Most cited article - PubMed ID 23595287
Treating spinal cord injury in rats with a combination of human fetal neural stem cells and hydrogels modified with serotonin
Spinal cord injury (SCI) is a serious trauma, which often results in a permanent loss of motor and sensory functions, pain and spasticity. Despite extensive research, there is currently no available therapy that would restore the lost functions after SCI in human patients. Advanced treatments use regenerative medicine or its combination with various interdisciplinary approaches such as tissue engineering or biophysical methods. This review summarizes and critically discusses the research from specific interdisciplinary fields in SCI treatment such as the development of biomaterials as scaffolds for tissue repair, and using a magnetic field for targeted cell delivery. We compare the treatment effects of synthetic non-degradable methacrylate-based hydrogels and biodegradable biological scaffolds based on extracellular matrix. The systems using magnetic fields for magnetically guided delivery of stem cells loaded with magnetic nanoparticles into the lesion site are then suggested and discussed.
- Keywords
- Biomaterials, Cell delivery, Hydrogel, Magnetic field, Spinal cord injury,
- MeSH
- Biocompatible Materials pharmacology therapeutic use MeSH
- Hydrogels therapeutic use MeSH
- Humans MeSH
- Magnetic Field Therapy methods trends MeSH
- Spinal Cord Injuries physiopathology therapy MeSH
- Nerve Regeneration drug effects physiology MeSH
- Stem Cell Transplantation methods trends MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Biocompatible Materials MeSH
- Hydrogels MeSH
Spinal cord injury (SCI), is a devastating condition leading to the loss of locomotor and sensory function below the injured segment. Despite some progress in acute SCI treatment using stem cells and biomaterials, chronic SCI remains to be addressed. We have assessed the use of laminin-coated hydrogel with dual porosity, seeded with induced pluripotent stem cell-derived neural progenitors (iPSC-NPs), in a rat model of chronic SCI. iPSC-NPs cultured for 3 weeks in hydrogel in vitro were positive for nestin, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2). These cell-polymer constructs were implanted into a balloon compression lesion, 5 weeks after lesion induction. Animals were behaviorally tested, and spinal cord tissue was immunohistochemically analyzed 28 weeks after SCI. The implanted iPSC-NPs survived in the scaffold for the entire experimental period. Host axons, astrocytes and blood vessels grew into the implant and an increased sprouting of host TH+ fibers was observed in the lesion vicinity. The implantation of iPSC-NP-LHM cell-polymer construct into the chronic SCI led to the integration of material into the injured spinal cord, reduced cavitation and supported the iPSC-NPs survival, but did not result in a statistically significant improvement of locomotor recovery.
- Keywords
- Chronic spinal cord injury, HEMA hydrogel, human induced pluripotent stem cells, laminin, neural progenitors, surface charge,
- MeSH
- Cell Differentiation MeSH
- Chronic Disease MeSH
- Hydrogels MeSH
- Induced Pluripotent Stem Cells metabolism MeSH
- Rats MeSH
- Neural Stem Cells transplantation MeSH
- Spinal Cord Injuries therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hydrogels MeSH
While many types of biomaterials have been evaluated in experimental spinal cord injury (SCI) research, little is known about the time-related dynamics of the tissue infiltration of these scaffolds. We analyzed the ingrowth of connective tissue, axons and blood vessels inside the superporous poly (2-hydroxyethyl methacrylate) hydrogel with oriented pores. The hydrogels, either plain or seeded with mesenchymal stem cells (MSCs), were implanted in spinal cord transection at the level of Th8. The animals were sacrificed at days 2, 7, 14, 28, 49 and 6 months after SCI and histologically evaluated. We found that within the first week, the hydrogels were already infiltrated with connective tissue and blood vessels, which remained stable for the next 6 weeks. Axons slowly and gradually infiltrated the hydrogel within the first month, after which the numbers became stable. Six months after SCI we observed rare axons crossing the hydrogel bridge and infiltrating the caudal stump. There was no difference in the tissue infiltration between the plain hydrogels and those seeded with MSCs. We conclude that while connective tissue and blood vessels quickly infiltrate the scaffold within the first week, axons show a rather gradual infiltration over the first month, and this is not facilitated by the presence of MSCs inside the hydrogel pores. Further research which is focused on the permissive micro-environment of the hydrogel scaffold is needed, to promote continuous and long-lasting tissue regeneration across the spinal cord lesion.
- MeSH
- Axons pathology MeSH
- Biocompatible Materials chemistry MeSH
- Time Factors MeSH
- Neovascularization, Physiologic MeSH
- Hydrogels MeSH
- Rats MeSH
- Oligopeptides chemistry MeSH
- Polyhydroxyethyl Methacrylate chemistry MeSH
- Spinal Cord Injuries pathology physiopathology therapy MeSH
- Porosity MeSH
- Rats, Wistar MeSH
- Spinal Cord Regeneration physiology MeSH
- Materials Testing MeSH
- Tissue Scaffolds chemistry MeSH
- Mesenchymal Stem Cell Transplantation * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Names of Substances
- Biocompatible Materials MeSH
- Hydrogels MeSH
- Oligopeptides MeSH
- Polyhydroxyethyl Methacrylate MeSH
- seryl-isoleucyl-lysyl-valyl-alanyl-valinamide MeSH Browser
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