|Year : 2022 | Volume
| Issue : 1 | Page : 3-8
Potential applications of low-intensity extracorporeal shock-wave therapy in urological diseases via activation of tissue resident stem cells
Bohan Wang1, Amanda B Reed-Maldonado2, Kim Ly3, Guiting Lin3, Tom F Lue3
1 Department of Urology, School of Medicine, Knuppe Molecular Urology Laboratory, University of California, San Francisco, CA, USA; Department of Urology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, China
2 Department of Urology, School of Medicine, Knuppe Molecular Urology Laboratory, University of California, San Francisco, CA; Department of Urology, Tripler Army Medical Center, Honolulu, HI, USA
3 Department of Urology, School of Medicine, Knuppe Molecular Urology Laboratory, University of California, San Francisco, CA, USA
|Date of Submission||06-Apr-2021|
|Date of Decision||19-Aug-2021|
|Date of Acceptance||31-Aug-2021|
|Date of Web Publication||31-Jan-2022|
Prof. Tom F Lue
Department of Urology, University of California, San Francisco, 400 Parnassus Ave., Ste A-633, San Francisco, CA 94143-0738
Source of Support: None, Conflict of Interest: None
For many years, low-intensity extracorporeal shock-wave therapy (Li-ESWT) has been clinically applied as a noninvasive therapeutic method, for urological diseases. The major corresponding biological molecular mechanisms of Li-ESWT are to induce stem cell differentiation, neural regeneration, and angiogenesis. This narrative review aims to present an overview of the potential utility of Li-ESWT and its effects on stem cell therapies. Recent studies have also shown that the combination treatment of Li-ESWT and stem cell therapies can be a new option for the treatment of erectile dysfunction (ED), urinary incontinence, bladder dysfunction, and other diseases. The potential contributions of Li-ESWT on stem cell therapies for these diseases are studied, highlighting the influence of Li-ESWT on proliferation, viability, and differentiation capacity of certain stem cells. The potential mechanisms, including the increased expression of vascular endothelial growth factor, chemokine CXC motif ligand 5, and transforming growth factor-β1 are described herein. Li-ESWT can also activate many cellular signaling pathways. The combination of Li-ESWT and stem cell therapies is a promising strategy for urological diseases. However, a much greater understanding of the mechanisms by which Li-ESWT enhances the efficacy of stem cell therapy is still needed before this combined treatment can be recommended for large-scale clinical application.
Keywords: Activation, bladder dysfunction, erectile dysfunction, low-intensity extracorporeal shock wave therapy, mechanism, stem/progenitor cells, urinary incontinence
|How to cite this article:|
Wang B, Reed-Maldonado AB, Ly K, Lin G, Lue TF. Potential applications of low-intensity extracorporeal shock-wave therapy in urological diseases via activation of tissue resident stem cells. Urol Sci 2022;33:3-8
|How to cite this URL:|
Wang B, Reed-Maldonado AB, Ly K, Lin G, Lue TF. Potential applications of low-intensity extracorporeal shock-wave therapy in urological diseases via activation of tissue resident stem cells. Urol Sci [serial online] 2022 [cited 2022 Aug 13];33:3-8. Available from: https://www.e-urol-sci.com/text.asp?2022/33/1/3/336916
| Introduction|| |
Low-intensity extracorporeal shock-wave therapy (Li-ESWT) is a form of energy transfer that is <0.2 mJ/mm2 than the ESWT employed for lithotripsy and nephrolithiasis treatment. This lower intensity, with the appropriate dosage of energy transfer, is thought to induce beneficial effects in human tissues. Li-ESWT has been used to treat ischemic heart disease, musculoskeletal disorders, erectile dysfunction (ED), and urinary incontinence (UI) for many years. The mechanisms underlying Li-ESWT include tissue regeneration, angiogenesis, reduction of inflammation, and stem cell activation and recruitment.
