scholarly journals Extracorporeal Shock Wave Rebuilt Subchondral Bone In Vivo and Activated Wnt5a/Ca2+ Signaling In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Lai Yu ◽  
Shuitao Liu ◽  
Zhe Zhao ◽  
Lin Xia ◽  
Haochong Zhang ◽  
...  
Keyword(s):  
Shock Wave ◽  
Subchondral Bone ◽  
Control Group ◽  
Extracorporeal Shock Wave ◽  
Tibial Condyle ◽  
Bone Changes ◽  
Marrow Mesenchymal Stem Cells ◽  
Ct Analysis

Background. This study aimed to identify the optimal extracorporeal shock wave (ESW) intensity and to investigate its effect on subchondral bone rebuilt in vivo and Wnt5a/Ca2+ signaling in vitro using an osteoarthritis (OA) rat model and bone marrow mesenchymal stem cells (BMMSCs), respectively. Methods. OA rats treated with (OA + ESW group) or without (OA group) ESW (n=12/group) were compared with healthy controls (control group, n=12). Gait patterns and subchondral trabecular bone changes were measured. Western blot and quantitative real-time polymerase chain reaction detected protein expression and gene transcription, respectively. Results. The gait disturbances of OA + ESW group were significantly improved compared with the OA group at 6th and 8th weeks. The micro-CT analysis indicated that the BMD, BSV/BV, BV/TV, Tr.S, and Tr.Th are significantly different between OA group and OA + ESW group. Expression of Wnt5a was increased rapidly after ESW treatment at 0.6 bar and peaked after 30 min. Conclusions. ESW were positive for bone remodeling in joint tibial condyle subchondral bone of OA rat. ESW prevented histological changes in OA and prevented gait disturbance associated with OA progression. Optimal intensity of ESW induced changes in BMMSCs via activation of the Wnt5a/Ca2+ signaling pathway.

scholarly journals Effect of extracorporeal shock wave therapy on equine umbilical cord blood mesenchymal stromal cells in vitro

2020 ◽  
Author(s):  
Ramés Salcedo-Jiménez ◽  
Judith Koenig ◽  
Olivia Lee ◽  
Thomas W.G. Gibson ◽  
Pavneesh Madan ◽  
...  
Keyword(s):  
Shock Wave ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Extracorporeal Shock Wave ◽  
Immunomodulatory Properties

AbstractExtracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells and decrease inflammatory and immune-reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation towards the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

scholarly journals Improved Healing of Diabetic Foot Ulcer upon Oxygenation Therapeutics through Oxygen-Loading Nanoperfluorocarbon Triggered by Radial Extracorporeal Shock Wave

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shunhao Wang ◽  
Chunyang Yin ◽  
Xiaoguang Han ◽  
Anyi Guo ◽  
Xiaodong Chen ◽  
...  
Keyword(s):  
Shock Wave ◽  
Drug Delivery ◽  
Diabetic Foot ◽  
Oxygen Affinity ◽  
Foot Ulcer ◽  
High Morbidity ◽  
Cavitation Effect ◽  
Extracorporeal Shock Wave

Diabetic foot ulcers (DFUs), the most serious complication of diabetes mellitus, can induce high morbidity, the need to amputate lower extremities, and even death. Although many adjunctive strategies have been applied for the treatment of DFUs, the low treatment efficiency, potential side effects, and high cost are still huge challenges. Recently, nanomaterial-based drug delivery systems (NDDSs) have achieved targeted drug delivery and controlled drug release, offering great promises in various therapeutics for diverse disorders. Additionally, the radial extracorporeal shock wave (rESW) has been shown to function as a robust trigger source for the NDDS to release its contents, as the rESW harbors a potent capability in generating pressure waves and in creating the cavitation effect. Here, we explored the performance of oxygen-loaded nanoperfluorocarbon (Nano-PFC) combined with the rESW as a treatment for DFUs. Prior to in vivo assessment, we first demonstrated the high oxygen affinity in vitro and great biocompatibility of Nano-PFC. Moreover, the rESW-responsive oxygen release behavior from oxygen-saturated Nano-PFC was also successfully verified in vitro and in vivo. Importantly, the wound healing of DFUs was significantly accelerated due to improved blood microcirculation, which was a result of rESW therapy (rESWT), and the targeted release of oxygen into the wound from oxygen-loaded Nano-PFC, which was triggered by the rESW. Collectively, the oxygen-saturated Nano-PFC and rESW provide a completely new approach to treat DFUs, and this study highlights the advantages of combining nanotechnology with rESW in therapeutics.

