Importance of the stem cell microenvironment for ophthalmological cell-based therapy

Abstract

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 448March 26, 2015|Volume 7|Issue 2|

Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment

“…However, the risks of potential tumor development and other unpredictable biological changes during transplantation are still unresolved. The cellular interaction of transplanted cells in the microenvironment has been reported important to obtain successful results in regeneration therapy [13] . Recently, we demonstrated that the microenvironment of cancer cells can affect stem cells to convert iPSCs into CSC-like cells, with tumorigenic capacity as well as self-renewal and differentiation potential.…”

Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats

“…In addition, the poor viability of transplanted BMSCs might be related to the hostile survival microenvironment 15. The vasculature plays an instructive role in the stem cell niche16 whereas a growing body of evidence has indicated that diabetes impacts angiogenesis through a variety of mechanisms, including vascular endothelial growth factor (VEGF)/phosphoinositide 3’ kinase/AKT/endothelial nitric oxide synthase (eNOS) proangiogenic pathway abrogation and vessel (CD31 + ) number reduction 1718…”

Phenotypes and transdifferentiation of transplanted oral mucosal epithelial cells for limbal stem cell deficiency

“…The microenvironment is greatly involved in the success of stem cell transplant and the long-term survival of the graft in ocular surface therapy. 23 In cultivated limbal epithelial transplantation, Tsai et al found that the intact amniotic membrane could provide the niche environment for cultured limbal stem cells and maintain the limbal-like environment, which cell survival related to the severity of the disease. 24 In general, the microenvironment has a central role in the survival and renewal of limbal stem cells.…”