Stem cell therapies have also been studied for several years with the goal of replacing lost or damaged cells. In recent years, different approaches for stem cell acquisition included procurement from multiple sources and for delivery included seeding of stem cell lysate and stem cells on tissue. However, the limitations of exogenous stem cells in therapeutic applications have become obvious. It has been reported that migration of implanted stem cells enhanced tumor growth. Therefore, activation of endogenous stem cells by Li-ESWT offers an ideal therapy and avoids the potential complications of traditional stem cell therapies. In this review, we summarize the interactions between Li-ESWT and stem cell therapies.
| Low-intensity Extracorporeal Shock-Wave Therapy and Erectile Dysfunction|| |
Over the past decade, Li-ESWT has evolved from an experimental therapy to an exciting potential treatment option for ED. The use of Li-ESWT in the treatment of ED was first reported in 2010, in a study which assessed the efficacy of Li-ESWT in patients with ED with a 6-month follow-up. Since then, an increasing amount of evidence has suggested that Li-ESWT is an effective approach for ED. Specifically, clinical research showed improvement in IIEF-EF score and a high rate of conversion of nonresponders to phosphodiesterase type-5 inhibitors after the application of Li-ESWT., Animal studies have also revealed that Li-ESWT could promote the regeneration of endothelial cells and smooth muscle, which ultimately improves erectile function., In addition, studies have demonstrated that Li-ESWT could partially ameliorate diabetes mellitus-associated ED by promoting the regeneration of neuronal nitric oxide synthase (nNOS)-positive nerves, endothelium, and smooth muscle in the penis. These beneficial effects appear to be mediated by the recruitment of endogenous mesenchymal stem cells (MSCs). Recently, combination therapies of stem cells with drugs, herbs, and Li-ESWT have shown better results compared with single treatment. The combination of Li-ESWT with stem cells has attracted much attention because Li-ESWT is a noninvasive technique with a major advantage of possible restoration of natural penile erections. Moreover, Li-ESWT is an ED treatment with the potential for an actual cure.
Lin et al. confirmed that Li-ESWT increased EdU + cells within the subtunical spaces in penile erectile tissue. Li-ESWT also stimulated cell proliferation of endothelial and Schwann cells through the Erk1/2 pathway. In another study, Li-ESWT was shown to restore penile smooth muscle and endothelium content and to reduce lipid accumulation. Collectively, these studies suggest that the mechanism underlying Li-ESWT appears to be the activation of stem/progenitor cells in situ, which prompts cellular proliferation and accelerates penile tissue regeneration.
Interestingly, Li-ESWT was also shown to improve the survival of transplanted stem cells. Shan et al. indicated that the combination of Li-ESWT with bone marrow MSCs (BMSCs) transplantation improved erectile function in diabetic rats more effectively than Li-ESWT or BMSC transplantation performed alone. It is postulated that Li-ESWT increases the expression of stromal cell-derived factor-1 (SDF-1), which inhibits the migration of BMSCs and facilitates the retention of BMSCs in the cavernous body. Moreover, Li-ESWT enhanced revascularization in the cavernous body, which may create a supportive environment in which the transplanted BMSCs thrive. The application of adipose-derived stem cells (ADSCs) along with Li-ESWT could improve ED by enhancing the expression of alpha-smooth muscle actin (α-SMA), nNOS, and Von Willebrand factor in the corpus cavernosum of rats with ED. In a rat model of post-prostatectomy ED, the combination of ADSCs and Li-ESWT showed enhanced recovery of erectile function. The results demonstrated that ADSCs enhance nerve regeneration by increasing β-III tubulin and nNOS expression. In addition, Li-ESWT is capable of significantly upregulating the expression of vascular endothelial growth factor (VEGF) and inducing neovascularization on the cavernous nerve as well as improving vascular supply to the penis and decreasing apoptosis of cells in the corpus cavernosum. Furthermore, combination therapy with Li-ESWT and MSCs was confirmed to be more effective for ED than either treatment alone. In summary, previous studies proved that the combination of Li-ESWT and stem cells had a greater impact on ED than stem cells therapy or Li-ESWT treatment alone; however, the interactions between stem cells and Li-ESWT, as well as the potential side effects of combination therapies, remain poorly defined. According to early studies, Li-ESWT contributes to the proliferation, differentiation, and paracrine effects of stem cells., Jeon et al. also investigated the mechanism of combined Li-ESWT and MSCs therapy in a rat model of diabetic ED. They found that the quantity of MSCs could be significantly increased by Li-ESWT treatment. Furthermore, Li-ESWT could induce MSCs to express more VEGF in vivo and in vitro, which contributed to autophagy by triggering the PI3K/AKT/mTOR and NO/cGMP signaling pathways. In addition, Li-ESWT could be an effective tool for accelerating the production of and increasing the concentration of VEGF during the application of stem cell therapy. It has been demonstrated that Li-ESWT could promote angiogenesis and proliferation by activating penile progenitor cells in the diabetes mellitus-associated ED (DMED) microenvironment, which was consistent with the results obtained in animals. Li-ESWT promoted the expression of SDF-1 and platelet endothelial cell adhesion molecule-1 in DMED rats, which can attract stem cells to the corpus cavernosum.
