Promise Of Pluripotent Stem Cells Research Articles

The past, present, and future promise of pluripotent stem cells

In this commentary article, we take the view in support of the continued promise of pluripotent stem cell (PSC) research and the potential for curative PSC-derived treatments to be realized within our lifetimes. We address a prominent critique of the PSC field: the failure to-date to successfully transplant lab-grown organs into human patients or to reproducibly demonstrate curative PSC-derived therapies in the clinic.We also discuss the key biological concept of cellular maturation, which is relevant to the eventual widespread clinical application of PSC-therapies. We then examine how an exciting development in the field of genomic engineering has opened up new avenues for discovery in PSC research. Finally, we will comment on possibilities for the future, informed by our experience of actively participating in this research for more than a decade.

Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective.

Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

Livestock models for exploiting the promise of pluripotent stem cells.

Livestock species are widely used as biomedical models. Pigs, in particular, are beginning to have a significant role in regenerative medicine for testing the applicability, success, and safety of grafts derived from induced pluripotent stem cells. Animal testing must always be performed before any clinical trials are performed in humans, and pigs may sometimes be the species of choice because of their physiological and anatomical similarities to humans. Induced pluripotent stem cells (iPSC) have been generated with some success from livestock species by a variety of reprogramming procedures, but authenticated embryonic stem cells (ESC) have not. There are now several studies in which porcine iPSC have been tested for their ability to provide functional grafts in pigs. Pigs have also served as recipients for grafts derived from human iPSC. There have also been recent advances in creating pigs with severe combined immunodeficiency (SCID). Like SCID mice, these pigs are expected to be graft tolerant. Additionally, chimeric, partially humanized pigs could be sources of human organs. Another potential application of pluripotent stem cells from livestock is for the purpose of differentiating the cells into skeletal muscle, which, in turn, could be used either to produce cultured meat or to engraft into damaged muscle. None of these technologies has advanced to a stage that they have become mainstream, however. Despite the value of livestock models in regenerative medicine, only a limited number of institutions are able to use these animals.

Innovative animal component-free surface for the cultivation of human embryonic stem cells

Background The promise of pluripotent stem cells lies in their ability to form any cell or tissue in the body. However, this promise requires a stable and reproducible method to grow the cells. Current methods rely on feeder cells or extracellular matrix proteins to cover the cultureware growth surface, and either manual selection or enzymatic dissociation in cell passaging and harvesting. This study describes a novel and simple method to grow pluripotent stem cells without the use of feeder cells or extracellular matrix proteins.

Overexpression of BCL2 enhances survival of human embryonic stem cells during stress and obviates the requirement for serum factors

The promise of pluripotent stem cells as a research and therapeutic tool is partly undermined by the technical challenges of generating and maintaining these cells in culture. Human embryonic stem cells (hESCs) are exquisitely sensitive to culture conditions, and require constant signaling by growth factors and cell-cell and cell-matrix interactions to prevent apoptosis, senescence, and differentiation. Previous work from our laboratory demonstrated that overexpression of the prosurvival gene BCL2 in mouse embryonic stem cells overrode the requirement of serum factors and feeder cells to maintain mESCs in culture. To determine whether this prosurvival gene could similarly protect hESCs, we generated hESC lines that constitutively or inducibly express BCL2. We find that BCL2 overexpression significantly decreases dissociation-induced apoptosis, resulting in enhanced colony formation from sorted single cells, and enhanced embryoid body formation. In addition, BCL2-hESCs exhibit normal growth in the absence of serum, but require basic fibroblast growth factor to remain undifferentiated. Furthermore, they maintain their pluripotency markers, form teratomas in vivo, and differentiate into all three germ layers. Our data suggest that the BCL2 signaling pathway plays an important role in inhibiting hESC apoptosis, such that its overexpression in hESCs offers both a survival benefit in conditions of stress by resisting apoptosis and obviates the requirement for serum or a feeder layer for maintenance.