Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis

Hsu, Chieh-Cheng; Cheng, Jai-Hong; Wang, Ching‐Jen; Ko, Jih‐Yang; Hsu, Shan-Ling; Hsu, Tsai-Chin

doi:10.3390/ijms21041217

Cited by 23 publications

(31 citation statements)

References 47 publications

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“…Further, SW therapy has been reported to promote mesenchymal stem cells (MSCs) proliferation and differentiation for tissue repairing [ 31 ]. All the evidence suggests that ADSCs combined with SW therapy may have the synergistic effects in the tissue regeneration [ 25 ]. In our study, the micro-CT analysis displayed that high-dose ADSCs and combined with SW therapy promote the bone healing more efficiently than other treatments ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…The source of the shockwave was a DUOLITH SD1 (STORZ MEDICAL AG, Tägerwilen, Switzerland). The focused shockwave was applied to the medial tibia condyle of the left knee at 0.5 cm below the joint line and 0.5 cm from the medial skin surface under ultrasound guidance [ 25 ]. Each rat knee received 800 impulses of shockwave at 0.25 mJ/mm 2 energy flux density and 4 Hz in a single session.…”

Section: Methodsmentioning

confidence: 99%

“…Many cellular signaling transductions have been reported to occur via the mechanotransduction caused by SW therapy, including the focal adhesion kinase (FAK), extracellular-signal-regulated kinase (ERK), Wnt/β-catenin, ATP/P2X7, and toll-like receptor 3 (TLR3) signaling pathways [ 23 , 24 ]. SW therapy has been proposed to be of significant potential for use in translational medicine and alternative therapy, or even in combination therapy for the treatment of a broad range of diseases [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, transplantation of high-dose autologous ADSCs combined with SW therapy was performed, which could synergistically ameliorate the process of inflammatory changes in the pathological deterioration of OA knees. The combination therapy was shown to contribute a greater benefit than the individual treatment along in knee OA [ 25 , 27 ]. Compilation of milestone discoveries related to autologous ADSCs combined with SW therapy should aid in further advancement in the field of cell biology and therapy towards clinical applications.…”

Section: Introductionmentioning

confidence: 99%

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Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint

et al. 2021

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Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint

et al. 2021

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“…Radial extracorporeal shockwave (r-ESW), an innovative and noninvasive therapy technique, has been widely used in treating various musculoskeletal diseases [1][2][3]. More encouragingly, as a specific mechanical stimulus form, r-ESW has gained increasing attention in regenerative medicine due to its mechanobiological effects on stem cells [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Radial extracorporeal shockwave promotes subchondral bone stem/progenitor cell self-renewal by activating YAP/TAZ and facilitates cartilage repair in vivo

Zhao

Wang

et al. 2021

Stem Cell Res Ther

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Background Radial extracorporeal shockwave (r-ESW), an innovative and noninvasive technique, is gaining increasing attention in regenerative medicine due to its mechanobiological effects. Subchondral bone stem/progenitor cells (SCB-SPCs), originating from the pivotal zone of the osteochondral unit, have been shown to have multipotency and self-renewal properties. However, thus far, little information is available regarding the influences of r-ESW on the biological properties of SCB-SPCs and their therapeutic effects in tissue regeneration. Methods SCB-SPCs were isolated from human knee plateau osteochondral specimens and treated with gradient doses of r-ESW in a suspension stimulation system. The optimized parameters for SCB-SPC self-renewal were screened out by colony-forming unit fibroblast assay (CFU-F). Then, the effects of r-ESW on the proliferation, apoptosis, and multipotency of SCB-SPCs were evaluated. Moreover, the repair efficiency of radial shockwave-preconditioned SCB-SPCs was evaluated in vivo via an osteochondral defect model. Potential mechanisms were explored by western blotting, confocal laser scanning, and high-throughput sequencing. Results The CFU-F data indicate that r-ESW could augment the self-renewal of SCB-SPCs in a dose-dependent manner. The CCK-8 and flow cytometry results showed that the optimized shockwave markedly promoted SCB-SPC proliferation but had no significant influence on cell apoptosis. Radial shockwave exerted no significant influence on osteogenic capacity but strongly suppressed adipogenic ability in the current study. For chondrogenic potentiality, the treated SCB-SPCs were mildly enhanced, while the change was not significant. Importantly, the macroscopic scores and further histological analysis strongly demonstrated that the in vivo therapeutic effects of SCB-SPCs were markedly improved post r-ESW treatment. Further analysis showed that the cartilage-related markers collagen II and proteoglycan were expressed at higher levels compared to their counterpart group. Mechanistic studies suggested that r-ESW treatment strongly increased the expression of YAP and promoted YAP nuclear translocation in SCB-SPCs. More importantly, self-renewal was partially blocked by the YAP-specific inhibitor verteporfin. Moreover, the high-throughput sequencing data indicated that other self-renewal-associated pathways may also be involved in this process. Conclusion We found that r-ESW is capable of promoting the self-renewal of SCB-SPCs in vitro by targeting YAP activity and strengthening its repair efficiency in vivo, indicating promising application prospects.

