MTS Spark Waves® – a new regenerative therapy for paraplegia
Extracorporeal shock wave therapy (ESWT) is widely used in clinical practice. In addition to its original use in kidney stone disintegration, shock waves are now used for the treatment of a variety of regenerative indications. Mechanotransduction stimulates the body’s biological healing processes at the cellular level. In areas of wound healing, orthopaedics or erectile dysfunction, very good, well-founded treatment successes are achieved.
The molecular mechanism of action is based on the activation of cellular signaling molecules which stimulate the blood circulation (vascularisation) of the affected tissue. 1–7 Shock waves induce the proliferation and migration of cells, have anti-apoptotic, anti-inflammatory as well as analgesic effects. 1,2,8–20
Benefits of Spark Wave Therapy® in neuronal regeneration:
Studies have shown that ESWT has a positive effect on the expression of important growth factors such as BNDF (brain-derived neurotrophic factor), BMP (bone morphogenetic protein) and TGF-β (transforming growth factor), FGF-2 (fibroblast growth factor), IGF-1 (insulin growth factor) and PCNA (proliferating cell nuclear antigen). 21–26 In particular, the proangiogenic factor VEGF (the vascular endothelial growth factor) and its associated receptor VEGF-R2 are upregulated. 27–29 Studies indicate that VEGF exerts a neuroprotective effect and prevents secondary damage to neural tissue after spinal cord injury. 29,30 These studies showed that VEGF stimulates endothelial and neural cells, acts neurotropically and neuroprotectively, and promotes neural cell division. Blocking of the VEGF signalling pathway led to cell death and after spinal cord injury, expression of VEGF decreased, which was associated with a worsening of the pathological condition. 29 Increased expression of VEGF and an improvement in tissue vascularization by ESWT therefore represent a promising treatment approach.
Recent research results in the rat model show that ESWT stimulates VEGF expression and angiogenesis after spinal cord injury and leads to an improved restoration of motor and sensory function.29,31–33 In particular, it has been shown that the use of low-energy shock waves does not lead to nerve tissue damage. 29
Spark Wave Therapy stimulates the expression of VEGF, reduces secondary damage to injured nerve tissue and improves the restoration of motor function. Therefore, it would be desirable to use this innovative therapeutic strategy in everyday clinical practice to accompany the treatment of spinal cord injuries.
- Wang, C.-J., Wu, R.-W. & Yang, Y.-J. Treatment of diabetic foot ulcers: A comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy. Diabetes Res. Clin. Pract. 92, 187–193 (2011).
- Mittermayr, R. et al. Extracorporeal Shock Wave Therapy (ESWT) Minimizes Ischemic Tissue Necrosis Irrespective of Application Time and Promotes Tissue Revascularization by Stimulating Angiogenesis. Ann. Surg. 253, 1024–1032 (2011).
- Kisch, T. et al. Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation. J. Tissue Viability 24, 140–145 (2015).
- Kuo, Y. R., Wang, C. T., Wang, F. S., Chiang, Y. C. & Wang, C. J. Extracorporeal shock-wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ-induced diabetes. Wound Repair Regen. 17, 522–530 (2009).
- Kisch, T. et al. Repetitive shock wave therapy improves muscular microcirculation. J. Surg. Res. 201, 440–445 (2016).
- Ellah, M. A. et al. Changes of renal blood flow after ESWL: Assessment by ASL MR imaging, contrast enhanced MR imaging, and renal resistive index. Eur. J. Radiol. 76, 124–128 (2010).
- Vardi, Y., Appel, B., Jacob, G., Massarwi, O. & Gruenwald, I. Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction. Eur. Urol. 58, 243–248 (2010).
- Kuo, Y. R. et al. Extracorporeal shock wave treatment modulates skin fibroblast recruitment and leukocyte infiltration for enhancing extended skin-flap survival. Wound Repair Regen. 17, 80–87 (2009).
- Davis, T. A. et al. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury. Int Wound J 6, 11–21 (2009).
- Hausdorf, J., Schmitz, C., Averbeck, B. & Maier, M. [Molecular basis for pain mediating properties of extracorporeal shock waves]. Schmerz 18, 492–497 (2004).
- Fojecki, G. L., Tiessen, S. & Osther, P. J. Extracorporeal shock wave therapy (ESWT) in urology: a systematic review of outcome in Peyronie’s disease, erectile dysfunction and chronic pelvic pain. World J Urol (2016).