| Low-intensity Extracorporeal Shock-Wave Therapy and Urinary Incontinence|| |
Both clinical and preclinical studies have demonstrated that Li-ESWT is a potential noninvasive therapy for UI owing to its capability to stimulate striated muscle growth and tissue regeneration.,, The striated urethral sphincter plays a crucial role in continence for both men and women. Striated muscle, also known as skeletal muscle, is composed of multinucleated contractile muscle cells called myofibers. During development, myofibers are formed by fusion of mesoderm progenitors called myoblasts, which originate from satellite cells. Satellite cells, also known as muscle stem cells, play an essential role in muscle regeneration and functional recovery by virtue of their intrinsic ability to generate a large number of new myofibers. One important finding demonstrated that Li-ESWT induces muscle regeneration by stimulating satellite cell myogenic differentiation. Thus, Li-ESWT could increase the number of progenitor cells in the urethra and enhance the recruitment of MSC with increased expression of VEGF.,,
| Low-intensity Extracorporeal Shock-Wave Therapy and Bladder Dysfunction|| |
Recent research demonstrated that stem cell therapy for bladder dysfunction (BD) could be enhanced by Li-ESWT. BD is considered a suitable urologic disease for stem cell therapy because its underlying pathophysiology involves neuropathy and vasculopathy. However, previous study found that 40%–60% of samples from a BD rat model showed no response to ADSCs treatment. Nevertheless, the therapeutic effect of ADSCs injection could be improved by Li-ESWT. Notably, only 52.3% of BD rats had normal voiding function after ADSCs injection, whereas up to 75.0% showed a normal voiding pattern after combined application of Li-ESWT with ADSCs. These results demonstrate that Li-ESWT-treated ADSCs had the best efficacy in treating diabetic BD due to secretion of VEGF and nerve growth factor (NGF), which enhance vascular and neural regeneration.
The same authors also verified Li-ESWT to be a promising trigger for the secretion of cytokine and growth factors, such as NGF and VEGF, by ADSCs. This study improved innervation and vascularization of the bladder in vivo. The improvement of diabetic BD may be due to the recruitment of endogenous stem cells to the bladder by Li-ESWT.
| Low-intensity Extracorporeal Shock-Wave Therapy and Other Diseases|| |
Li-ESWT has been considered a noninvasive, effective, versatile, and repeatable therapy for the treatment of several musculoskeletal diseases and for some pathological conditions in which regenerative effects are desirable, particularly if other noninvasive or conservative therapies have failed. Moreover, experimental and clinical studies demonstrate that the efficacy of ESWT in accelerating tissue repair and regeneration in various wounds.,, In a tissue ischemia model, Li-ESWT mobilized endothelial progenitor cells to the target organ to facilitate angiogenesis.
Li-ESWT has been known to promote tissue regeneration after sports injuries and enhances blood flow in muscle tissue shortly after the application. The biological responses triggered by Li-ESWT include the recruitment of MSCs, stimulation of cell proliferation and differentiation, and anti-inflammatory effects. These are considered important therapeutic effects of Li-ESWT for soft-tissue wound healing.
Li-ESWT has been reported to enhance the proliferation and function of BMSCs. The Li-ESWT activated BMSCs secrete more VEGF and chemokine CXC motif ligand 5 than untreated BMSCs. The treated BMSCs also demonstrated a higher capacity to promote angiogenesis and nerve regeneration in vitro in a high-glucose medium. The authors suggested that the transplantation of Li-ESWT-treated BMSCs might promote tissue regeneration in diabetes. In a rat model of chronic hind limb ischemia, combined Li-ESWT and endothelial progenitor cells (EPCs) treatment significantly improved blood flow recovery. The improved efficacy is believed to be a result of increased tissue expression of chemoattractant factors such as SDF-1 and VEGF. These factors are crucial for the recruitment of circulating EPCs during acute ischemia.
