Systematic Review of Induced Pluripotent Stem Cell Technology as a Potential Clinical Therapy for Spinal Cord Injury

Abstract

Transplantation therapies aimed at repairing neurodegenerative and neuropathological conditions of the central nervous system (CNS) have utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages. The use and popularity of each cell type is guided by a number of factors including the nature of the experimental model, neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cells' myelination capability. The promise of stem cells, with their reported ability to give rise to neuronal lineages to replace lost endogenous cells and myelin, integrate into host tissue, restore functional connectivity, and provide trophic support to enhance and direct intrinsic regenerative ability, has been seen as a most encouraging step forward. The advent of the induced pluripotent stem cell (iPSC), which represents the ability to "reprogram" somatic cells into a pluripotent state, hails the arrival of a new cell transplantation candidate for potential clinical application in therapies designed to promote repair and/or regeneration of the CNS. Since the initial development of iPSC technology, these cells have been extensively characterized in vitro and in a number of pathological conditions and were originally reported to be equivalent to embryonic stem cells (ESCs). This review highlights emerging evidence that suggests iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations, which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies. It also highlights the limitations of current technologies used to generate these cells. Moreover, we provide a systematic review of the state of play with regard to the use of iPSCs in the treatment of neurodegenerative and neuropathological conditions. The importance of balancing the promise of this transplantation candidate in the light of these emerging properties is crucial as the potential application in the clinical setting approaches. The first of three sections in this review discusses (A) the pathophysiology of spinal cord injury (SCI) and how stem cell therapies can positively alter the pathology in experimental SCI. Part B summarizes (i) the available technologies to deliver transgenes to generate iPSCs and (ii) recent data comparing iPSCs to ESCs in terms of characteristics and molecular composition. Lastly, in (C) we evaluate iPSC-based therapies as a candidate to treat SCI on the basis of their neurite induction capability compared to embryonic stem cells and provide a summary of available in vivo data of iPSCs used in SCI and other disease models.

Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat

“…6 By immunohistochemical staining analysis, the protein levels of BDNF and VEGF were significantly higher in Ngn2-ADSCs group and ADSCs group compared to those in control group (a, b, *P \ 0.05); and the protein levels in Ngn2-ADSCs group were significantly higher than those in ADSCs group (a, b, # P \ 0.05) Cell Mol Neurobiol Astrocyte proliferation is a major contributor to glial scar formation after SCI (White and Jakeman 2008). Scar tissue is now widely accepted to be both a physical as well as a chemical barrier for axonal growth and regeneration, at least in experimental SCI (Kramer et al 2013). Our study indicated that GFAP expression at the injury site in the Ngn2-ADSCs group was decreased compared with that in the other two groups on day 14 after transplantation.…”

Recent technological updates and clinical applications of induced pluripotent stem cells

“…Researchers would then be able to simulate the conditions caused by aberrant genes of patient-specific iPSCs in a dish or in a tube. On the other hand, the expense incurred by the generation of certain genetic mutations in cell lines or animal models can be an economical roadblock to large-scale drug development and disease modeling [2,63]. From this point of view, the generation of patient-specific iPSCs often costs less than the generation of animal disease models or genetically engineered animals.…”

Comparison of Capability of Human Bone Marrow Mesenchymal Stem Cells and Endometrial Stem Cells to Differentiate into Motor Neurons on Electrospun Poly(ε-caprolactone) Scaffold

“…The development of cell-based therapies aimed at repairing neuropathological and neurodegenerative conditions of the CNS have been utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages [6]. The use and popularity of each cell type are guided by a number of factors including neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cell myelination capability [6].…”

“…The development of cell-based therapies aimed at repairing neuropathological and neurodegenerative conditions of the CNS have been utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages [6]. The use and popularity of each cell type are guided by a number of factors including neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cell myelination capability [6]. Various stem cells, such as multipotent adult progenitor, mesenchymal, haemopoietic, umbilical cord blood (UCB), and embryonic stem cells (ESCs), have the potency to differentiate into the neural cells [7][8][9][10][11][12][13].…”