Current Tissue Engineering (Discontinued) - Volume 5, Issue 1, 2016

Background: Bone loss due to congenital or acquired abnormalities of the craniofacial skeleton is of common occurrence. Surgical repair and reconstruction of the critical size bony defects are clinically challenging. Of the several approaches, stem cell-based bone-regeneration is gaining momentum. Stem cells from the orofacial region have been identified as potential source for craniofacial bone reconstruction as they are derived from cranial neural crest cells. Isolation of orofacial stem cells is minimally invasive, and they are highly proliferative with the ability to differentiate into multiple lineages. Method: The current review gives a description on mesenchymal stem cells derived from the orofacial region (OMSCs) and updates the information on their use in bone regeneration. Results: Studies have reported that OMSCs are highly proliferative with the ability to differentiate into osteogenic lineage. Various factors influencing osteogenic potential of OMSCs have been discussed. Conclusion: The findings from the previous literature confirms the potential use of OMSCs in craniofacial bone tissue engineering.

Chronic degenerative retinopathies are the leading causes of irreversible vision loss and blindness worldwide. There are limited treatment options for these conditions due to the lack of effective drug delivery system. Currently, to slow disease progression, invasive and repeated drug administrations into the vitreous are clinically performed. Encapsulated cell therapy (ECT) is a promising approach for delivery of therapeutics to the retina in a safe, controlled, stable and long-term manner. By utilizing cells as a source of drug production and isolating them from the host immune system with biomaterial scaffolds, ECT enables the delivery of freshly synthesized therapeutics over prolonged periods of time at the targeted location. Although ECT has been widely explored in treating neurological disorders in the central nervous system, its application in the eye is a relative new area of research. This review paper intends to discuss the characteristic of the eye as a target for ECT and the various parameters for optimizing ECT for ocular applications. Also, the current development of ECT in retinal degenerative diseases is discussed. Further advancement in ocular drug development and optimization of scaffold and cell performance in the ocular environment can potentiate the application of ECT over a broad range of debilitating posterior ocular disorders.

Retinal ganglion cell (RGC) degeneration is one of the major causes for blindness, a condition widely attributed to the pathology of RGC axons. How to promote the affected RGC axons to regenerate is currently under intense investigation. Difficulties in adult RGC axons to regenerate are due partially to the attenuated intrinsic re-growth ability, and further complicated by factors located in the unfavorable microenvironments, especially the myelin sheath and the activated glia cells. Additionally, axon damage often induces RGC death, eliminating any chance for axon regeneration, and therefore further complicates the treatment for RGC degeneration. In this review, we discuss the different aspects that cause regeneration failure in the RGC axons, and also the currently known factors that promote RGC axon regeneration ability. These findings are encouraging and open the possibility that clinically meaningful regeneration may become achievable one day in the future.

Regenerative medicine (RM) possesses the ability to repair injured as well as aging cells, tissues and organs. This review discusses the recent advances, future prospects and challenges in the field of RM mainly the stem cell therapy in degenerative retinal diseases such as age related macular degeneration (AMD), retinitis pigmentosa (RP) and Stargardt disease (STGD). Stem cell lines like retinal progenitor cells, induced pluripotent stem cells, mesenchymal stem cells, embryonic stem cells and very small embryonic-like stem cells have potential application in the degenerative retinal diseases where they have the potency to regenerate the injured and damaged photoreceptors and retinal neurons ultimately restoring and enhancing the visual functions. Stem cell transplantation for AMD, RP and STGD is currently transforming from bench side research to bedside which may eventually allow the progress of the more advanced therapies. In future, stem cell therapy could be combined with bioengineered products and small molecules to produce novel therapies in the field of ophthalmology particularly in terms of visual recovery to fight against blindness.

Retinal degeneration due to injury or disease can be a devastating event to the quality of life of an individual. Efforts to develop strategies for retinal repair and regeneration have been challenging due to the complexities in the microenvironment necessary to support and maintain retinal function, as well as the difficulty in guiding the correct integration of regenerating cells to the existing neural networks. Stem cell therapies have recently emerged as a viable option to promote retinal repair and regeneration with encouraging results. As more studies are performed on the effect of stem cells on the regenerative processes in the retina, it becomes clear that stem cells can play a beneficial role not only by their differentiation capabilities and cellular replacement potential, but also as modulators of local environmental factors to provide conditions that are more conducive to functional repair and regeneration. Stem cells have been shown to be able to modulate several processes that are detrimental to regeneration such as inflammation, extracellular matrix remodeling, and loss of trophic support, among others. Here we review some of the latest studies on stem cell-mediated retinal regeneration by focusing primarily on how stem cells can modulate the microenvironment in the neural retina to augment its regenerative potential following injury or disease.

Background: Age-related macular degeneration (AMD) is a progressive degenerative disease of the macula and is the leading cause of visual impairment in the elderly population worldwide. The two advanced forms of AMD are geographic atrophy and choroidal neovascularization (CNV) which are the major causes of visual loss in AMD patients. Clinically effective therapy for CNV is now available but is limited by the need for repeated intravitreal injections of anti-angiogenic agents. There is still no effective treatment for geographic atrophy. Earlier concepts on AMD therapy were confined to local ocular therapies. However, recent evidences show that the complement system, inflammatory response and oxidative stress level are altered in the systemic circulation of AMD patients. Meanwhile, within regenerative medicine, stem cell therapy is effectively alleviating these systemic changes in multiple diseases. These findings have provided new insight into the pathophysiology and subsequent potential for clinical interventions in AMD. Methods: This review article will first summarize the pathophysiology of AMD and then describe the systemic disorders associated with AMD. In addition, the characteristics of mesenchymal stem cells (MSCs) in regenerative medicine and its potential therapeutic effect for systemic disorders will also be discussed. Results: AMD is an oxidative stress and inflammation-related disease affecting the RPE and photoreceptor cells of the macula. It is not only a localized eye disease, but also a disease affected by the systemic status of the patient. There is good evidence to show the influence of systemic factors in the pathogenesis, including complement system, inflammation, oxidative stress and angiogenic factors. Since MSCs possess the paracrine effects of anti-oxidation, anti-inflammation and immunomodulation, systemic administration of MSCs could theoretically alter the systemic influence on AMD progression. Currently, there are 3 MSC clinical trials on AMD, which locally apply bone marrow and adipose tissue-derived MSCs to supply neurotrophic factors to the microenvironment. Conclusion: MSCs hold promises for treating the systemic conditions associated with AMD. The anti-inflammatory and anti-oxidative effects of MSCs are desirable and be developed as a potential therapeutic strategy against AMD for clinical treatment in the future.