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Kananivand M, Nouri F, Yousefi MH, Pajouhi A, Ghorbani H, Afkhami H, Razavi ZS. Mesenchymal stem cells and their exosomes: a novel approach to skin regeneration via signaling pathways activation. J Mol Histol 2025; 56:132. [PMID: 40208456 DOI: 10.1007/s10735-025-10394-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 03/06/2025] [Indexed: 04/11/2025]
Abstract
Accelerating wound healing is a crucial objective in surgical and regenerative medicine. The wound healing process involves three key stages: inflammation, cell proliferation, and tissue repair. Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in promoting tissue regeneration, particularly by enhancing epidermal cell migration and proliferation. However, the precise molecular mechanisms underlying MSC-mediated wound healing remain unclear. This review highlights the pivotal role of MSCs and their exosomes in wound repair, with a specific focus on critical signaling pathways, including PI3K/Akt, WNT/β-catenin, Notch, and MAPK. These pathways regulate essential cellular processes such as proliferation, differentiation, and angiogenesis. Moreover, in vitro and in vivo studies reveal that MSCs accelerate wound closure, enhance collagen deposition, and modulate immune responses, contributing to improved tissue regeneration. Understanding these mechanisms provides valuable insights into MSC-based therapeutic strategies for enhancing wound healing.
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Affiliation(s)
- Maryam Kananivand
- Medical Department, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Fatemeh Nouri
- Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University (SRBIAU), Tehran, Iran
| | - Mohammad Hasan Yousefi
- Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
- Student Research Committee, Qom University of Medical Sciences, Qom, Iran
| | - Ali Pajouhi
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Hakimeah Ghorbani
- Department of Sciences, Faculty of Biological Sciences, Tabriz University of Sciences, Tabriz, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
- Student Research Committee, Qom University of Medical Sciences, Qom, Iran.
| | - Zahra Sadat Razavi
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Hari Priya VM, Ganapathy A A, Veeran MG, Raphael M S, Kumaran A. Nanotechnology-based drug delivery platforms for erectile dysfunction: addressing efficacy, safety, and bioavailability concerns. Pharm Dev Technol 2024; 29:996-1015. [PMID: 39392251 DOI: 10.1080/10837450.2024.2414379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/04/2024] [Accepted: 10/06/2024] [Indexed: 10/12/2024]
Abstract
Erectile dysfunction (ED), is a common and multidimensional sexual disorder, which comprises changes among any of the processes of the erectile response such as organic, relational, and psychological. However, both endocrine and nonendocrine causes of ED produce substantial health implications including depression and anxiety due to poor sexual performance, eventually affecting man's life eminence. Marginally invasive interventions following ED consist of lifestyle modifications, oral drugs, injections, vacuum erection devices, etc. Nevertheless, these conventional treatment regimens follow certain drawbacks such as efficacy and safety issues, and navigate to the development of novel therapeutic approaches such as nanomedicine for ED management. Nanotechnology-centred drug delivery platforms are being explored to minimize these limitations with better in vitro and in vivo effectiveness. Moreover, nanomedicine and nanocarrier-linked approaches are rapidly developing science in the nanoscale range, which contributes to site-specific delivery in a controlled manner and has generated considerable interest prominent to their potential to enhance bioavailability, decrease side effects, and avoidance of first-pass metabolism. This review provides an overview of recent discoveries regarding various nanocarriers and nano-delivery methods, along with current trends in the clinical aspects of ED. Additionally, strategies for clinical translation have been incorporated.
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Affiliation(s)
- Vijayakumari Mahadevan Hari Priya
- Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Anand Ganapathy A
- Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Midhu George Veeran
- Corporate Research and Development Centre (CRDC), HLL Lifecare Ltd, Akkulam, Thiruvananthapuram, India
| | - Shyni Raphael M
- Department of Chemistry, Government College for Women, Thiruvananthapuram, India
| | - Alaganandam Kumaran
- Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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Kou D, Chen Q, Wang Y, Xu G, Lei M, Tang X, Ni H, Zhang F. The application of extracorporeal shock wave therapy on stem cells therapy to treat various diseases. Stem Cell Res Ther 2024; 15:271. [PMID: 39183302 PMCID: PMC11346138 DOI: 10.1186/s13287-024-03888-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/16/2024] [Indexed: 08/27/2024] Open
Abstract
In the last ten years, stem cell (SC) therapy has been extensively used to treat a range of conditions such as degenerative illnesses, ischemia-related organ dysfunction, diabetes, and neurological disorders. However, the clinical application of these therapies is limited due to the poor survival and differentiation potential of stem cells (SCs). Extracorporeal shock wave therapy (ESWT), as a non-invasive therapy, has shown great application potential in enhancing the proliferation, differentiation, migration, and recruitment of stem cells, offering new possibilities for utilizing ESWT in conjunction with stem cells for the treatment of different systemic conditions. The review provides a detailed overview of the advances in using ESWT with SCs to treat musculoskeletal, cardiovascular, genitourinary, and nervous system conditions, suggesting that ESWT is a promising strategy for enhancing the efficacy of SC therapy for various diseases.