37 Healthy Foals Produced Using Bone Marrow-Mesenchymal Stem Cells as Nuclear Donors in Horse Cloning

2018 ◽  
Vol 30 (1) ◽  
pp. 158
Author(s):  
R. Olivera ◽  
L. Moro ◽  
R. Jordan ◽  
C. Luzzani ◽  
S. Miriuka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Donor Cell ◽  
Control Group ◽  
Nuclear Reprogramming ◽  
Marrow Mesenchymal Stem Cells

Somatic cell nuclear transfer efficiency is based on the capacity of the donor cell to be reset and reprogrammed to an embryonic state. So, the less differentiated the donor cells are, the more easily they could be reprogrammed by a recipient cytoplasm. Failures on appropriate nuclear reprogramming frequently lead to abnormalities associated with the placenta, umbilical cord, birthweight, and limbs. In the present study, we evaluated the efficiency of bone marrow mesenchymal stem cells (BM-MSC) compared with adult fibroblasts (AF) as nuclear donors in horse cloning and evaluated both in vitro and in vivo development of the embryos generated. Moreover, we focused on comparing the health of the foals generated and on the presence of anatomical abnormalities in foals produced from the different treatments. Embryos produced by AI, recovered by uterine flushing, and transferred to recipient mares were used as controls. All variables were analysed by Fisher test (P < 0.05). The cloning procedure was performed according to Olivera et al. (2016 PLoS One 11, e0164049, 10.1371/journal.pone.0164049). Both cleavage and blastocyst rates were higher when MSC were used as nuclear donors (P < 0.05). Cleavage rates were 85.6% (3875/4527) v. 90.2% (3095/3432) and blastocyst rates were 10.9% (492/4527) and 18.1% (622/3432) for AF and MSC groups, respectively. In the AF group, 476 blastocysts were transferred to recipient mares (232 transfers), and in the MSC group, 594 blastocysts were transferred 297 transfers). In the AI control group, 88 embryos were transferred. Pregnancies were diagnosed by transrectal ultrasonography 15 days after embryo transfer in all the groups. Pregnancy rates were similar between both cloning groups (41/232, 17.7% and 37/297, 12.5%for AF and MSC, respectively), but higher in the AI group (71/88, 80.7%). However, significant differences were observed in the birth of viable offsprings among the cloning groups. Despite similar rates of foal delivery (AF, 17/41, 41.5%; MSC, 21/37, 56.7%), a higher proportion of viable foals were obtained from the MSC group (20/37, 54.1%) compared with the AF group (9/41, 22%; P < 0.05). Surprisingly, as in the AI group (63/63, 100%), all of the viable foals obtained using MSC (20/20, 100%) were considered normal and did not show abnormalities associated with cloning. In contrast, in the AF group, only 4/9 (44.4%) were considered normal foals. The defects present in the other 5 foals were related to flexural and angular limb deformities and umbilical cord malformations. These were corrected rapidly with standard treatments or, in the case of the umbilical cords, minor surgery. This study shows for the first time that BM-MSC can be used as nuclear donors in horse cloning and that the foals obtained are as healthy as those produced by AI, showing no abnormalities related to deficiencies in nuclear reprogramming.

scholarly journals Extracorporeal Shock Wave Therapy Promotes Osteogenic Differentiation in a Rabbit Osteoporosis Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Baofeng Li ◽  
Renkai Wang ◽  
Xianyin Huang ◽  
Yongliang Ou ◽  
Zhenyu Jia ◽  
...  
Keyword(s):  
Shock Wave ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Detailed Mechanism ◽  
Extracorporeal Shock Wave ◽  
Osteoblast Maturation

Extracorporeal shock wave therapy (ESWT) has been identified to accelerate bone formation. However, detailed mechanism has not been fully explained. In this study, we found that ESWT promoted osteoblast formation in vitro. Local ESW treatment of femur increased bone formation in vivo. Furthermore, changing the density or frequency of energy, there was no statistical difference in osteogenic differentiation. Therapeutically, local ESW therapy relieved bone loss and increased the number of bone trabecular in a rabbit osteoporosis model and promoted endogenous levels of SMAD2 protein expression. Thus, ESWT may be a potential therapy by promoting osteoblast maturation through TGF-β/SMAD2 pathway.

