Induced pluripotent stem cell technology for spinal cord injury: a promising alternative therapy

Abstract

Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients. There are currently a large number of therapeutic strategies for treating spinal cord injury, which range from pharmacological and surgical methods to cell therapy and rehabilitation training. All of these strategies have positive effects in the course of spinal cord injury treatment. This review mainly discusses the problems regarding stem cell therapy for spinal cord injury, including the characteristics and action modes of all relevant cell types. Induced pluripotent stem cells, which represent a special kind of stem cell population, have gained impetus in cell therapy development because of a range of advantages. Induced pluripotent stem cells can be developed into the precursor cells of each neural cell type at the site of spinal cord injury, and have great potential for application in spinal cord injury therapy.

Keywords: axon regeneration; cell therapy; functional recovery; induced pluripotent stem cell; mesenchymal stem cell; neural cells; neural precursor cell; neural stem cell; remyelination; spinal cord injury; stem cells.

Figure 1

Adverse niche for regeneration and the roles of transplanted cells in SCI. This figure depicts the phenomenon of vascular damage, ischemia, tissue edema, and neuron interruption after SCI. It also shows subsequent second injury, including inflammatory factor/cell aggregation, demyelination, and glial scar and cystic cavity formation. The grafted NSCs/NPCs differentiate into oligodendrocytes, astrocytes, and neurons to play roles in remyelination, the release of neuronal factors, and neural circuit reconstruction, respectively. The grafted MSCs play anti-inflammatory/apoptotic roles, and both transplanted MSCs and OECs provide nutritional support for axonal regeneration. BDNF: Brain-derived neurotrophic factor; bFGF: basic fibroblast growth factor; CSPG: chondroitin sulfate proteoglycan; HGF: hepatocyte growth factor; MSC: mesenchymal stem cell; NGF: neural growth factor; NSC/NPC: neural stem/precursor cell; OEC: olfactory ensheathing cell; OPC; oligodendrocyte precursor cell; SCI: spinal cord injury; VEGF: vascular endothelial growth factor.

Figure 2

The development process of cell-based SCI therapies. This figure shows many of the cells covered in the development process of cell-based therapies for SCI. From 1986 to 2006, Schwann cells, OECs, ESCs, NSCs, and MSCs have all been explored for SCI treatment and received more or less satisfactory outcomes. From 2006 to 2019, with the rise and development of IPS technology and IPS-derived cell types have been welcomed. CNS: Central nervous system; IPS: induced pluripotent stem cell; ESC: embryonic stem cell; MSC: mesenchymal stem cell; NSC/NPC: neural stem/precursor cell; OEC: olfactory ensheathing cell; SCI: spinal cord injury.

Figure 3

Application of IPS technology for SCI therapy using autologous somatic cells. During IPS-based SCI therapy, somatic cell collection, IPS formation, cell differentiation, and autologous cell transplantation are performed in order. IPS: Induced pluripotent stem cell; SCI: spinal cord injury.