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Affiliation(s)
- Dongyan Kou
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Qingyu Chen
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Yujing Wang
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Guangyu Xu
- Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, PR China
| | - Mingcheng Lei
- Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, PR China
| | - Xiaobin Tang
- Department of Rehabilitation Medicine, CNPC Central Hospital, Langfang, 065000, PR China
| | - Hongbin Ni
- Department of Neurosurgery, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
| | - Feng Zhang
- Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, PR China.
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Kennady EH, Bryk DJ, Ali MM, Ratcliffe SJ, Mallawaarachchi IV, Ostad BJ, Beano HM, Ballantyne CC, Krzastek SC, Clements MB, Gray ML, Rapp DE, Ortiz NM, Smith RP. Low-intensity shockwave therapy improves baseline erectile function: a randomized sham-controlled crossover trial. Sex Med 2023; 11:qfad053. [PMID: 37965376 PMCID: PMC10642534 DOI: 10.1093/sexmed/qfad053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 08/19/2023] [Accepted: 09/27/2023] [Indexed: 11/16/2023] Open
Abstract
Background Low-intensity shockwave therapy for erectile dysfunction is emerging as a promising treatment option. Aim This randomized sham-controlled crossover trial assessed the efficacy of low-intensity shockwave therapy in the treatment of erectile dysfunction. Methods Thirty-three participants with organic erectile dysfunction were enrolled and randomized to shockwave therapy (n = 17) or sham (n = 16). The sham group was allowed to cross over to receive shockwave therapy after 1 month. Outcomes Primary outcomes were the changes in Sexual Health Inventory for Men (SHIM) score and Erection Hardness Score at 1 month following shockwave therapy vs sham, and secondary outcomes were erectile function measurements at 1, 3, and 6 months following shockwave therapy. Results At 1 month, mean SHIM scores were significantly increased in the shockwave therapy arm as compared with the sham arm (+3.0 vs -0.7, P = .024). Participants at 6 months posttreatment (n = 33) showed a mean increase of 5.5 points vs baseline (P < .001), with 20 (54.6%) having an increase ≥5. Of the 25 men with an initial Erection Hardness Score <3, 68% improved to a score ≥3 at 6 months. When compared with baseline, the entire cohort demonstrated significant increases in erectile function outcomes at 1, 3, and 6 months after treatment. Clinical Implications In this randomized sham-controlled crossover trial, we showed that 54.6% of participants with organic erectile dysfunction met the minimal clinically important difference in SHIM scores after treatment with low-intensity shockwave therapy. Strengths and Limitations Strengths of this study include a sham-controlled group that crossed over to treatment. Limitations include a modest sample size at a single institution. Conclusions Low-intensity shockwave therapy improves erectile function in men with erectile dysfunction as compared with sham treatment, which persists even 6 months after treatment. Clinical Trial Registration ClinicalTrials.gov NCT04434352.
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Affiliation(s)
- Emmett H Kennady
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Darren J Bryk
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Marwan M Ali
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Sarah J Ratcliffe
- Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA 22903, United States
| | - Indika V Mallawaarachchi
- Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA 22903, United States
| | - Bahrom J Ostad
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Hamza M Beano
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | | | - Sarah C Krzastek
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Matthew B Clements
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Mikel L Gray
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - David E Rapp
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Nicolas M Ortiz
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
| | - Ryan P Smith
- Department of Urology, University of Virginia, Charlottesville, VA 22903, United States
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Chung E, Bailey W, Wang J. A Prospective, Randomized, Double-Blinded, Clinical Trial Using a Second-Generation Duolith SD1 Low-Intensity Shockwave Machine in Males with Vascular Erectile Dysfunction. World J Mens Health 2023; 41:94-100. [PMID: 35021310 PMCID: PMC9826910 DOI: 10.5534/wjmh.210123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 10/17/2021] [Accepted: 10/17/2021] [Indexed: 01/21/2023] Open
Abstract
PURPOSE To evaluate the clinical efficacy and patient satisfaction rates of low-intensity extracorporeal shockwave therapy LIESWT) in men with vasculogenic erectile dysfunction (ED) using Duolith SD1 machine. MATERIALS AND METHODS This prospective, randomized, double-blinded clinical trial included 60 men who were randomly assigned to LIESWT (n=30, active group) or placebo (n=30) over 6 weeks. Patient demographics, change in International Index of Erectile Function (IIEF)-5, Erection Hardness Score (EHS) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores, and an overall satisfaction score (on a 5-point scale), were recorded. All patients were reviewed at 1, 3, and 6 months after completion of therapy. RESULTS There were 21 (70%) patients in the LIESWT group and 3 (10%) patients in the placebo group who had a 5-point or greater increase in IIEF-5 score (p=0.018). At 6-month study period, the mean IIEF-5 score was 18.8 (standard deviation [SD], 3.8) in the LIESWT group versus 14.8 (SD, 3.6) in the placebo group, difference in means between groups was 4.0 (95% confidence interval, 2.1-5.9; p<0.001). The EHS scores were higher in the LIESWT group with a mean of greater than 1.2 across the 1, 3, and 6 months compared to the placebo group (p<0.05). All patients completed the treatment study and there was no adverse event reported in terms of penile pain, bruising or deformity. There was a positive correlation between men who reported improvement in EF and treatment satisfaction level with LiESWT (p=0.008). CONCLUSIONS LIESWT improves erectile function in the short-term especially in men with mild to moderate ED, and those without a cardiometabolic disease.
