RESUMO
Cell therapy is a promising treatment for diseases that are caused by cell degeneration or death. The cells for clinical transplantation are usually obtained by culturing healthy allogeneic or exogenous tissue in vitro. However, for diseases of the eye, obtaining the adequate number of cells for clinical transplantation is difficult due to the small size of tissue donors and the frequent needs of long-term amplification of cells in vitro, which results in low cell viability after transplantation. In addition, the transplanted cells often develop fibrosis or degrade and have very low survival. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS) are also promising candidates for cell therapy. Unfortunately, the differentiation of ESCs can bring immune rejection, tumorigenicity and undesired differentiated cells, limiting its clinical application. Although iPS cells can avoid the risk of immune rejection caused by ES cell differentiation post-transplantation, the low conversion rate, the risk of tumor formation and the potentially unpredictable biological changes that could occur through genetic manipulation hinder its clinical application. Thus, the desired clinical effect of cell therapy is impaired by these factors. Recent research findings recognize that the reason for low survival of the implanted cells not only depends on the seeded cells, but also on the cell microenvironment, which determines the cell survival, proliferation and even reverse differentiation. When used for cell therapy, the transplanted cells need a specific three-dimensional structure to anchor and specific extra cellular matrix components in addition to relevant cytokine signaling to transfer the required information to support their growth. These structures present in the matrix in which the stem cells reside are known as the stem cell microenvironment. The microenvironment interaction with the stem cells provides the necessary homeostasis for cell maintenance and growth. A large number of studies suggest that to explore how to reconstruct the stem cell microenvironment and strengthen its combination with the transplanted cells are key steps to successful cell therapy. In this review, we will describe the interactions of the stem cell microenvironment with the stem cells, discuss the importance of the stem cell microenvironment for cell-based therapy in ocular diseases, and introduce the progress of stem cell-based therapy for ocular diseases.
RESUMO
OBJECTIVE: To observe the efficacy and safety of 0.5% Loteprednol Etabonate ophthalmic suspension in the treatment of moderate dry eye. METHODS: Totally 34 dry eye patients (68 eyes) in grade 2 or grade 3 (DEWS standard) enrolled in our hospital from March 2009 to September 2010 were randomly divided into two groups: the experimental group (Loteprednol Etabonate Group) and the control group (Cyclosporine A, CsA group). 0.5% Loteprednol Etabonate ophthalmic suspension or 1% CsA eye drops was applied 2 times a day respectively together with 0.2% Liposic eye drops (4 - 6 times/day). Questionnaire was used in these patients before the treatment and repeated every 2 weeks during the treatment till 8 weeks. Slit lamp microscope examination, fluorescent staining, tear break-up time (BUT), Schirmer I test (SIt) and intraocular pressure measurement were carried out at the same time point. The conjunctival impression cytology (IC) was performed before the treatment and 8 weeks after the treatment. The mean of the results were compared by t-tests and χ(2) test. RESULTS: After 2 weeks of the treatment, the mean score of the questionnaire was significantly lower than that before the treatment in each group (t = 5.36, 3.63, P < 0.01). After 4 weeks of the treatment, the inflammation of the ocular surface was relieved obviously in both group and the mean score of the corneal fluorescein staining (FL) was lower than that before the treatment in each group. The average density of the goblet cells before the treatment was (181.2 ± 16.1)/mm(2) and (179.4 ± 17.5)/mm(2) in each group respectively. After 8 weeks of the treatment, this increased to (348.6 ± 22.5)/mm(2) and (360.4 ± 27.8)/mm(2) significantly (t = 16.9, 16.3, P < 0.05). BUT was significantly prolonged in each group after the treatment (P < 0.01). There was no significant change in ST I or NCT in each group (P > 0.05). CONCLUSIONS: Topical 0.5% Loteprednol Etabonate ophthalmic suspension is safe and effective for the treatment of moderate dry eye.
