Endogenous stem cell proliferation after central nervous system injury: alternative therapeutic options

Abstract

<jats:p>The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.</jats:p>

Stem cell biology and its therapeutic applications in the setting of spinal cord injury

“…The Shh protein, which is critical in oligodendroglial development and developmental neurogenesis, dramatically increases the number of neuronal progenitor cells in N. C. Bambakidis et al the spinal cord. 3,4 A similar phenomenon is observed in rats with a contusion injury to the spinal cord. After oligodendrocytic precursors have been transplanted, markedly reduced demyelination and increased conduction velocity are observed across lesions.…”

“…5 and 6). 2,3 The availability of small-molecule analogs to the Shh pathway that may be administered intravenously allows these experimental findings to be reproduced while obviating the need for direct injection into the injured spinal cord. In recent experiments involving contusive SCI, these agents upregulated endogenous cell populations; further work is ongoing.…”

“…24 Rests are also found in the ependymal lining of the spinal cord, where they actively divide in the presence of an injury. 3,9,13,18 Neuroregeneration After secondary injury, the potential for neuroregenerative therapies begins. However, the presence of the astrocytic scar is the major impediment to the restoration of functional electrochemical synapses and axonal recovery.…”

Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish

“…There are no fully restorative therapies known for mammalian spinal cord injury (Thuret et al, 2006; Lu et al, 2004; Buchli et al, 2007; Cafferty et al, 2008; Bunge, 2008; Fawcett, 2009). Over the past few decades, the discovery of endogenous multipotent and pluripotent stem cell populations in specialized niches of the adult central nervous system that continually give rise to differentiating neural cells (Horner et al, 2000; Weiss et al, 1996; Shihabuddin, 2008) has led to advances in stem cell therapies for spinal cord injury (Agrawal and Schaffer, 2005; Bambakidis et al, 2005; Conti and Cattaneo, 2008). However, little is known about the mechanisms of activation and subsequent neural differentiation of endogenous neural stem cells by which we can gain further insights into the optimization of regenerative neurogenesis in mammals.…”

Long-Term Complications of Chronic Traumatic Paraplegia: An Experience from Pakistan

“…Spinal cord injuries cause immense economic, social, and psychological burden both on the families as well as on the society. Its annual cost in the USA is 9.7 billion US dollars per year [3][4]. 1 The available therapies for spinal cord injuries are either limited or ineffective.…”