Bone-chip system to monitor osteogenic differentiation using optical imaging.

Human organoids and organ-on-chip systems to predict human responses to new therapies and for the understanding of disease mechanisms are being more commonly used in translational research. We have developed a bone-chip system to study osteogenic differentiation in vitro, coupled with optical imaging approach which provides the opportunity of monitoring cell survival, proliferation and differentiation in vitro without the need to terminate the culture. We used the mesenchymal stem cell (MSC) line over-expressing bone morphogenetic protein-2 (BMP-2), under Tet-Off system, and reporter gene under constitutive promoter.

Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

Background: A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures.

Teriparatide attenuates scarring around murine cranial bone allograft via modulation of angiogenesis.

Nearly all bone fractures in humans can deteriorate into a non-union fracture, often due to formation of fibrotic tissue. Cranial allogeneic bone grafts present a striking example: although seemingly attractive for craniofacial reconstructions, they often fail due to fibrosis at the host-graft junction, which physically prevents the desired bridging of bone between the host and graft and revitalization of the latter. In the present study we show that intermittent treatment with recombinant parathyroid hormone-analogue (teriparatide) modulates neovascularization feeding in the graft surroundings, consequently reducing fibrosis and scar tissue formation and facilitates osteogenesis.

Environmental manipulation to promote stem cell survival in vivo: use of aggregation, oxygen carrier, and BMP-2 co-delivery strategies.

While mesenchymal stem cell (MSC)-based strategies for critically-sized bone defect repair hold promise, poor cell survival in vivo remains a significant barrier to the translation of these therapeutics. One method employed to extend the survival of MSCs is the formation of three-dimensional aggregates, a strategy which modulates the immunomodulatory secretome of the cells, thereby influencing the local inflammatory environment and potentially bone tissue repair. Enrichment of cell-seeded hydrogels with oxygen carriers to counter the hypoxic conditions encountered in vivo or co-delivery of cells with growth factors, are also strategies employed to modulate the cell micro-environment.

Computed Tomography and Optical Imaging of Osteogenesis-angiogenesis Coupling to Assess Integration of Cranial Bone Autografts and Allografts.

A major parameter determining the success of a bone-grafting procedure is vascularization of the area surrounding the graft. We hypothesized that implantation of a bone autograft would induce greater bone regeneration by abundant blood vessel formation. To investigate the effect of the graft on neovascularization at the defect site, we developed a micro-computed tomography (µCT) approach to characterize newly forming blood vessels, which involves systemic perfusion of the animal with a polymerizing contrast agent.

BMP6-Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study.

Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF), suffer grave financial and clinical burden. Current clinical treatments focus on symptoms' management but do not combat the issue at the source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing the BMP6 gene (MSC-BMP6), were suspended in fibrin gel and implanted into a vertebral defect to investigate their effect on bone regeneration in a clinically relevant, large animal pig model.

PTH promotes allograft integration in a calvarial bone defect.

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter.

Gene-modified adult stem cells regenerate vertebral bone defect in a rat model.

Vertebral compression fractures (VCFs), the most common fragility fractures, account for approximately 700,000 injuries per year. Since open surgery involves morbidity and implant failure in the osteoporotic patient population, a new minimally invasive biological solution to vertebral bone repair is needed. Previously, we showed that adipose-derived stem cells (ASCs) overexpressing a BMP gene are capable of inducing spinal fusion in vivo.