Abstract
Human embryonic stem cells (hESC) have emerged as attractive candidates for cell-based therapies that are capable of restoring lost cell and tissue function. These unique cells are able to self-renew indefinitely and have the capacity to differentiate in to all three germ layers (ectoderm, endoderm and mesoderm). Harnessing the power of these pluripotent stem cells could potentially offer new therapeutic treatment options for a variety of medical conditions. Since the initial derivation of hESC lines in 1998, tremendous headway has been made in better understanding stem cell biology and culture requirements for maintenance of pluripotency. The approval of the first clinical trials of hESC cells for treatment of spinal cord injury and macular degeneration in 2010 marked the beginning of a new era in regenerative medicine. Yet it was clearly recognized that the clinical utility of hESC transplantation was still limited by several challenges. One of the most immediate issues has been the exposure of stem cells to animal pathogens, during hESC derivation and during in vitro propagation. Initial culture protocols used co-culture with inactivated mouse fibroblast feeder (MEF) or human feeder layers with fetal bovine serum or alternatively serum replacement proteins to support stem cell proliferation. Most hESC lines currently in use have been exposed to animal products, thus carrying the risk of xeno-transmitted infections and immune reaction. This mini review provides a historic perspective on human embryonic stem cell culture and the evolution of new culture models. We highlight the challenges and advances being made towards the development of xeno-free culture systems suitable for therapeutic applications.
Highlights
Human embryonic stem cells have emerged as exciting candidates for cell therapies in regenerative medicine due to their capacity to self-renew and differentiate into lineages of all three embryonic germ layers
Studies have demonstrated the ability of Human embryonic stem cells (hESC) to differentiate into a number of pathologically relevant cell types, including insulin-producing cells [1], neural precursor cells [2], cardiomyocytes [3], and hepatocyte-like cells [4], highlighting their potential to be used as a renewable cell source to treat major diseases such as type I diabetes, Parkinson’s disease, cardiovascular disease and liver diseases, among many others
Successful propagation of hESCs in a serum and xeno-free medium, TeSR1 using a combination of human matrix components collagen IV, laminin, vitronectin and fibronectin as a substratum marked a significant milestone in the development of clinically compliant hESC culture models [66,70]
Summary
Human embryonic stem cells (hESCs) have emerged as exciting candidates for cell therapies in regenerative medicine due to their capacity to self-renew and differentiate into lineages of all three embryonic germ layers. Use of chemically defined matrices and recombinant proteins based on ECM may be a more reliable approach towards xeno-free culture of therapeutic grade hESC lines. Successful propagation of hESCs in a serum and xeno-free medium, TeSR1 using a combination of human matrix components collagen IV, laminin, vitronectin and fibronectin as a substratum marked a significant milestone in the development of clinically compliant hESC culture models [66,70].
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