In vitro research has also demonstrated that Li-ESWT facilitates the proliferation and differentiation of neural stem cells, which play a pivotal role in the repair of brain function in the diseases of the central nervous system. Furthermore, Li-ESWT reduces the risk of skin and tissue fibrosis. Rinella et al. studied the effects of Li-ESWT in modulating the differentiation of human ADSCs toward myofibroblasts. The results show that Li-ESWT downregulated the expression of the myofibroblast marker α-SMA and the extracellular matrix protein type I collagen. Moreover, Li-ESWT reduced the expression of integrin alpha 11, a major collagen receptor in fibroblastic cells that is involved in the differentiation of myofibroblast.
Li-ESWT is also a useful noninvasive therapy for human bone fracture repair.,, In bone, Li-ESWT promotes the expression of bone morphogenetic proteins (BMP), collagen type |, and alkaline phosphatase, which play an important role in bone development and fracture healing. Early research reported that Li-ESWT induced satisfactory healing effects of segmental bone defects through the stimulation of MSC recruitment and differentiation into bone-forming cells by increasing the expression of transforming growth factor (TGF)-β1 and VEGF-A mRNA. Another clinical study reported that systemic concentrations of NO, TGF-β1, VEGF, and BMP-2 increased dramatically after 1 month of ESWT in patients with long bone nonunions. The satisfactory results verified the positive therapeutic effect of ESWT for bone fractures. In addition, ESWT had positive effects on osteoblast proliferation by upregulating the expression of genes that participate in skeletal development and osteoblastic lineage differentiation.
| Cellular Signaling Pathways Involved in Li-ESWT-Induced Stem Cell Activation|| |
Li-ESWT regulates cellular signaling pathways, thereby affecting the transcription and modification of intracellular proteins. Specific cellular processes/molecules modulated by Li-ESWT include protein kinase RNA-like endoplasmic reticulum kinase/activated transcription factor (PERK/ATF), Wnt/β-catenin, and extracellular-signal-regulated kinase (ERK).
| Protein Kinase RNA-Like Endoplasmic Reticulum Kinase/Activated Transcription Factor Signaling Pathway|| |
PERK is an important pathway responsible for the attenuation of the overloaded misfolded proteins, consequently attenuating endoplasmic reticulum stress. PERK phosphorylation activates the α subunit of eukaryotic initiation factor 2, which subsequently allows the translation of UPR-dependent genes, such as ATF4.
Recently, studies have also shown that Li-ESWT activates the PERK/ATF4 pathway to stimulate myotube formation in cultured myoblasts and to increase the expression of brain-derived neurotrophic factor in cultured Schwann cells. These studies elucidate some of the mechanobiological pathways responsible for the clinical improvements observed after Li-ESWT.
| Wnt/β-Catenin Cellular Signaling Pathway|| |
The Wnt signaling pathway, a highly conserved sequence across taxa, is a complex network of protein action relevant for embryonic development, neoplasia, and normal physiological processes of adult animals.
The Wnt/β-catenin and Notch pathway also appear to play important roles in the long-term efficacy of Li-ESWT. In one study, Li-ESWT induced penile stem/progenitor cell differentiation into smooth muscle cells through the Wnt/β-catenin signaling pathway in a time- and dosage-dependent manner.
| ERK Pathway|| |
Mitogen-activated protein kinases (MAPKs) form major cell-proliferation signaling pathways from the cell surface to the nucleus. There are three major subfamilies of MAPK: ERK, c-Jun N-terminal or stress-activated protein kinases, and MAPK14. MAPK signaling pathways are known to play a central role in the proliferation, differentiation, apoptosis, inflammation, and development of cells. The ERK MAPK is one of the most important pathway for cell proliferation.
