Spinal Cord Injury
Spinal cord injury (SCI) is a major medical problem worldwide. SCI is a devastating injury which involves an initial mechanical damage followed by a series of cellular and molecular secondary events resulting in the progressive destruction of spinal cord tissue. Neuropathic pain (NP) is one of the most debilitating sequelae of neurotrauma and remains an unmet clinical need for at least 40% of patients with SCI. Methylprednisolone is the only FDA approved drug that is currently available to limit the extent of SCI in the acute settings but it does nothing for prevention or mitigation of subsequent neuropathic pain following SCI. Despite decades of extensive research in this area, no clinically effective therapies exist to modulate neuropathic pain and facilitate functional recovery after spinal cord injury. SCI results in a multitude of changes affecting several different cell types, leading to a complex pathological picture. Most research findings to date suggest that no single therapy will be sufficient to overcome the myriad of biological cascade initiated after SCI. Effective treatments of SCI require a multifaceted approach using a combination of different methodologies and therapeutic approaches over different time to address many of the devastating issues besides functional impairment such as chronic pain associated with SCI.
Source: Figure 6A from Veeravalli et al., Neurobiology of disease 2009; 36: 200
Our current research utilizes two cutting edge approaches, stem cell transplantation and gene silencing. A variety of different stem cell types have been evaluated in animal models and humans with SCI. Previous studies have reported that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) promotes neural repair after SCI, even when administered 5 days after injury. Transplanted hUCB-MSCs differentiate into various neural cells and induce motor function improvement in SCI rat models. In concert with these findings, we also have recently reported that hUCB-MSCs improved the locomotor recovery of spinal cord injured rats while regulating the expression of several genes related to apoptosis, axon outgrowth and myelin degradation. However, more detail experiments are needed to delineate the mechanism of how hUCB-MSCs modulate NP and functional improvement after SCI.
- Chelluboina B, Dinh DH, Veeravalli KK. Transdifferentiation of differentiated stem cells contributes to remyelination. Stem Cell Research & Therapy 2015; 6: 191.
- Dasari VR, Veeravalli KK, Dinh DH. Mesenchymal stem cells in the treatment of spinal cord injuries: A review. World Journal of Stem Cells 2014; 6: 120-133.
- Veeravalli KK, Dasari VR, Rao JS. Regulation of proteases after spinal cord injury. J Neurotrauma 2012; 29: 1-12
- Dasari VR, Veeravalli KK, Fassett D, Rao JS, Dinh DH. Mesenchymal stem cell therapy for apoptosis after spinal cord injury. Advanced Understanding of Neurodegenerative diseases ISBN 978-953-307-529-7, Intech (Publisher), 2011; 365-394.
- Kotipatruni RR, Dasari VR, Veeravalli KK, Dinh DH, Fassett D, Rao JS. p53- and Bax-mediated apoptosis in injured rat spinal cord. Neurochemical Research 2011; 36: 2063-2074.
- Veeravalli KK, Dasari VR, Fassett D, Dinh DH, Rao JS. Human umbilical cord blood derived mesenchymal stem cells upregulate myelin basic protein in shiverer mice. Stem Cells and Development 2011; 20: 881-891.
- Veeravalli KK, Dasari VR, Tsung AJ, Dinh DH, Gujrati M, Fassett D, Rao JS. Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury. Neurobiology of Disease 2009; 36: 200-212.
- Dasari VR, Veeravalli KK, Tsung AJ, Gondi CS, Gujrati M, Dinh DH, Rao JS. Neuronal apoptosis is inhibited by cord blood stem cells after spinal cord injury. J Neurotrauma 2009; 26: 2057-2069.
- Veeravalli KK, Dasari VR, Tsung AJ, Dinh DH, Gujrati M, Fassett D, Rao JS. Stem Cells downregulate the elevated levels of tissue plasminogen activator in rats after spinal cord injury. Neurochemical Research 2009; 34: 1183-1194.
- Dasari VR, Veeravalli KK, Saving KL, Gujrati M, Fassett D, Klopfenstein JD, Dinh DH, Rao JS. Neuroprotection by cord blood stem cells against glutamate-induced apoptosis is mediated by Akt pathway. Neurobiology of Disease 2008; 32(3): 486-498.