Tissue‐engineered Approach for the Treatment of Steroid‐induced Osteonecrosis of the Femoral Head: Transplantation of Autologous Mesenchymal Stem Cells Cultured With Beta‐Tricalcium Phosphate Ceramics and Free Vascularized Fibula

Kawate, Kenji; Yajima, Hiroshi; Ohgushi, Hajime; Kotobuki, Noriko; Sugimoto, Kazuya; Ohmura, Tetsuji; Kobata, Yasunori; Shigematsu, Koji; Kawamura, Kenji; Tamai, Katsuya; Takakura, Yoshinori

doi:10.1111/j.1525-1594.2006.00333.x

Cited by 150 publications

(99 citation statements)

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“…Tissue-engineering approaches, including stem cells and growth factors [18,24] or externally applied signals such as stimulation with electric currents [7,11], ultrasound [10,43], or laser [28], are promising in overcoming these problems, but they also have several shortcomings. Current cell culture-based techniques require considerable resources to reach the number of required cells, bear risks for transfer of infectious diseases, and involve invasive surgery [40].…”

Section: Introductionmentioning

confidence: 99%

Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study

Hwang

Lublinsky

Seo

et al. 2008

Clin Orthop Relat Res

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High-frequency, low-magnitude accelerations can be anabolic and anticatabolic to bone. We tested the hypothesis that application of these mechanical signals can accelerate bone regeneration in scaffolded and nonscaffolded calvarial defects. The cranium of experimental rats (n = 8) in which the 5-mm bilateral defects either contained a collagen scaffold or were left empty received oscillatory accelerations (45 Hz, 0.4 g) for 20 minutes per day for 3 weeks. Compared with scaffolded defects in the untreated control group (n = 6), defects with a scaffold and subject to oscillatory accelerations had a 265% greater fractional bone defect area 4 weeks after the surgery. After 8 weeks of healing (1-week recovery, 3 weeks of stimulation, 4 weeks without stimulation), the area (181%), volume (137%), and thickness (53%) of the regenerating tissue in the scaffolded defect were greater in experimental than in control animals. In unscaffolded defects, mechanical stimulation induced an 84% greater bone volume and a 33% greater thickness in the defect. These data provide preliminary evidence that extremely low-level, high-frequency accelerations can enhance osseous regenerative processes, particularly in the presence of a supporting scaffold.

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Section: Introductionmentioning

confidence: 99%

Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study

Hwang

Lublinsky

Seo

et al. 2008

Clin Orthop Relat Res

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“…Cell-based treatments have advanced and have been applied for some diseases involving osteonecrosis and cartilage defects of joints (10,21,22). Recently, Kawate et al (10) applied constructs of MSCs and β-TCP ceramics to a clinical case of femoral head osteonecrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Kawate et al (10) applied constructs of MSCs and β-TCP ceramics to a clinical case of femoral head osteonecrosis. They reported that the osteonecrosis did not progress any further, and early bone regeneration was observed, indicating that such a cell-based tissue engineering strategy has potential for clinical application.…”

Section: Discussionmentioning

confidence: 99%

“…In bone tissue engineering research (6,8,9) and clinical cases (10), MSCs are generally seeded onto scaffolds, such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), in order to construct tissue engineered bone. However, osteogenic potential of the tissue engineered bone after transplantation in vivo can vary among the constructs (9).…”

Section: Introductionmentioning

confidence: 99%

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Cell Sheet Injection as a Technique of Osteogenic Supply

Akahane¹,

Ueha²,

Shimizu³

et al. 2010

Int J Stem Cells

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We previously reported a new cell transplantation method utilizing injections of mesenchymal stem cell (MSC) sheets that have osteogenic potential. After subcutaneous transplantation without any scaffold, the sheet demonstrated in vivo bone formation. In the present study, we transplanted such sheets by injection into implanted ceramics and assessed whether the injectable MSC sheets could stimulate osteogenic integration of the ceramics. To fabricate MSC sheets, bone marrow cells cultured from femur shafts of 7-week-old rats were subcultured in regular 10-cm dishes containing dexamethasone and ascorbic acid phosphate until confluent. Each cell sheet was then lifted using a scraper. Porous β-tricalcium phosphate (β-TCP) disks (5 mm Ф×2 mm) were transplanted subcutaneously into the backs of the rats. Immediately following implantation, the sheets were injected around the disks via a 16G needle (immediate group). Cell sheets were also injected into the remaining implanted disks 1 week after disk implantation (1-wk group). Four weeks following sheet injection, radiography and histology revealed calcification and bone tissue around the harvested disks of the immediate group (eight disks exhibited bone formation/eight implanted disks), whereas calcification and bone tissue were observed in 50% of the samples in the 1-wk group (four disks exhibited bone formation/eight implanted disks). The present study indicates that injected cell sheets can supply osteogenic potential to implanted ceramics. Owing to the usage of a needle for cell sheet transplantation, such an injection method can be applied as a minimally invasive technique of osteogenic supply to implanted ceramics.

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“…Clinical applications of tissue engineered BMSCs have been attempted in a number of therapies, including the treatment of osteonecrosis [19][20][21]. In these appro-aches, BMSCs are obtained from the patients, following which they generally need to be expanded by serial passaging in vitro as the number of cells generated in primary culture is limited.…”

Section: Introductionmentioning

confidence: 99%

Increased osteogenesis with hydroxyapatite constructs combined with serially-passaged bone marrow-derived mesenchymal stem cells

Akahane

Ueha²,

Shimizu³

et al. 2012

SCD

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We have previously reported on both the osteogenic potential of hydroxyapatite (HA) combined with bone marrow-derived mesenchymal stem cells (BMSCs) and a method involving osteogenic matrix cell sheet transplantation of BMSCs. In the present study, we assessed the osteogenic potential of serially-passaged BMSCs, both in vitro and in vivo. We also assessed whether an additional cell-loading technique can regain the osteogenic potential of the constructs combined with serially-passaged BMSCs. The present study revealed that passage (P) 1 cells cultured in osteogenic-induced medium showed strong positive staining for alkaline phosphatase (ALP) and Alizarin Red S, whereas P3 cells showed faint staining for ALP, with no Alizarin Red S staining. Staining of P1, P2 and P3 cells were progressively weaker, indicating that the osteogenic potential of the serially-passaged rat BMSCs is lost after P3 in vitro. The in vivo study showed that little bone formation was observed in the HA constructs seeded with P3 cells, 4 weeks after subcutaneous implantation. However, P3 cell/HA constructs which had increased cell-loading showed abundant bone formation within the pores of the HA construct. ALP and osteocalcin mRNA expression in these constructs was significantly higher than that of constructs with regular cell-seeding. The present study indicates that the osteogenic potential of the constructs with serially-passaged BMSCs is increased by additional cell-loading. This method can be applied to cases requiring hard tissue reconstruction, where BMSCs require serial expansion of cells.

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Tissue‐engineered Approach for the Treatment of Steroid‐induced Osteonecrosis of the Femoral Head: Transplantation of Autologous Mesenchymal Stem Cells Cultured With Beta‐Tricalcium Phosphate Ceramics and Free Vascularized Fibula

Cited by 150 publications

References 9 publications

Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study

Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study

Cell Sheet Injection as a Technique of Osteogenic Supply

Increased osteogenesis with hydroxyapatite constructs combined with serially-passaged bone marrow-derived mesenchymal stem cells

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