Li-ESWT triggers the release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo through downstream ERK ½ signaling.
| Perspectives|| |
Combined therapy between Li-ESWT and stem cells may have added beneficial effects in urological diseases, such as ED, UI, and BD. Studies show that Li-ESWT alone can activate local endogenous stem cells as well as promote the proliferation, differentiation, and migration of stem cells. The combination of BMSCs and Li-ESWT shows significant potential in rehabilitative and orthopedics medicine (tendon pathologies, bone healing, and ischemic bone diseases), dermatology (ulcers, wound healing disturbances, and painful scars), neurology (spastic hypertonia and related syndromes), and ischemic heart diseases. Li-ESWT alone has been considered an effective, safe, versatile, repeatable, and noninvasive therapy. The combination of Li-ESWT and stem cells is a promising therapy in the field of regenerative medicine and tissue engineering. However, the mechanisms involved are not yet fully understood and additional research is warranted from basic science research to large-scale clinical applications before the application of combination therapy.
Financial support and sponsorship
This publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number 1R01DK124609. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflicts of interest
Prof. Tom F. Lue, an editorial board member at Urological Science, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
| References|| |
Abe Y, Ito K, Hao K, Shindo T, Ogata T, Kagaya Y, et al
. Extracorporeal low-energy shock-wave therapy exerts anti-inflammatory effects in a rat model of acute myocardial infarction. Circ J 2014;78:2915-25.
Al-Abbad H, Simon JV. The effectiveness of extracorporeal shock wave therapy on chronic achilles tendinopathy: A systematic review. Foot Ankle Int 2013;34:33-41.
Gruenwald I, Appel B, Vardi Y. Low-intensity extracorporeal shock wave therapy –
A novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med 2012;9:259-64.
Long CY, Lin KL, Lee YC, Chuang SM, Lu JH, Wu BN, et al
. Therapeutic effects of low intensity extracorporeal low energy shock wave therapy (LiESWT) on stress urinary incontinence. Sci Rep 2020;10:5818.
Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, et al
. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med 2013;10:738-46.
Tepeköylü C, Wang FS, Kozaryn R, Albrecht-Schgoer K, Theurl M, Schaden W, et al
. Shock wave treatment induces angiogenesis and mobilizes endogenous CD31/CD34-positive endothelial cells in a hindlimb ischemia model: Implications for angiogenesis and vasculogenesis. J Thorac Cardiovasc Surg 2013;146:971-8.
Kuo YR, Wu WS, Hsieh YL, Wang FS, Wang CT, Chiang YC, et al
. Extracorporeal shock wave enhanced extended skin flap tissue survival via increase of topical blood perfusion and associated with suppression of tissue pro-inflammation. J Surg Res 2007;143:385-92.
Lin G, Reed-Maldonado AB, Wang B, Lee YC, Zhou J, Lu Z, et al. In situ
activation of penile progenitor cells with low-intensity extracorporeal shockwave therapy. J Sex Med 2017;14:493-501.
Strong TD, Gebska MA, Burnett AL, Champion HC, Bivalacqua TJ. Endothelium-specific gene and stem cell-based therapy for erectile dysfunction. Asian J Androl 2008;10:14-22.
Zhang H, Albersen M, Jin X, Lin G. Stem cells: Novel players in the treatment of erectile dysfunction. Asian J Androl 2012;14:145-55.
Lin G, Yang R, Banie L, Wang G, Ning H, Li LC, et al
. Effects of transplantation of adipose tissue-derived stem cells on prostate tumor. Prostate 2010;70:1066-73.
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 2010;58:243-8.
Campbell JD, Trock BJ, Oppenheim AR, Anusionwu I, Gor RA, Burnett AL. Meta-analysis of randomized controlled trials that assess the efficacy of low-intensity shockwave therapy for the treatment of erectile dysfunction. Ther Adv Urol 2019;11:1-13.
Palmieri A, Arcaniolo D, Palumbo F, Verze P, Liguori G, Mondaini N, et al
. Low intensity shockwave therapy in combination with phosphodiesterase-5 inhibitors is an effective and safe treatment option in patients with vasculogenic ED who are PDE5i non-responders: A multicenter single-arm clinical trial. Int J Impot Res 2021;33:634-640.