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Affiliation(s)
- Eric Chung
- Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia.,AndroUrology Centre, St Andrew's War Memorial Hospital, Brisbane, QLD, Australia
| | - William Bailey
- Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia
| | - Juan Wang
- AndroUrology Centre, St Andrew's War Memorial Hospital, Brisbane, QLD, Australia
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Xing J, Yu G, Xiang Y, Xu H, Liu Z, Bai Z. Effect of low energy shock wave on testicular microenvironment homeostasis in rats. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 241:113710. [PMID: 35679733 DOI: 10.1016/j.ecoenv.2022.113710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 05/23/2022] [Accepted: 05/24/2022] [Indexed: 06/15/2023]
Abstract
OBJECTIVE To further investigate whether two sets of low-energy extracorporeal shock waves (LESWs) impulse parameters, i.e., 0.02 mJ/mm2 for 500 impulses and 0.04 mJ/mm2 for 500 impulses, which have been shown to directly affect the testes, can promote testicular spermatogenesis or positively regulate homeostasis of the testicular microenvironment. METHODS (1) Twenty-four experimental rats were randomly divided into a 0.02 mJ/mm2 500 impulses group (L1 group), a 0.04 mJ/mm2 500 impulses group (M1 group), a sham intervention group (S group) and a blank control group (N group). The experiment period was 8 weeks. (2) Apoptosis of the spermatogenic cells in the left testicle was detected by the TUNEL method, VEGF and eNOs protein expression was detected by immunohistochemistry, and histomorphological changes were observed in PAS-stained sections. Moreover, the morphologies of the spermatogenic tubules and testicular stroma were quantitatively analyzed by stereological analysis. The right testicle was used for Western blot detection of the protein expression levels of Bax, Cytochrome C, Caspase-3, Bcl-2, VEGF and eNOs. RESULTS Compared with the other three groups, the rate of M1 testicular germ cell apoptosis induced by shock treatment was higher, the expression levels of proapoptotic proteins increased significantly while that of the antiapoptotic protein was lower, and the suppression of cell proliferation correlated with the protein expression levels. Additionally, with respect to the absolute volume of the seminiferous tubules, the absolute interstitial testicular volume notably increased, producing a series of biological effects working against testicular sperm production and function. However, there was no significant difference between the L1 group and the N and S groups. CONCLUSIONS LESWs treatment with impulse parameters of 0.02 mJ/mm2 for 500 impulses showed a better protective effect on testicular spermatic function in rats and has a positive regulatory biological effect.
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Affiliation(s)
- Jiansheng Xing
- Department of Urology and Pathology, Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China.
| | - Gang Yu
- Department of Urology, Renmin Hospital of Wuhan University Hubei General Hospital, Wuhan 430060, Hubei Province, China
| | - Yang Xiang
- Department of Urology and Pathology, Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Haixia Xu
- Department of Pathology, Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Zhenxiang Liu
- Department of Urology and Pathology, Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Zhiming Bai
- Department of Urology and Pathology, Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China.
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Liraglutide may affect visceral fat accumulation in diabetic rats via changes in FTO, AMPK, and AKT expression. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00974-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Abstract
Purpose
The aim of this study is to explore the effects of liraglutide (LRG) on the expression of FTO, AMPK, and AKT in the visceral adipose tissues of obese and diabetic rats and the underlying mechanisms thereof.
Methods
Thirty SPF-grade, male SD rats were randomly divided into the healthy control, diabetic model (DM), and DM + LRG groups. The DM and DM + LRG groups were administered normal saline and LRG (0.6 mg/kg/d), respectively. After 12 weeks, the body weight of the rats was measured, and their visceral adipose tissues were collected and weighed; the levels of serum biochemical indicators and FTO, AMPK, and AKT in these tissues were then measured using qRT-PCR and western blotting.
Results
Compared to the control group, the body weight and visceral fat accumulation and blood glucose, TG, TC, and LDL-C levels increased significantly, while the HDL-C levels decreased significantly, in the DM group (p < 0.05). After LRG treatment, the HDL-C levels increased significantly, but the levels of the other indicators decreased significantly (p < 0.05). Compared to the control group, the visceral adipose tissue levels of FTO and AKT increased significantly, while the AMPK levels decreased significantly in the DM group (p < 0.05). After LRG treatment, the FTO and AKT levels decreased significantly, and the AMPK levels increased significantly (p < 0.05).