scholarly journals Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells

2020 ◽  
Vol 7 ◽  
Author(s):  
Ramés Salcedo-Jiménez ◽  
Judith B. Koenig ◽  
Olivia J. Lee ◽  
Thomas W. G. Gibson ◽  
Pavneesh Madan ◽  
...  
Keyword(s):  
Shock Wave ◽  
Mesenchymal Stromal Cells ◽  
Metabolic Activity ◽  
Stromal Cells ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Extracorporeal Shock Wave ◽  
Immunomodulatory Properties

Extracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells, and decrease inflammatory and immune reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation toward the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

scholarly journals Napabucasin Induces Mouse Bone Loss by Impairing Bone Formation via STAT3

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiangru Huang ◽  
Anting Jin ◽  
Xijun Wang ◽  
Xin Gao ◽  
Hongyuan Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Loss ◽  
The Novel ◽  
Bone Homeostasis ◽  
Selective Targeting ◽  
Marrow Mesenchymal Stem Cells ◽  
Ct Analysis ◽  
Underlying Mechanisms

The novel small molecule Napabucasin (also known as BBI608) was shown to inhibit gene transcription driven by Signal Transducer and Activator of Transcription 3 (STAT3), which is considered a promising anticancer target. Many preclinical studies have been conducted in cancer patients examining the selective targeting of cancer stem cells by Napabucasin, but few studies have examined side effects of Napabucasin in the skeleton system. In the present study, we found treating bone marrow mesenchymal stem cells (BMSCs) with Napabucasin in vitro impaired their osteogenic differentiation. In terms of mechanisms, Napabucasin disrupted differentiation of BMSCs by inhibiting the transcription of osteogenic gene osteocalcin (Ocn) through STAT3. Moreover, through micro-CT analysis we found 4 weeks of Napabucasin injections induced mouse bone loss. Histological analysis revealed that Napabucasin-induced bone loss in mice was the result of impaired osteogenesis. In conclusion, this study provided evidence for the effect of Napabucasin on mouse bone homeostasis and revealed its underlying mechanisms in vivo and in vitro.

scholarly journals Sympathetic influences on articular cartilage regeneration capacity and osteoarthritis manifestation

2021 ◽  
Author(s):  
◽  
Karima El Bagdadi
Keyword(s):  
Subchondral Bone ◽  
Adrenergic Receptor ◽  
Cartilage Regeneration ◽  
Cartilage Degeneration ◽  
Bone Changes ◽  
Β2 Adrenergic Receptor ◽  
Deficient Mice

