Low intensity pulsed ultrasound enhances bone marrow-derived stem cells-based periodontal regenerative therapies

To investigate how a back propagation neural network based on genetic algorithm (GA-BPNN) optimizes the low-intensity pulsed ultrasound (LIPUS) stimulation parameters to improve the bone marrow mesenchymal stem cells (BMSCs) viability further. The LIPUS parameters were set at various frequencies (0.6, 0.8, 1.0, and 1.2 MHz), voltages (5, 6, 7, and 8 V), and stimulation durations (3, 6, and 9 minutes). As only some discrete points can be set up in the experiments, the optimal LIPUS stimulation parameter may not be in the value of these settings. The GA-BPNN algorithm is used to optimize parameters of LIPUS to increase the BMSCs viability further. The BMSCs viability of the LIPUS-treated group was improved up to 19.57% (P<0.01). With the optimization via the GA-BPNN algorithm, the viability of BMSCs was further improved by about 5.36% (P<0.01) under the optimized condition of 6.92 V, 1.02 MHz, and 7.3 min. LIPUS is able to improve the BMSCs viability, which can be improved further by LIPUS with parameter optimization via GA-BPNN algorithm.

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Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Preconditioned by Low-Intensity Pulsed Ultrasound Stimulation Promote Bone-Tendon Interface Fibrocartilage Regeneration and Ameliorate Rotator Cuff Fatty Infiltration

10.21203/rs.3.rs-809653/v1 ◽

2021 ◽

Author(s):

Bing Wu ◽

Huabin Chen ◽

Xin Shi ◽

Lingfeng Wang ◽

Tao Zhang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Rotator Cuff ◽

Fatty Infiltration ◽

Supraspinatus Tendon ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Ultrasound Stimulation

Abstract Fibrovascular scar healing of bone-tendon interface (BTI) instead of functional fibrocartilage regeneration is the main concern associated with unsatisfactory prognosis in rotator cuff repair. Mesenchymal stem cells exosomes have been reported to be a new promising cell-free approach for rotator cuff healing. Whereas, controvercies abound in whether exosomes of native MSCs alone can effectively induce chondrogenesis. In this study, we aimed to explore the effect of Exosomes derived from low-intensity pulsed ultrasound stimulation (LIPUS)-preconditioned bone marrow mesenchymal stem cells (LIPUS-BMSC-Exos) or un-preconditioned BMSCs (BMSC-Exos) on rotator cuff healing and the underlying mechanism. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to saline, BMSCs-Exos or LIPUS-BMSC-Exos injection therapy. The results indicated that the biomechanical properties of the supraspinatus tendon-humeral junction were significantly improved in the LIPUS-BMSC-Exos group than that of the BMSCs-Exos group. The LIPUS-BMSC-Exos group also exhibited a higher histological score and more newly regenerated fibrocartilage at the repair site at postoperative 2 and 4 weeks and less fatty infiltration at 4 weeks than the BMSCs-Exos group. In vitro, co-culture of BMSCs with LIPUS-BMSC-Exos could significantly promote BMSCs chondrogenic differentiation and inhibit adipogenic differentiation than the BMSCs and BMSC-Exos co-cultured group did. Subsequently, quantitative real-time polymerase chain reaction revealed significantly higher enrichment of chondrogenic miRNAs and less enrichment of adipogenic miRNAs in LIPUS-BMSC-Exos compared with BMSC-Exos. Moreover, we demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-140, one of the most abundant miRNAs in LIPUS-BMSC-Exos. Collectively, our results highlight the regenerative potential of LIPUS-BMSC-Exos to promote BTI fibrocartilage regeneration and ameliorate supraspinatus fatty infiltration by positive regulation of pro-chondrogenetic and anti-adipogenetic of BMSCs differentiation which was primarily through delivering miR-140.

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TGF-β1-induced chondrogenesis of bone marrow mesenchymal stem cells is promoted by low-intensity pulsed ultrasound through the integrin-mTOR signaling pathway

Stem Cell Research & Therapy ◽

10.1186/s13287-017-0733-9 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 20

Author(s):

Peng Xia ◽

Xiaoju Wang ◽

Yanping Qu ◽

Qiang Lin ◽

Kai Cheng ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Signaling Pathway ◽

Mtor Signaling Pathway ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Marrow Mesenchymal Stem Cells ◽

Tgf Β1

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Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation

Stem Cells International ◽

10.1155/2020/8863577 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Rong Zhang ◽

Zhaoling Wang ◽

Guoxiong Zhu ◽

Gaoyi Wu ◽

Qingyuan Guo ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cell Viability ◽

Osteogenic Differentiation ◽

Pulsed Ultrasound ◽

Differentiation Capacity ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Marrow Mesenchymal Stem Cells

Osteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this study, the effects of LIPUS on cytoskeletal reorganization, cell viability, and osteogenic differentiation capacity of rat mandible-derived bone marrow mesenchymal stem cells (M-BMMSCs) induced by radiation were determined by immunofluorescence staining, CCK-8 cell proliferation assay, quantification of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time RT-PCR, respectively. Moreover, the involvement of the RhoA/ROCK signaling pathway underlying this process was investigated via western blot analysis. We found that radiation induced significant damage to the cytoskeleton, cell viability, and osteogenic differentiation capacity of M-BMMSCs and downregulated their expression of RhoA, ROCK, and vinculin while increasing FAK expression. LIPUS treatment effectively rescued the disordered cytoskeleton and redistributed vinculin. Furthermore, the cell viability and osteogenic differentiation capacity were also significantly recovered. More importantly, it could reverse the aberrant expression of the key molecules induced by radiation. Inhibition of RhoA/ROCK signaling remarkably aggravated the inhibitory effect of radiation and attenuated the therapeutic effect of LIPUS. In the light of these findings, the RhoA/ROCK signaling pathway might be a promising target for modifying the therapeutic effect of LIPUS on osteoradionecrosis.

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