Conclusion
LRG may activate and inhibit the AMPK and AKT pathways, respectively, and decrease FTO expression, thereby alleviating abdominal obesity in type 2 diabetes.
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Mittermayr R, Haffner N, Feichtinger X, Schaden W. The role of shockwaves in the enhancement of bone repair - from basic principles to clinical application. Injury 2021; 52 Suppl 2:S84-S90. [PMID: 33714550 DOI: 10.1016/j.injury.2021.02.081] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 02/19/2021] [Accepted: 02/22/2021] [Indexed: 02/02/2023]
Abstract
Extracorporeal shockwave therapy is a treatment modality, originally introduced into the clinic as lithotripsie, which has also been successfully used in the last two decades in the non-invasive treatment of delayed or non-healing fractures. Initially, the mechanism of action was attributed to microfracture-induced repair, but intensive basic research has now shown that the shockwave generates its effect in tissue via mechanotransduction. Numerous signal transduction pathways have already been demonstrated, which in their entirety trigger an endogenous regeneration process via cell proliferation, migration and differentiation. Clinically, these shockwave-conveyed biological signals support healing of acute, delayed and non-union fractures. The attainable outcome is comparable to surgery but avoiding an open approach with associated potential complications. These advantageous properties with a clearly positive cost-benefit ratio make shockwave therapy a first line treatment in delayed and non-union fractures.
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Affiliation(s)
- Rainer Mittermayr
- Ludwig Boltzmann Institute for experimental and clinical traumatology, Vienna, Austria; AUVA Trauma Center Meidling, Vienna, Austria; AUVA trauma research center, Vienna, Austria; Austrian Cluster for Tissue Engineering, Vienna, Austria.
| | - Nicolas Haffner
- Ludwig Boltzmann Institute for experimental and clinical traumatology, Vienna, Austria; Clinic Floridsdorf, Orthopedic and Traumatology Department, Vienna, Austria
| | | | - Wolfgang Schaden
- Ludwig Boltzmann Institute for experimental and clinical traumatology, Vienna, Austria; AUVA trauma research center, Vienna, Austria; Austrian Cluster for Tissue Engineering, Vienna, Austria; AUVA Medical Board, Vienna, Austria
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Integrin β1 in Adipose-Derived Stem Cells Accelerates Wound Healing via Activating PI3K/AKT Pathway. Tissue Eng Regen Med 2020; 17:183-192. [PMID: 32200515 DOI: 10.1007/s13770-019-00229-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 10/27/2019] [Accepted: 11/01/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND This study aims to investigate the effect of integrin β1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism. METHODS Integrin β1 was overexpressed in ADSCs. Thereafter, flow cytometry and transwell chambers technology were used to measure the endothelial-like differentiation (CD31 as a biomarker of endothelial cell) and cell migration, respectively. Western blot was used to detect the activation of PI3K/AKT, NF-κB and ERK signaling pathways. The effects of integrin β1 overexpression on healing time, healing rate and fibroblast number were further evaluated in the rat models of chronic refractory wound. RESULTS The overexpression of integrin β1 increased CD31+ endothelial-like cells (about 3.6-fold), promoted cell migration (about 1.9-fold) and enhanced the activation of PI3K (p-PI3K; about 2.1-fold) and AKT (p-AKT; about 2.2-fold). These effects were all weakened when PI3K/AKT pathway was inhibited by LY294002 treatment. In addition, the experiments in rat wound models showed that integrin β1 overexpression obviously shortened healing time (approximately 0.41-fold), increased healing rate (about 2.7-fold, 2.8-fold and 1.6-fold at day 7, 14 and 21) and increased the number of fibroblasts (approximately 3.1-fold at day 21). All of the above differences were statistically significant (p < 0.05). CONCLUSION Integrin β1 can promote the migration and endothelial-like differentiation of ADSCs by activating PI3K/AKT pathway and then enhance the function of ADSCs in promoting wound healing.
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Haider KH, Aramini B. Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy. Stem Cell Res Ther 2020; 11:23. [PMID: 31918755 PMCID: PMC6953131 DOI: 10.1186/s13287-019-1548-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/18/2019] [Accepted: 12/29/2019] [Indexed: 02/06/2023] Open
Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) have successfully progressed to phase III clinical trials successive to an intensive in vitro and pre-clinical assessment in experimental animal models of ischemic myocardial injury. With scanty evidence regarding their cardiogenic differentiation in the recipient patients' hearts post-engraftment, paracrine secretion of bioactive molecules is being accepted as the most probable underlying mechanism to interpret the beneficial effects of cell therapy. Secretion of small non-coding microRNA (miR) constitutes an integral part of the paracrine activity of stem cells, and there is emerging interest in miRs' delivery to the heart as part of cell-free therapy to exploit their integral role in various cellular processes. MSCs also release membrane vesicles of diverse sizes loaded with a wide array of miRs as part of their paracrine secretions primarily for intercellular communication and to shuttle genetic material. Exosomes can also be loaded with miRs of interest for delivery to the organs of interest including the heart, and hence, exosome-based cell-free therapy is being assessed for cell-free therapy as an alternative to cell-based therapy. This review of literature provides an update on cell-free therapy with primary focus on exosomes derived from BM-derived MSCs for myocardial repair.
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Affiliation(s)
- Khawaja Husnain Haider
- Sulaiman Alrajhi University, Al-Qaseem, Kingdom of Saudi Arabia
- Department of Basic Sciences, Sulaiman Alrajhi University, PO Box 777, Al Bukairiyah, 51941 Kingdom of Saudi Arabia
| | - Beatrice Aramini
- Division of Thoracic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
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Chung E. A Review of Current and Emerging Therapeutic Options for Erectile Dysfunction. Med Sci (Basel) 2019; 7:medsci7090091. [PMID: 31470689 PMCID: PMC6780857 DOI: 10.3390/medsci7090091] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 08/20/2019] [Accepted: 08/23/2019] [Indexed: 12/23/2022] Open
Abstract
Contemporary treatment algorithms for erectile dysfunction (ED) involve the use of medical therapies such as phosphodiesterase type 5 (PDE5) inhibitors and intracavernosal injection therapy of vasoactive agents, as well as vacuum erection devices and penile prosthesis implants in medically refractory cases. However, the current therapeutic options only address the symptoms of ED and not the underlying pathogenesis that results in ED. Newer and novel ED therapies aspire to reverse ED conditions by preventing cavernosal fibrosis, promoting endothelial revascularization and modulating various neuro-hormonal pathways. Regenerative therapeutic strategies such as low-intensity shock wave, gene and cellular-based therapies, and penile transplants are designed to improve penile hemodynamics and revitalize the cavernosal smooth muscle to mitigate and/or reverse underlying ED. This state-of-art article evaluates current and emerging therapeutic options for ED.
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Affiliation(s)
- Eric Chung
- AndroUrology Centre, Brisbane, QLD 4000, Australia.
- University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
- Macquarie University Hospital, Sydney, NSW 2109, Australia.
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Facchin F, Canaider S, Tassinari R, Zannini C, Bianconi E, Taglioli V, Olivi E, Cavallini C, Tausel M, Ventura C. Physical energies to the rescue of damaged tissues. World J Stem Cells 2019; 11:297-321. [PMID: 31293714 PMCID: PMC6600852 DOI: 10.4252/wjsc.v11.i6.297] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/24/2019] [Accepted: 05/29/2019] [Indexed: 02/06/2023] Open
Abstract
Rhythmic oscillatory patterns sustain cellular dynamics, driving the concerted action of regulatory molecules, microtubules, and molecular motors. We describe cellular microtubules as oscillators capable of synchronization and swarming, generating mechanical and electric patterns that impact biomolecular recognition. We consider the biological relevance of seeing the inside of cells populated by a network of molecules that behave as bioelectronic circuits and chromophores. We discuss the novel perspectives disclosed by mechanobiology, bioelectromagnetism, and photobiomodulation, both in term of fundamental basic science and in light of the biomedical implication of using physical energies to govern (stem) cell fate. We focus on the feasibility of exploiting atomic force microscopy and hyperspectral imaging to detect signatures of nanomotions and electromagnetic radiation (light), respectively, generated by the stem cells across the specification of their multilineage repertoire. The chance is reported of using these signatures and the diffusive features of physical waves to direct specifically the differentiation program of stem cells in situ, where they already are resident in all the tissues of the human body. We discuss how this strategy may pave the way to a regenerative and precision medicine without the needs for (stem) cell or tissue transplantation. We describe a novel paradigm based upon boosting our inherent ability for self-healing.
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Affiliation(s)
- Federica Facchin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Silvia Canaider
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Riccardo Tassinari
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Chiara Zannini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Eva Bianconi
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Valentina Taglioli
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Elena Olivi
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Claudia Cavallini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | | | - Carlo Ventura
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy.