Liu J, Zhou F, Li GY, Wang L, Li HX, Bai GY, et al
. Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats. Int J Mol Sci 2013;14:10661-73.
Young Academic Urologists Men's Health Group, Fode M, Hatzichristodoulou G, Serefoglu EC, Verze P, Albersen M. Low-intensity shockwave therapy for erectile dysfunction: Is the evidence strong enough? Nat Rev Urol 2017;14:593-606.
Ruan Y, Zhou J, Kang N, Reed-Maldonado AB, Tamaddon A, Wang B, et al
. The effect of low-intensity extracorporeal shockwave therapy in an obesity-associated erectile dysfunction rat model. BJU Int 2018;122:133-42.
Shan HT, Zhang HB, Chen WT, Chen FZ, Wang T, Luo JT, et al
. Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats. Asian J Androl 2017;19:26-33.
] [Full text]
Jeon SH, Shrestha KR, Kim RY, Jung AR, Park YH, Kwon O, et al
. Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. Urology 2016;88:226.e1-9.
Zhu GQ, Jeon SH, Bae WJ, Choi SW, Jeong HC, Kim KS, et al
. Efficient promotion of autophagy and angiogenesis using mesenchymal stem cell therapy enhanced by the low-energy shock waves in the treatment of erectile dysfunction. Stem Cells Int 2018;2018:1302672.
Zhao Y, Wang J, Wang M, Sun P, Chen J, Jin X, et al
. Activation of bone marrow-derived mesenchymal stromal cells-a new mechanism of defocused low-energy shock wave in regenerative medicine. Cytotherapy 2013;15:1449-57.
Raabe O, Shell K, Goessl A, Crispens C, Delhasse Y, Eva A, 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 2013;2:62-73.
Jeon SH, Bae WJ, Zhu GQ, Tian W, Kwon EB, Kim GE, et al
. Combined treatment with extracorporeal shockwaves therapy and an herbal formulation for activation of penile progenitor cells and antioxidant activity in diabetic erectile dysfunction. Transl Androl Urol 2020;9:416-27.
Yip HK, Chang LT, Sun CK, Youssef AA, Sheu JJ, Wang CJ. Shock wave therapy applied to rat bone marrow-derived mononuclear cells enhances formation of cells stained positive for CD31 and vascular endothelial growth factor. Circ J 2008;72:150-6.
Zhang X, Ruan Y, Wu AK, Zaid U, Villalta JD, Wang G, et al
. Delayed treatment with low-intensity extracorporeal shock wave therapy in an irreversible rat model of stress urinary incontinence. Urology 2020;141:187.e1-7.
Wu AK, Zhang X, Wang J, Ning H, Zaid U, Villalta JD, et al
. Treatment of stress urinary incontinence with low-intensity extracorporeal shock wave therapy in a vaginal balloon dilation induced rat model. Transl Androl Urol 2018;7:S7-16.
Chargé SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev 2004;84:209-38.
Wang B, Zhou J, Banie L, Reed-Maldonado AB, Ning H, Lu Z, et al
. Low-intensity extracorporeal shock wave therapy promotes myogenesis through PERK/ATF4 pathway. Neurourol Urodyn 2018;37:699-707.
Zambon JP, Williams KJ, Bennington J, Badlani GH. Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients. Neurourol Urodyn 2019;38 Suppl 4:S76-83.
Shin JH, Ryu CM, Yu HY, Shin DM, Choo MS. Current and future directions of stem cell therapy for bladder dysfunction. Stem Cell Rev Rep 2020;16:82-93.
Zhang H, Qiu X, Shindel AW, Ning H, Ferretti L, Jin X, et al
. Adipose tissue-derived stem cells ameliorate diabetic bladder dysfunction in a type II diabetic rat model. Stem Cells Dev 2012;21:1391-400.
Zhang H, Zhao Y, Wang M, Song W, Sun P, Jin X. A promising therapeutic option for diabetic bladder dysfunction: Adipose tissue-derived stem cells pretreated by defocused low-energy shock wave. J Tissue Eng Regen Med 2019;13:986-96.
