by secretion of angiogenic factors, recruitment of other MSCs, or differentiation into osteoblasts. Materials and Methods. Mesenchymal stem cells derived from the umbilical cord (Wharton’s jelly (WJ-MSC)) were cultured in GMP-grade DMEM low glucose supplemented with heparin, 10% platelet lysate, glucose, and antibiotics. In vitro WJ-MSCs were seeded on the bone substitute Bio-Oss Collagen® and cultured in the StemPro® Osteogenesis Differentiation Kit. During the culture on the 1st, 7th, 14th, and 21st day (day in vitro (DIV)), we analyzed viability (confocal microscopy) and adhesion capability (electron microscopy) of WJ-MSC on Bio-Oss scaffolds, gene expression (qPCR), and secretion of proteins (Luminex). In vivo Bio-Oss® scaffolds with WJ-MSC were transplanted to trepanation holes in the cranium to obtain their overgrowth. The computed tomography was performed 7, 14, and 21 days after surgery to assess the regeneration. Results. The Bio-Oss® scaffold provides a favourable environment for WJ-MSC survival. WJ-MSCs in osteodifferentiation medium are able to attach and proliferate on Bio-Oss® scaffolds. Results obtained from qPCR and Luminex® indicate that WJ-MSCs possess the ability to differentiate into osteoblast-like cells and may induce osteoclastogenesis, angiogenesis, and mobilization of host MSCs. In animal studies, WJ-MSCs seeded on Bio-Oss® increased the scaffold integration with host bone and changed their morphology to osteoblast-like cells. Conclusions. The presented construct consisted of Bio-Oss®, the scaffold with high flexibility and plasticity, approved for clinical use with seeded immunologically privileged WJ-MSC which may be considered reconstructive therapy in bone defects.

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

“…Review of available literature supports the idea of using PL as a non-zoonotic adjuvant for cell culture in clinical research. It was proved that regeneration of bone and cartilage after application of MSCs combined with biomaterials takes place due to tissue replacement [44][45][46] . In case of neurological disorders, replacement mechanism of regeneration is disputable, however neuro-therapeutic potential of MSCs applied within hydrogel was observed due to their secretory properties, such as production of immunomodulatory or neurogenic factors 47 .…”

Strategies for Bone Regeneration: From Graft to Tissue Engineering

“…The addition of MSCs to the composite biomaterial poly(3-hydroxybutyrate)/HA/alginate improves the regenerative potential, increasing bone formation in a critical-size defect by approximately four-fold [ 171 ]. Kosinski et al demonstrated the regeneration that occurred after 21 days of transplantation of umbilical cord derived MSCs seeded onto a scaffold of Geistlich Bio-Oss ® Collagen in a cranial defect [ 187 ]. Although their toxicity to eukaryotic cells is still under investigation [ 188 , 189 , 190 ], silver nanoparticles could promote the proliferation and osteogenesis of mesenchymal stem cells and improve femoral fracture healing when encapsulated in collagen and used at low concentrations [ 191 ].…”

Umbilical Cord Mesenchymal Stromal Cells for Cartilage Regeneration Applications

“…BMP2, 4, 6, 7, and 9 have been reported to induce in vitro chondrogenesis of human MSCs [ 57 ]. UC-MSCs have been demonstrated to secrete BMP2 in vitro and to induce the increase of endogenous BMP4, 5, and 7 levels in vivo [ 58 – 60 ]. In addition, UC-MSCs induce overexpression of GDF5/BMP14/CDMP1, promoting chondrogenic differentiation in cocultures with fibroblast-like synoviocytes, thus, suggesting their potential in cartilage repair [ 61 ].…”