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Li G, Yu H, Liu N, Zhang P, Tang Y, Hu Y, Zhang Y, Pan C, Deng H, Wang J, Li Q, Tang Z. Overexpression of CX3CR1 in Adipose-Derived Stem Cells Promotes Cell Migration and Functional Recovery After Experimental Intracerebral Hemorrhage. Front Neurosci 2019; 13:462. [PMID: 31133793 PMCID: PMC6517499 DOI: 10.3389/fnins.2019.00462] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 04/24/2019] [Indexed: 12/13/2022] Open
Abstract
Stem cell therapy has emerged as a new promising therapeutic strategy for intracerebral hemorrhage (ICH). However, the efficiency of stem cell therapy is partially limited by low retention and engraftment of the delivered cells. Therefore, it’s necessary to improve the migration ability of stem cells to the injured area in order to save the costs and duration of cell preparation. This study aimed to investigate whether overexpression of CX3CR1, the specific receptor of chemokine fractalkine (FKN), in adipose-derived stem cells (ADSCs) can stimulate the cell migration to the injured area in the brain, improve functional recovery and protect against cell death following experimental ICH. ADSCs were isolated from subcutaneous adipose tissues of rats. ICH was induced by means of an injection of collagenase type VII. ELISA showed that the expression levels of fractalkine/FKN were increased at early time points, with a peak at day 3 after ICH. And it was found that different passages of ADSCs could express the chemokine receptor CX3CR1. Besides, the chemotactic movements of ADSCs toward fractalkine have been verified by transwell migration assay. ADSCs overexpressing CX3CR1 were established through lentivirus transfection. We found that after overexpression of CX3CR1 receptor, the migration ability of ADSCs was increased both in vitro and in vivo. In addition, reduced cell death and improved sensory and motor functions were seen in the mice ICH model. Thus, ADSCs overexpression CX3CR1 might be taken as a promising therapeutic strategy for the treatment of ICH.
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Affiliation(s)
- Gaigai Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haihan Yu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Na Liu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ping Zhang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yingxin Tang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Hu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ye Zhang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chao Pan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Deng
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiahui Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Li
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhouping Tang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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14
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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; 13:986-996. [PMID: 30811857 DOI: 10.1002/term.2844] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 01/18/2019] [Accepted: 02/21/2019] [Indexed: 12/19/2022]
Abstract
Adipose tissue-derived stem cells (ADSCs) have shown effectiveness in treating diabetic bladder dysfunction (DBD). In the present study, ADSCs pretreated by defocused low-energy shock wave (DLSW) were first used to achieve better therapeutic effect. ADSCs were treated by DLSW prior to each passage. Secretions of vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) were tested. Proliferation ability was examined by staining 5-ethynyl-2-deoxyuridine (EdU) and assessing expressions of proliferating cell nuclear antigen (PCNA) and Ki67. DBD rat model was created and subgrouped via therapeutic options of phosphate-buffered saline, ADSCs, pretreated ADSCs, and ADSCs lysate. Afterward, voiding functions were evaluated, and tissues were examined by histology. Neonatal rats received intraperitoneal injection of EdU. All rats were subgrouped and treated as narrated above. Bladder tissues were stained with EdU, Stro-1, and CD34. Results showed that shocked ADSCs were activated by secreting more VEGF and NGF, by higher EdU-retaining cells ratios, and by higher expressions of PCNA and Ki67 compared with unshocked ADSCs. Shocked ADSCs had the most effective efficacy in treating DBD by secreting the most VEGF and NGF to accelerate regenerations of revascularization and innervation. Migrations of EdU+ Stro-1+ CD34- endogenous stem cells to bladders were enhanced by injecting ADSCs. In conclusion, ADSCs pretreated by DLSW had potent therapeutic effect in treating DBD by secreting VEGF and NGF. Recruitment of endogenous stem cells was considered as an important mechanism in this regenerative process.
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Affiliation(s)
- Haiyang Zhang
- School of Basic Medical Sciences, Shandong University, Jinan, China.,Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.,Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA
| | - Yong Zhao
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Muwen Wang
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Wei Song
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Peng Sun
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Xunbo Jin
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
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15
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Yu G, Guan Y, Liu L, Xing J, Li J, Cheng Q, Liu Z, Bai Z. The protective effect of low-energy shock wave on testicular ischemia-reperfusion injury is mediated by the PI3K/AKT/NRF2 pathway. Life Sci 2018; 213:142-148. [PMID: 30321543 DOI: 10.1016/j.lfs.2018.10.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 10/07/2018] [Accepted: 10/11/2018] [Indexed: 12/14/2022]
Abstract
AIMS Testicular ischemia-reperfusion (IR) injury is the primary pathophysiological consequence of testicular torsion. Low-energy shock wave (LESW) is an effective treatment for certain diseases. The present study investigated whether LESW could improve on testicular IR injury in rats and examined the involved mechanism. MAIN METHODS Testicular reperfusion was induced in rats after 1-h ischemia. The first LESW treatment was performed 30 min prior to testicular reperfusion, and then every other day for another 3 applications. LY294002 was applied to investigate the involved mechanism. Testicular morphological changes and malonaldehyde (MDA) level were respectively assessed by hematoxylin-eosin staining. Western blot and thiobarbituric acid method. Western blot, real-time quantitative PCR and immunohistochemistry were performed to assess the apoptosis, the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) pathway the nuclear factor erythroid 2-related factor 2 (NRF2) and vascular endothelial growth factor A (VEGF-A) level in the testis of rats. KEY FINDINGS LESW improved testicular IR injury in rats. Moreover, LESW upregulated the phosphorylation levels of AKT and glycogen synthase kinase 3β (GSK-3β). Also, it upregulated the levels of nuclear NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) in these rats. Nevertheless, LY294002 blocked these protective effects. LESW also upregulated VEGF-A level in rats with testicular IR injury. SIGNIFICANCE This study demonstrated that LESW could ameliorate testicular IR injury in rats, which might be attributed to the activation of PI3K/AKT/NRF2 pathway. These findings suggested the potential of LESW in the treatment of testicular torsion.
