Temporal bone reconstruction is a persisting problem following middle ear cholesteatoma surgery. Seeking to advance the clinical transfer of stem cell therapy we attempted the reconstruction of temporal bone using a composite bioartificial graft based on a hydroxyapatite bone scaffold combined with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The aim of this study was to evaluate the effect of the combined biomaterial on the healing of postoperative temporal bone defects and the preservation of physiological hearing functions in a guinea pig model. The treatment's effect could be observed at 1 and 2 months after implantation of the biomaterial, as opposed to the control group. The clinical evaluation of our results included animal survival, clinical signs of an inflammatory response, and exploration of the tympanic bulla. Osteogenesis, angiogenesis, and inflammation were evaluated by histopathological analyses, whereas hBM-MSCs survival was evaluated by immunofluorescence assays. Hearing capacity was evaluated by objective audiometric methods, i.e. auditory brainstem responses and otoacoustic emission. Our study shows that hBM-MSCs, in combination with hydroxyapatite scaffolds, improves the repair of bone defects providing a safe and effective alternative in their treatment following middle ear surgery due to cholesteatoma.

• Keywords
• Cholesteatoma, Ear function, Mesenchymal stromal cells, Osteogenesis, Scaffold, Temporal bone,
• MeSH
• Cholesteatoma, Middle Ear * metabolism   pathology   surgery   MeSH
• Heterografts MeSH
• Humans MeSH
• Mastoidectomy adverse effects   MeSH
• Disease Models, Animal MeSH
• Guinea Pigs MeSH
• Recovery of Function * MeSH
• Osteogenesis * MeSH
• Postoperative Complications * metabolism   pathology   therapy   MeSH
• Hearing * MeSH
• Temporal Bone * injuries   metabolism   pathology   MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Guinea Pigs MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE: Vertebral body defects represent one of the most common orthopedic challenges. In order to advance the transfer of stem cell therapies into orthopedic clinical practice, we performed this study to evaluate the safety and efficacy of a composite bioartificial graft based on a hydroxyapatite bone scaffold (CEM-OSTETIC(®)) combined with human mesenchymal stem cells (MSCs) in a rat model of vertebral body defects. METHODS: Under general isoflurane anesthesia, a defect in the body of the L2 vertebra was prepared and left to heal spontaneously (group 1), implanted with scaffold material alone (group 2), or implanted with a scaffold together with 0.5 million MSCs (group 3) or 5 million MSCs (group 4). The rats were killed 8 weeks after surgery. Histological and histomorphometrical evaluation of the implant as well as micro-CT imaging of the vertebrae were performed. RESULTS: We observed a significant effect on the formation of new bone tissue in the defect in group 4 when compared to the other groups and a reduced inflammatory reaction in both groups receiving a scaffold and MSCs. We did not detect any substantial pathological changes or tumor formation after graft implantation. CONCLUSIONS: MSCs in combination with a hydroxyapatite scaffold improved the repair of a model bone defect and might represent a safe and effective alternative in the treatment of vertebral bone defects.

• MeSH
• Lumbar Vertebrae diagnostic imaging   injuries   pathology   MeSH
• Wound Healing MeSH
• Durapatite * MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Random Allocation MeSH
• Spinal Injuries diagnostic imaging   pathology   therapy   MeSH
• Rats, Wistar MeSH
• Radiography MeSH
• Tissue Engineering methods   MeSH
• Tissue Scaffolds * MeSH
• Bone Transplantation methods   MeSH
• Mesenchymal Stem Cell Transplantation methods   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Durapatite * MeSH

Electrospun gelatin and poly-ε-caprolactone (PCL) nanofibers were prepared using needleless technology and their biocompatibility and therapeutic efficacy have been characterized in vitro in cell cultures and in an experimental model of a skin wound. Human dermal fibroblasts, keratinocytes and mesenchymal stem cells seeded on the nanofibers revealed that both nanofibers promoted cell adhesion and proliferation. The effect of nanofibers on wound healing was examined using a full thickness wound model in rats and compared with a standard control treatment with gauze. Significantly faster wound closure was found with gelatin after 5 and 10 days of treatment, but no enhancement with PCL nanofibers was observed. Histological analysis revealed enhanced epithelialisation, increased depth of granulation tissue and increased density of myofibroblasts in the wound area with gelatin nanofibers. The results show that gelatin nanofibers produced by needleless technology accelerate wound healing and may be suitable as a scaffold for cell transfer and skin regeneration.

• MeSH
• Biocompatible Materials * MeSH
• Wound Healing * MeSH
• Humans MeSH
• Nanofibers * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biocompatible Materials * MeSH

Adipose-derived stromal cells (ASCs) are an alternative source of stem cells for cell-based therapies of neurological disorders such as spinal cord injury (SCI). In the present study, we predifferentiated ASCs (pASCs) and compared their behavior with naïve ASCs in vitro and after transplantation into rats with a balloon-induced compression lesion. ASCs were predifferentiated into spheres before transplantation, then pASCs or ASCs were injected intraspinally 1 week after SCI. The cells' fate and the rats' functional outcome were assessed using behavioral, histological, and electrophysiological methods. Immunohistological analysis of pASCs in vitro revealed the expression of NCAM, NG2, S100, and p75. Quantitative RT-PCR at different intervals after neural induction showed the up-regulated expression of the glial markers NG2 and p75 and the neural precursor markers NCAM and Nestin. Patch clamp analysis of pASCs revealed three different types of membrane currents; however, none were fast activating Na(+) currents indicating a mature neuronal phenotype. Significant improvement in both the pASC and ASC transplanted groups was observed in the BBB motor test. In vivo, pASCs survived better than ASCs did and interacted closely with the host tissue, wrapping host axons and oligodendrocytes. Some transplanted cells were NG2- or CD31-positive, but no neuronal markers were detected. The predifferentiation of ASCs plays a beneficial role in SCI repair by promoting the protection of denuded axons; however, functional improvements were comparable in both the groups, indicating that repair was induced mainly through paracrine mechanisms.

• MeSH
• Cell Differentiation physiology   MeSH
• Stromal Cells transplantation   MeSH
• Behavior, Animal physiology   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Patch-Clamp Techniques MeSH
• Multipotent Stem Cells cytology   physiology   MeSH
• Motor Activity physiology   MeSH
• Spinal Cord Injuries pathology   surgery   MeSH
• Rats, Sprague-Dawley MeSH
• Rats, Transgenic MeSH
• Rats, Wistar MeSH
• Stem Cell Transplantation methods   MeSH
• Adipose Tissue cytology   physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH