Frontiers in Stem Cell and Regenerative Medicine Research

Normal bone remodeling requires a continuous supply of osteoblasts and osteoclasts from stem cells in the bone marrow. In bone-related diseases and fractures, this process becomes disrupted. There are a number of therapeutic strategies being employed that are attempting to repair diseased or damaged bone, including bone grafts, demineralized bone implantation, and recombinant protein treatments. However, likely more than these strategies, stem cells hold great potential to completely regenerate bone tissue. In this chapter, we provide a discussion on the physiology and pathophysiology of osteogenesis, as well as current therapies for bony defects, with specific emphasis placed on the advantages of utilizing various types of stem cells as therapeutic approaches to treat bone-related diseases and difficult-to-heal fractures.

Neonatal brain injury encompasses hypoxic-ischemic encephalopathy (HIE), perinatal stroke, and white matter injury. The estimated incidence of HIE in developed countries is 1.5 in 1,000 live births. Hypothermia therapy improves neurodevelopmental outcomes in only 53% of treated HIE patients. Perinatal stroke occurs in 1 per 1,600 births and is a major cause of cerebral palsy and developmental impairments. Periventricular white matter injury affects 50% of premature neonates and accounts for 90% of neurologic deficits in survivors.

Stem cell therapy has emerged as a potential treatment for neonatal brain injury. This review will present the state of the art for stem cell therapy in neonatal brain injury.

Neurodegenerative, neurological, and psychiatric diseases (NNPDs) significantly contribute to disability and mortality worldwide. Despite numerous studies, only few effective therapeutic methods and drugs have been found so far even for the most common diseases, such as Alzheimer’s and Parkinson’s diseases. The lack of effective therapeutic methods is mainly explainable by the absence of relevant in vitro model systems to study pathological phenotypes at the cellular and molecular levels. Induced pluripotent stem cells are a unique source of different types of patientspecific neurons that can reproduce in vitro the specific features of individual diseases. In this chapter, the cell models based on patient-specific induced pluripotent stem cellderived neurons and their use in the search for new drugs and toxicological studies are described in detail. In addition, the utility of genome engineering for the creation and study of cell models for NNPDs is discussed.

Respiratory diseases represent a wide array of most common diseases with great social and financial burden. Despite the obvious progress in the treatment of patients with respiratory pathology, achieved in the last decade, there are still many incurable disorders such as emphysema, pulmonary fibrosis, cystic fibrosis, acute respiratory distress syndrome, pulmonary hypertension, etc. The results of treatment of these disorders are far from perfect and often the only today alternative is lung transplantation. Regenerative medicine could become a new solution, offering real tools for severe and progressive lung diseases. To date, numerous preclinical studies have proven the effectiveness of regenerative technologies in different animal models and in addition quite a few clinical trials have been started with the first results. This review critically evaluates the data obtained in the experimental and clinical studies, with the emphasis on advances and limitations of regenerative medicine.

The focus of the chapter is to review current novel tissue engineering approaches for the esophagus. Patients suffering from esophageal defects and disease are commonly treated with surgical intervention, which can lead to a host of short and long term complications including the need for repeated surgery. The diseased segment or defect is replaced with either stomach, colon or small intestine from that patient, which lacks the motility to function as an esophageal replacement. Therefore, a new surgical therapeutic option is needed that can be tailored to each patient and be comprised of autologous cells. Many researchers have evaluated the use of native or synthetic matrix as a scaffold for bridging the gap. The cells used on these scaffolds have ranged from cells isolated from the native esophagus, pluripotent stem cells, mesenchymal stem cells and even fibroblasts. When these scaffolds and cells have been introduced in animal models, those scaffolds seeded with cells show a positive outcome with integration into host tissue and lack of a large immune response. The opposite was seen when scaffolds were implanted without any cells seeded on them. These implantation studies have also been done in larger animals and allowed to incubate for months and demonstrate anatomy similar to that of native esophagus but further studies are needed to better understand the mechanism for this result as well as what combinations of cells and scaffolding yield a positive result for the patient.