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Affiliation(s)
- Gang Yu
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China; Haikou Center for Medical Synchrotron Radiation Research, Haikou People's Hospital, Haikou 570208, Hainan Province, China
| | - Yupeng Guan
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China; Haikou Center for Medical Synchrotron Radiation Research, Haikou People's Hospital, Haikou 570208, Hainan Province, China
| | - Lin Liu
- Emergency and Critical Care Center, Shiyan People's Hospital, Shiyan 442000, Hubei Province, China
| | - Jiansheng Xing
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Jindong Li
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Qing Cheng
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Zhenxiang Liu
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China
| | - Zhiming Bai
- Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China; Haikou Center for Medical Synchrotron Radiation Research, Haikou People's Hospital, Haikou 570208, Hainan Province, China.
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16
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Facchin F, Bianconi E, Canaider S, Basoli V, Biava PM, Ventura C. Tissue Regeneration without Stem Cell Transplantation: Self-Healing Potential from Ancestral Chemistry and Physical Energies. Stem Cells Int 2018; 2018:7412035. [PMID: 30057626 PMCID: PMC6051063 DOI: 10.1155/2018/7412035] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 06/20/2018] [Indexed: 12/17/2022] Open
Abstract
The human body constantly regenerates after damage due to the self-renewing and differentiating properties of its resident stem cells. To recover the damaged tissues and regenerate functional organs, scientific research in the field of regenerative medicine is firmly trying to understand the molecular mechanisms through which the regenerative potential of stem cells may be unfolded into a clinical application. The finding that some organisms are capable of regenerative processes and the study of conserved evolutionary patterns in tissue regeneration may lead to the identification of natural molecules of ancestral species capable to extend their regenerative potential to human tissues. Such a possibility has also been strongly suggested as a result of the use of physical energies, such as electromagnetic fields and mechanical vibrations in human adult stem cells. Results from scientific studies on stem cell modulation confirm the possibility to afford a chemical manipulation of stem cell fate in vitro and pave the way to the use of natural molecules, as well as electromagnetic fields and mechanical vibrations to target human stem cells in their niche inside the body, enhancing human natural ability for self-healing.
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Affiliation(s)
- Federica Facchin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
- National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) - Eldor Lab, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy
| | - Eva Bianconi
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
- National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) - Eldor Lab, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy
| | - Silvia Canaider
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
- National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) - Eldor Lab, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy
| | - Valentina Basoli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
| | - Pier Mario Biava
- Scientific Institute of Research and Care Multimedica, Via Milanese 300, 20099 Sesto San Giovanni, Italy
| | - Carlo Ventura
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
- National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) - Eldor Lab, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy
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17
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Chung E, Wang J. A state-of-art review of low intensity extracorporeal shock wave therapy and lithotripter machines for the treatment of erectile dysfunction. Expert Rev Med Devices 2017; 14:929-934. [PMID: 29119841 DOI: 10.1080/17434440.2017.1403897] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Current treatment for erectile dysfunction (ED) mostly attempts to improve erectile function with limited impact on altering the underlying pathophysiology of ED. Recent animal experiments have supported the notion that low intensity extracorporeal shockwave therapy (LIESWT) significantly improves penile hemodynamics and might induce structural changes that regenerate penile tissue. Areas covered: This review article provides an overview of the basic mechanics and clinical studies pertaining to LIESWT and its use in the field of ED. We identify several key aspects of LIESWT and compare contemporary LIESWT machines and their clinical outcomes. Expert commentary: There is emerging and strong literature to support the use of LIESWT in men with ED, with many clinical studies reported encouraging results in the use of LIESWT with improved erectile function, good safety records, and short-term durability. However, there is a need to define which subgroup of ED population is best suited and the LIESWT treatment protocol including LIESWT template, modality of shock waves energy, emission frequency, and total energy delivery. More stringent randomised controlled trials are warranted before there is widespread acceptance of this LIESWT technology as the standard of care in ED.