- Cho, Y. S. et al. Effect of extracorporeal shock wave therapy on scar pain in burn patients: A prospective, randomized, single-blind, placebo-controlled study. Medicine (Baltimore). 95, e4575 (2016).
- Cai, Z. et al. Effects of Shock Waves on Expression of IL-6, IL-8, MCP-1, and TNF-alpha Expression by Human Periodontal Ligament Fibroblasts: An In Vitro Study. Med. Sci. Monit. 22, 914–921 (2016).
- Zhao, Z. et al. Extracorporeal shock-wave therapy reduces progression of knee osteoarthritis in rabbits by reducing nitric oxide level and chondrocyte apoptosis. Arch. Orthop. Trauma Surg. 132, 1547–1553 (2012).
- Raabe, O. et al. Effect of extracorporeal shock wave on proliferation and differentiation of equine adipose tissue-derived mesenchymal stem cells in vitro. Am. J. Stem Cells 2, 62–73 (2013).
- Lin, G. et al. In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy. J. Sex. Med. 1–9 (2017). doi:10.1016/j.jsxm.2017.02.004
- Weihs, A. M. et al. Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation. J. Biol. Chem. 289, 27090–104 (2014).
- Sukubo, N. G., Tibalt, E., Respizzi, S., Locati, M. & d’Agostino, M. C. Effect of shock waves on macrophages: A possible role in tissue regeneration and remodeling. Int. J. Surg. 24, 124–130 (2015).
- Holfeld, J. et al. Shockwave therapy differentially stimulates endothelial cells: implications on the control of inflammation via toll-Like receptor 3. Inflammation 37, 65–70 (2014).
- Stojadinovic, A. et al. Angiogenic response to extracorporeal shock wave treatment in murine skin isografts. Angiogenesis 11, 369–380 (2008).
- Wang, B. et al. Low-intensity extracorporeal shock wave therapy enhances brain-derived neurotrophic factor expression through PERK/ATF4 signaling pathway. Int. J. Mol. Sci. 18, (2017).
- Frairia, R. & Berta, L. Biological effects of extracorporeal shock waves on fibroblasts. A review. Muscles. Ligaments Tendons J. 1, 138–47 (2011).
- Hausdorf, J. et al. Stimulation of bone growth factor synthesis in human osteoblasts and fibroblasts after extracorporeal shock wave application. Arch. Orthop. Trauma Surg. 131, 303–309 (2011).
- Wang, C. J. et al. The effects of shockwave on bone healing and systemic concentrations of nitric oxide (NO), TGF-β1, VEGF and BMP-2 in long bone non-unions. Nitric Oxide – Biol. Chem. 20, 298–303 (2009).
- Chen, Y. J. et al. Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-??1 and IGF-I expression. J. Orthop. Res. 22, 854–861 (2004).
- Wang, C.-J., Wang, F.-S. & Yang, K. D. Biological effects of extracorporeal shockwave in bone healing: a study in rabbits. Arch. Orthop. Trauma Surg. 128, 879–884 (2008).
- Yin, T.-C., Wang, C.-J., Yang, K. D., Wang, F.-S. & Sun, Y.-C. Shockwaves enhance the osteogenetic gene expression in marrow stromal cells from hips with osteonecrosis. Chang Gung Med. J. 34, 367–74 (2011).
- Yamaya, S. et al. Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury. J. Neurosurg. 121, 1514–1525 (2014).
- Wang, L., Jiang, Y., Jiang, Z. & Han, L. Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function. Neuropsychiatr. Dis. Treat. Volume 12, 2189–2198 (2016).
- Basso, D. M. Behavioral testing after spinal cord injury: congruities, complexities, and controversies. J. Neurotrauma 21, 395–404 (2004).
- Yamaya, S. et al. Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury. J. Neurosurg. (2014). doi:10.3171/2014.8.JNS132562
- Yahata, K. et al. Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury. J. Neurosurg. Spine (2016). doi:10.3171/2016.4.SPINE15923
- Lee, J. H. & Kim, S. G. Effects of extracorporeal shock wave therapy on functional recovery and neurotrophin-3 expression in the spinal cord after crushed sciatic nerve injury in rats. Ultrasound Med. Biol. (2015). doi:10.1016/j.ultrasmedbio.2014.10.015