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Cell‐based therapies have disease‐modifying effects on osteoarthritis in animal models: A systematic review by the ESSKA Orthobiologic Initiative. Part 3: Umbilical cord, placenta, and other sources for cell‐based injectable therapies

Sourugeon,

Boffa,

Perucca Orfei

et al. 2024

Knee surg. sports traumatol. arthrosc.

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PurposeThis systematic review aimed to investigate in animal models the presence of disease‐modifying effects driven by non‐bone marrow‐derived and non‐adipose‐derived products, with a particular focus on umbilical cord and placenta‐derived cell‐based therapies for the intra‐articular injective treatment of osteoarthritis (OA).MethodsA systematic review was performed on three electronic databases (PubMed, Web of Science and Embase) according to PRISMA guidelines. The results were synthesised to investigate disease‐modifying effects in preclinical animal studies comparing injectable umbilical cord, placenta, and other sources‐derived products with OA controls. The risk of bias was assessed using the SYRCLE tool.ResultsA total of 80 studies were included (2314 animals). Cell therapies were most commonly obtained from the umbilical cord in 33 studies and placenta/amniotic tissue in 18. Cell products were xenogeneic in 61 studies and allogeneic in the remaining 19 studies. Overall, 25/27 (92.6%) of studies on umbilical cord‐derived products documented better results compared to OA controls in at least one of the following outcomes: macroscopic, histological and/or immunohistochemical findings, with 19/22 of studies (83.4%) show positive results at the cartilage level and 4/6 of studies (66.7%) at the synovial level. Placenta‐derived injectable products documented positive results in 13/16 (81.3%) of the studies, 12/15 (80.0%) at the cartilage level, and 2/4 (50.0%) at the synovial level, but 2/16 studies (12.5%) found overall worse results than OA controls. Other sources (embryonic, synovial, peripheral blood, dental pulp, cartilage, meniscus and muscle‐derived products) were investigated in fewer preclinical studies. The risk of bias was low in 42% of items, unclear in 49%, and high in 9% of items.ConclusionInterest in cell‐based injectable therapies for OA treatment is soaring, particularly for alternatives to bone marrow and adipose tissue. While expanded umbilical cord mesenchymal stem cells reported auspicious disease‐modifying effects in preventing OA progression in animal models, placenta/amniotic tissue also reported deleterious effects on OA joints. Lower evidence has been found for other cellular sources such as embryonic, synovial, peripheral blood, dental‐pulp, cartilage, meniscus, and muscle‐derived products.Level of EvidenceLevel II.

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Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis

Cited by 23 publications

References 47 publications

Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint

Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint

Radial extracorporeal shockwave promotes subchondral bone stem/progenitor cell self-renewal by activating YAP/TAZ and facilitates cartilage repair in vivo

Cell‐based therapies have disease‐modifying effects on osteoarthritis in animal models: A systematic review by the ESSKA Orthobiologic Initiative. Part 3: Umbilical cord, placenta, and other sources for cell‐based injectable therapies

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