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Affiliation(s)
- Eric Chung
- a Department of Urology, Princess Alexandra Hospital , University of Queensland , Brisbane , Australia.,b AndroUrology Centre , St Andrew's War Memorial Hospital , Brisbane , Australia
| | - Juan Wang
- b AndroUrology Centre , St Andrew's War Memorial Hospital , Brisbane , Australia
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18
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Endogenous Stem Cells Were Recruited by Defocused Low-Energy Shock Wave in Treating Diabetic Bladder Dysfunction. Stem Cell Rev Rep 2017; 13:287-298. [PMID: 27921202 DOI: 10.1007/s12015-016-9705-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Defocused low-energy shock wave (DLSW) has been shown effects on activating mesenchymal stromal cells (MSCs) in vitro. In this study, recruitment of endogenous stem cells was firstly examined as an important pathway during the healing process of diabetic bladder dysfunction (DBD) treated by DLSW in vivo. Neonatal rats received intraperitoneal injection of 5-ethynyl-2-deoxyuridine (EdU) and then DBD rat model was created by injecting streptozotocin. Four weeks later, DLSW treatment was performed. Afterward, their tissues were examined by histology. Meanwhile, adipose tissue-derived stem cells (ADSCs) were treated by DLSW in vitro. Results showed DLSW ameliorated voiding function of diabetic rats by recruiting EdU+Stro-1+CD34- endogenous stem cells to release abundant nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Some EdU+ cells overlapped with staining of smooth muscle actin. After DLSW treatment, ADSCs showed higher migration ability, higher expression level of stromal cell-derived factor-1 and secreted more NGF and VEGF. In conclusion, DLSW could ameliorate DBD by recruiting endogenous stem cells. Beneficial effects were mediated by secreting NGF and VEGF, resulting into improved innervation and vascularization in bladder.
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19
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Wang B, Zhou J, Banie L, Reed-Maldonado AB, Ning H, Lu Z, Ruan Y, Zhou T, Wang HS, Oh BS, Wang G, Qi SL, Lin G, Lue TF. Low-intensity extracorporeal shock wave therapy promotes myogenesis through PERK/ATF4 pathway. Neurourol Urodyn 2017; 37:699-707. [PMID: 28763567 DOI: 10.1002/nau.23380] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 07/10/2017] [Indexed: 12/27/2022]
Abstract
AIM Stress urinary incontinence (SUI) is a significant health problem for women. Treatments employing muscle derived stem cells (MDSCs) may be a promising approach to this prevalent, bothersome condition, but these treatments are invasive and require collection of cells from one site for injection into another. It is also unknown whether or not these cells establish themselves and function as muscle cells in the target tissues. Alternatively, low-intensity extracorporeal shock wave therapy (Li-ESWT) is non-invasive and has shown positive outcomes in the treatment of multiple musculoskeletal disorders, but the biological effects responsible for clinical success are not yet well understood. The aim of this study is to explore the possibility of employing Li-ESWT for activation of MDSCs in situ and to further elucidate the underlying biological effects and mechanisms of action in urethral muscle. METHODS Urethral muscle derived stem cells (uMDSCs) were harvest from Zucker Lean (ZUC-LEAN) (ZUC-Leprfa 186) rats and characterized with flow cytometry. Li-ESWT (0.02 mJ/mm2 , 3 Hz, 200 pulses) and GSK2656157, an inhibitor of PERK pathway, were applied to L6 rat myoblast cells. To assess for myotube formation, we used immunofluorescence staining and western blot analysis in uMDSCs and L6 cells. RESULTS The results indicate that uMDSCs could form myotubes. Myotube formation was significantly increased by the Li-ESWT as was the expression of muscle heavy chain (MHC) and myogenic factor 5 (Myf5) in L6 cells in vitro. Li-ESWT activated protein kinase RNA-like ER kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α) and by increasing activating transcription factor 4 (ATF4). In addition, GSK2656157, an inhibitor of PERK, effectively inhibited the myotube formation in L6 rat myoblast cells. Furthermore, GSK2656157 also attenuated myotube formation induced by Li-ESWT. CONCLUSION In conclusion, this experiment reveals that rat uMDSCs can be isolated successfully and can form myotubes in vitro. PERK/ATF4 pathway was involved in myotube formation, and L6 rat myoblast cells were activated by Li-ESWT to form myotubes. These findings suggest that PERK/ATF4 pathway is activated by Li-ESWT. This study elucidates one of the biochemical pathways responsible for the clinical improvements seen after Li-ESWT. It is possible that this information will help to establish Li-ESWT as an acceptable treatment modality and may help to further refine the use of Li-ESWT in the clinical practice of medicine.
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Affiliation(s)
- Bohan Wang
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California.,Department of Urology, The Second Hospital, Zhejiang University, Hangzhou, China
| | - Jun Zhou
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Lia Banie
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Amanda B Reed-Maldonado
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Hongxiu Ning
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Zhihua Lu
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Yajun Ruan
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Tie Zhou
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Hsun Shuan Wang
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Byung Seok Oh
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Guifang Wang
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Stanley Lei Qi
- Department of Bioengineering, Stanford University, Stanford, California
| | - Guiting Lin
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
| | - Tom F Lue
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California
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