Recombinant Human FGF-2 for the Treatment of Early-Stage Osteonecrosis of the Femoral Head: TRION, a Single-Arm, Multicenter, Phase II Trial

Kuroda, Yutaka; Tanaka, Takeyuki; Miyagawa, Takaki; Hamada, Hirofumi; Abe, Hiroyasu; Ito‐Ihara, Toshiko; Asada, Ryuta; Fujimoto, Yusuke; Takahashi, Daisuke; Tetsunaga, Tomonori; Kaneuji, Ayumi; Takagi, Michiaki; Inaba, Yutaka; Morita, Satoshi; Sugano, Nobuhiko; Tanaka, Sakae; Matsuda, Shinya; Akiyama, Haruhiko

doi:10.2217/rme-2021-0049

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…Addressing this challenge, researchers have explored methods to establish sustained delivery systems for exosomes [48]. For instance, it has been demonstrated that incorporating FGF-2 into gelatin hydrogel enables long-term sustained release of FGF-2, thereby contributing to the improvement of ONFH [49,50]. Several studies have reported that encapsulating exosomes in hydrogels can maintain local concentration for long periods of time, thus providing therapeutic bene ts [47,51,52].…”

Section: Discussionmentioning

confidence: 99%

Exosomes secreted from human-derived adipose stem cells prevent progression of osteonecrosis of the femoral head

Ikezaki,

Kuroda,

Kawai

et al. 2024

Preprint

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Background Osteonecrosis of the femoral head (ONFH) primarily affects young individuals and is a leading cause of total hip arthroplasty in this population. Joint-preserving regenerative therapies involving core decompression (CD), enhanced with cells, growth factors, and bone substitutes, have been developed but lack extensive validation. Exosomes are emerging as a promising regenerative therapy. Human adipose stem cell (hADSC)-derived exosomes exhibit angiogenic and wound-healing effects on damaged and diseased tissues, suggesting their potential efficacy in treating early-stage ONFH. We aimed to investigate the efficacy of hADSC-derived exosomes based on CD in a medium-sized animal model (rabbit). Methods Exosomes were extracted using the ultrafiltration filter technique from the culture supernatants of two types of hADSCs. Characterization of exosomes was performed through nanoparticle tracking analysis, transmission electron microscopy, and the detection of specific biomarkers (CD9, CD63, and CD81) by western blotting. Eighteen rabbits underwent surgical vascular occlusion and intramuscular corticosteroid injections to induce ONFH. Concurrently, CD treatment with local administration of hADSC-derived exosomes (exosome group) or saline (control group) was performed. Femoral heads were harvested at 4, 8, and 12 weeks postoperatively and evaluated using micro-computed tomography and tissue staining to assess the protective effects on osteonecrosis, angiogenesis, and osteogenesis. Results Exosomes had average particle concentrations of 1.8×1012 or 1.8×109 particles/mL, with particle size distributions averaging 61.2 ± 14.7 or 123.1 ± 46.3 nm, and were confirmed by specific biomarkers. The exosome group exhibited a significant reduction in the severe progression of ONFH to stages 3 or 4 of the modified Ficat and Arlet classification, compared to the control group, which had four cases of stages 3 or 4. The exosome group showed significantly fewer empty lacunae in the subchondral bone area (p < 0.05) and significantly less articular cartilage injury (p < 0.05) compared to the corresponding in the control group. There were no significant differences in the microvessel number, bone trabecular structure, or volume of new bone in the medial region of the CD. Conclusions hADSC-derived exosomes can prevent the progression of ONFH by inhibiting osteonecrosis and cartilage damage. The ultrafiltration filter technique is effective for exosome extraction, indicating that exosomes hold potential as a therapeutic agent for ONFH.

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Section: Discussionmentioning

confidence: 99%

Exosomes secreted from human-derived adipose stem cells prevent progression of osteonecrosis of the femoral head

Ikezaki,

Kuroda,

Kawai

et al. 2024

Preprint

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“…Recombinant BMPs and fibroblast growth factor 2 (FGF-2) have been used for clinical application in combination with various carriers. [39][40][41][42][43] The therapeutic benefit of MSCs is known to be mostly attributable to factors they secrete. 44 In addition to growth factors and cytokines, cells communicate with neighbouring or distant cells via extracellular vesicles (EVs) including exosomes, which are EVs smaller than 150 nm in diameter.…”

Section: Delivery Of the Cellsmentioning

confidence: 99%

Regenerative medicine for osteonecrosis of the femoral head

2023

Bone & Joint Research

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“…With this important development in hand, tissues with a high donor demand, such as bone and cardiac, have taken advantage of this revolutionary multidisciplinary area and dealt with donor scarcity [1]. In addition, some of the studies have reached clinical trials, being proof of the capacity of designed systems to regenerate tissue [5][6][7]. Nonetheless, although tissue engineering has opened up a new way of practicing medicine, there are some concerns in terms of cost-effectiveness, reproducibility or scalability that need to be addressed [8].…”

Section: Introductionmentioning

confidence: 99%

Progress in Gelatin as Biomaterial for Tissue Engineering

et al. 2022

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Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a widely employed biomaterial in the field of tissue engineering: gelatin. Emerging techniques including 3D bioprinting and gelatin functionalization have demonstrated better mimicking of native tissue by reinforcing gelatin-based systems, among others. This breakthrough facilitates, on the one hand, the manufacturing process when it comes to practicality and cost-effectiveness, which plays a key role in the transition towards clinical application. On the other hand, it can be concluded that gelatin could be considered as one of the promising biomaterials in future trends, in which the focus might be on the detection and diagnosis of diseases rather than treatment.

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Recombinant Human FGF-2 for the Treatment of Early-Stage Osteonecrosis of the Femoral Head: TRION, a Single-Arm, Multicenter, Phase II Trial

Cited by 10 publications

References 40 publications

Exosomes secreted from human-derived adipose stem cells prevent progression of osteonecrosis of the femoral head

Exosomes secreted from human-derived adipose stem cells prevent progression of osteonecrosis of the femoral head

Regenerative medicine for osteonecrosis of the femoral head

Progress in Gelatin as Biomaterial for Tissue Engineering

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