Jin Y, Xu L, Zhao Y, Wang M, Jin X, Zhang H. Endogenous stem cells were recruited by defocused low-energy shock wave in treating diabetic bladder dysfunction. Stem Cell Rev Rep 2017;13:287-98.
d'Agostino MC, Craig K, Tibalt E, Respizzi S. Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction. Int J Surg 2015;24:147-53.
Kuo YR, Wang CT, Wang FS, Chiang YC, Wang CJ. 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 2009;17:522-30.
Wang CJ, Cheng JH, Kuo YR, Schaden W, Mittermayr R. Extracorporeal shockwave therapy in diabetic foot ulcers. Int J Surg 2015;24:207-9.
Kisch T, Wuerfel W, Forstmeier V, Liodaki E, Stang FH, Knobloch K, et al
. Repetitive shock wave therapy improves muscular microcirculation. J Surg Res 2016;201:440-5.
Mittermayr R, Antonic V, Hartinger J, Kaufmann H, Redl H, Téot L, et al
. Extracorporeal shock wave therapy (ESWT) for wound healing: Technology, mechanisms, and clinical efficacy. Wound Repair Regen 2012;20:456-65.
Aicher A, Heeschen C, Sasaki K, Urbich C, Zeiher AM, Dimmeler S. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: A new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation 2006;114:2823-30.
Zhang J, Kang N, Yu X, Ma Y, Pang X. Radial extracorporeal shock wave therapy enhances the proliferation and differentiation of neural stem cells by Notch, PI3K/AKT, and Wnt/β-catenin signaling. Sci Rep 2017;7:15321.
Rinella L, Marano F, Berta L, Bosco O, Fraccalvieri M, Fortunati N, et al
. Extracorporeal shock waves modulate myofibroblast differentiation of adipose-derived stem cells. Wound Repair Regen 2016;24:275-86.
Cacchio A, Giordano L, Colafarina O, Rompe JD, Tavernese E, Ioppolo F, et al
. Extracorporeal shock-wave therapy compared with surgery for hypertrophic long-bone nonunions. J Bone Joint Surg Am 2009;91:2589-97.
Haffner N, Antonic V, Smolen D, Slezak P, Schaden W, Mittermayr R, et al
. Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy. Injury 2016;47:1506-13.
Wang FS, Yang KD, Kuo YR, Wang CJ, Sheen-Chen SM, Huang HC, et al
. Temporal and spatial expression of bone morphogenetic proteins in extracorporeal shock wave-promoted healing of segmental defect. Bone 2003;32:387-96.
Chen YJ, Wurtz T, Wang CJ, Kuo YR, Yang KD, Huang HC, et al
. Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats. J Orthop Res 2004;22:526-34.
Wang CJ, Yang KD, Ko JY, Huang CC, Huang HY, Wang FS. The effects of shockwave on bone healing and systemic concentrations of nitric oxide (NO), TGF-beta1, VEGF and BMP-2 in long bone non-unions. Nitric Oxide 2009;20:298-303.
Hofmann A, Ritz U, Hessmann MH, Alini M, Rommens PM, Rompe JD. Extracorporeal shock wave-mediated changes in proliferation, differentiation, and gene expression of human osteoblasts. J Trauma 2008;65:1402-10.
Bahar E, Kim H, Yoon H. ER stress-mediated signaling: Action potential and Ca(2+) as key players. Int J Mol Sci 2016;17:1558.
Wang B, Ning H, Reed-Maldonado AB, Zhou J, Ruan Y, Zhou T, et al
. Low-intensity extracorporeal shock wave therapy enhances brain-derived neurotrophic factor expression through PERK/ATF4 signaling pathway. Int J Mol Sci 2017;18:433.
Lie DC, Colamarino SA, Song HJ, Désiré L, Mira H, Consiglio A, et al
. Wnt signalling regulates adult hippocampal neurogenesis. Nature 2005;437:1370-5.
Peng D, Yuan H, Liu T, Wang T, Reed-Maldonado AB, Kang N, et al
. Smooth muscle differentiation of penile stem/progenitor cells induced by microenergy acoustic pulses in vitro
. J Sex Med 2019;16:1874-84.
Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer. Lancet Oncol 2005;6:322-7.
Weihs AM, Fuchs C, Teuschl AH, Hartinger J, Slezak P, Mittermayr R, 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 2014;289:27090-104.