The pathogenesis of osteoarthritis (OA) involves articular cartilage, synovial tissue and subchondral bone and is therefore a disease of the whole joint. OA is characterized by progressive degradation of cartilage, synovial inflammation, osteophyte formation and subchondral bone sclerosis. Cartilage-surrounding tissues are innervated by tyrosine hydroxylase (TH)-positive sympathetic nerve fibers with the most important sympathetic neurotransmitter norepinephrine (NE) detected in the synovial fluid of OA patients. Furthermore, adrenergic receptors are expressed in different knee joint tissues. Most in vitro studies indicate a potential role of the β2-adrenergic receptor, which has been not investigated during OA pathogenesis in vivo. The role of the sympathetic nervous system (SNS) in OA progression has not yet been studied. Therefore, the objective of this study was to analyze how the SNS and NE influence the MSC dependent cartilage regeneration in vitro and the OA pathogenesis and manifestation in vivo. In the first part of this study, the effect of NE on the chondrogenesis of sASC, which are known to play an important role in cartilage regeneration was analyzed in vitro. In the second part of this study, the role of the SNS was studied in vivo in mice that were sympathectomized chemically followed by surgically induced OA. The specific focus was on the β2-adrenergic receptor effects on OA pathogenesis, which were analyzed in β2-adrenergic receptor-deficient mice. The in vitro experiments have shown that NE reduced the chondrogenic potential of sASCs by decreasing the expression of type II collagen and sGAG. NE mediated these effects mainly by the α2-AR signalling. Furthermore, NE treatment led to activation of the ERK1/2 signal pathway. These findings suggested that the sympathetic neurotransmitter NE might suppress the chondrogenic capacity of MSC and their dependent cartilage regeneration and may also play a role in OA progression and manifestation. The in vivo study has shown that sympathectomy reduced synovial TH-positive nerve fibers in the synovium and the NE concentration in the spleen significantly. In WT mice, DMM leads to increased NE concentrations in the spleen compared to sham mice indicating an increased SNS activity after mechanical stress or inflammation due to DMM. Sympathectomy leads to less pronounced cartilage degeneration (OARSI score) after DMM compared to DMM in WT mice. Furthermore, the release of the type II collagen degradation fragment CTX-II was abolished in Syx DMM mice compared to WT DMM mice, suggesting that less SNS activity due to sympathectomy reduced the cartilage degeneration during OA pathogenesis. Similarly, sympathectomy decreased the synovitis score significantly after DMM compared to DMM in WT mice. Synovitis in WT mice was accompanied by increased MMP-13 expression in the synovium after DMM, compared to Syx mice. Cartilage degeneration seemed to be driven mainly by the increased synovial inflammation accompanied by an increased MMP13 expression in synoviocytes and not in chondrocytes. The pathological changes in synovium and cartilage might also be linked to each other, as indicated by the moderate correlation between the synovial inflammation (synovitis score) and cartilage degeneration (OARSI score). Subchondral bone volume as well the thickness of the subchondral bone plate (SCBP) and calcified cartilage (CC) were increased in Syx mice compared to WT after DMM. The data on DMM induction in β2-AR deficient mice revealed that the β2-AR signaling is involved in cartilage degeneration and the aggravated subchondral bone changes as these mice had less pronounced cartilage degeneration compared to WT mice. While the cartilage degeneration was similar, the subchondral bone changes were more pronounced in β2-AR deficient mice compared to the Syx mice. Overall, the SNS had differential effects in cartilage, synovium and subchondral bone. A reduced SNS activity by sympathectomy attenuated cartilage degeneration and synovitis but aggravated the OA specific subchondral bone changes. These findings provide new insights into the development of novel therapeutic strategies for OA by targeting the SNS in a tissue- specific manner.

scholarly journals Extracorporeal Shock Wave Enhances the Cisplatin Efficacy by Improving Tissue Infiltration and Cellular Uptake in an Upper Urinary Tract Cancer Animal and Human-Derived Organoid Model

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4558
Author(s):  
Hao-Lun Luo ◽  
Hui-Ying Liu ◽  
Yin-Lun Chang ◽  
Yu-Li Su ◽  
Chun-Chieh Huang ◽  
...  
Keyword(s):  
Shock Wave ◽  
Urinary Tract ◽  
Combination Treatment ◽  
Shock Wave Lithotripsy ◽  
Synergistic Effects ◽  
Locally Advanced ◽  
Upper Urinary Tract ◽  
Extracorporeal Shock Wave

Upper urinary tract urothelial carcinoma (UTUC) is a relatively rare cancer with a poor prognosis if diagnosed at an advanced stage. Although cisplatin-based chemotherapy is a common treatment strategy, it has a limited response rate. Shock wave lithotripsy is a common treatment for upper urinary tract stones. Low-energy shock waves (LESWs) temporarily increase tissue permeability and enhance drug penetration to the targeted tissue. However, no study has investigated the efficacy of the combination of shock wave lithotripsy and chemotherapy in UTUC. Hence, in this study, we aimed to identify the potential application of the combination of LESW and chemotherapy in UTUC. We evaluated the synergistic effects of LESW and cisplatin in vitro, in vivo, and in patient-derived organoid (PDO) models. Compared with cisplatin alone, the combination treatment caused more significant tumour suppression in vitro and in animal models, without increased toxicity. Histological examination showed that compared with animals treated with cisplatin alone, those who received the combination treatment showed more deteriorated cell arrangement and cell oedema. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Thus, LESW combined with cisplatin is a potential new antitumour strategy for improving the treatment response in locally advanced UTUC.

In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Initial Value ◽  
Initial Rise ◽  
Biphasic Effect ◽  
Contrast Microscopy ◽  
Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

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