A preliminary study of osteochondral regeneration using a scaffold-free three-dimensional construct of porcine adipose tissue-derived mesenchymal stem cells

Murata, Daiki; Tokunaga, Shigehiko; Tamura, Tadashi; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Fujiki, Makoto; Nakayama, Koichi; Misumi, Kazuhiro

doi:10.1186/s13018-015-0173-0

Cited by 78 publications

(94 citation statements)

References 39 publications

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“…of studies using the score (%)ReferencesHistology scores111 (100%)[49, 54–102, 134, 150–154, 160, 161, 272–324]International Cartilage Repair Society Score26 (23%)[49, 60, 61, 63, 66, 69, 72, 74, 79, 89, 92, 94, 98, 99, 272, 282, 283, 289, 305, 306, 310, 313, 314, 316, 319, 324]Wakitani score21 (19%)[58, 62, 67, 68, 72, 73, 80, 82, 97, 151, 273, 277, 279, 284, 285, 290, 299, 304, 310, 321]O’Driscoll score2018%[49, 71, 81, 84, 85, 93, 100, 160, 272, 276, 290, 296–298, 302, 306, 308, 313, 314, 322]Functional scores/mechanical11 (10%)[55, 57, 62, 67, 69, …”

Section: Resultsmentioning

confidence: 99%

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

et al. 2017

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BackgroundThe management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects.Main body of abstractThis review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous.Short conclusionsThis review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place.

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Section: Resultsmentioning

confidence: 99%

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

et al. 2017

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“…The histopathology of the implants after 6 months revealed active endochondral ossification underneath the smooth hyaline cartilage. After 12 months, not only the diminishing hyaline cartilage was as thick as the surrounding normal cartilage, but also a massive subchondral bone was present 39 .…”

Section: Cell Spheroids As Building Blocks For Bioprintingmentioning

confidence: 98%

“…invented the micro-needle based method 8,39,40 . It was called 'Kenzan' method, after the traditional art Ikebana, where for floral arrangements the stalks are impaled in a dome-shaped metal needle array called 'Kenzan' (in Japanese ken=sword; zan=mountain).…”

Section: The 'Kenzan' Methods Of Bioprintingmentioning

confidence: 99%

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

Moldovan

Hibino

Nakayama

2017

Tissue Engineering Part B: Reviews

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Abstract.Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live, de novo created bio-similar constructs. However, after more than a decade of incubation and many proofs-of-concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those which followed, were modified versions of the 3D printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, micro-extrusion or laser-assisted), this approach is material-('scaffold'-) dependent and energy-intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler, scaffoldfree bio-assembling methods. A substantial body of evidence has accumulated indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely 'print' spheroids has not been available until the invention of the microneedles-based ('Kenzan') spheroid assembling, and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel micro-needles ("kenzans') as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bio-engineering of tissues and organs.

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“…At least 3.0 × 10 7 autologous AT‐MSCs were used to fabricate each construct (Fig. A), as previously described . Briefly, cells were resuspended in SCM, and 1.0 × 10 4 cells/well were dispensed into thirty 96‐well plates with low cell adhesion properties (PrimeSurface 96U Plate; Sumitomo Bakelite, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…We previously designed and implemented an artificial scaffold‐free, three‐dimensional (3D) construct consisting of AT‐MSC aggregates (spheroids) that could elicit bone and cartilage regeneration at osteochondral defect sites in the knee joints of rabbits and pigs . However, especially in swine AT‐MSCs, constructs such as these are fragile and can be difficult to handle during surgical implantation, with the possibility of postsurgical defluxion.…”

mentioning

confidence: 99%

Osteochondral regeneration using constructs of mesenchymal stem cells made by bio three‐dimensional printing in mini‐pigs

Yamasaki

Kunitomi²,

Murata

et al. 2019

Journal Orthopaedic Research

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Osteoarthritis is a major joint disease that has been extensively investigated in humans and in model animals. In this study, we examined the regeneration of articular cartilage and subchondral bone using artificial scaffold‐free constructs composed of adipose tissue‐derived mesenchymal stem cells (AT‐MSCs) created using bio three‐dimensional (3D) printing with a needle‐array. Printed constructs were implanted into osteochondral defects created in the right femoral trochlear groove of six mini‐pigs, using femoral defects created in the left femurs as controls. Repair within the defects was evaluated at 3 and 6 months post‐implantation using computed tomography (CT) and magnetic resonance (MR) imaging. The radiolucent volume (RV, mm3) in the defects was calculated using multi‐planar reconstruction of CT images. MR images were evaluated based on a modified 2D‐ MOCART (magnetic resonance observation of cartilage repair tissue) grading system. Gross and microscopic pathology were scored according to the ICRS (International Cartilage Repair Society) scale at 6 months after implantation. The percentage RV at 3 months postoperation was significantly lower in the implanted defects than in the controls, whereas total scores based on the MOCART system were significantly higher in the implanted defects as compared with the controls. Although there were no statistical differences in the gross scores, the average histological scores were significantly higher in the implanted defects than in the controls. To our knowledge, this is the first report to suggest that artificial scaffold‐free 3D‐printed constructs of autologous AT‐MSCs can be aid in the osteochondral regeneration in pigs. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1398–1408, 2019.

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A preliminary study of osteochondral regeneration using a scaffold-free three-dimensional construct of porcine adipose tissue-derived mesenchymal stem cells

Cited by 78 publications

References 39 publications

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

Osteochondral regeneration using constructs of mesenchymal stem cells made by bio three‐dimensional printing in mini‐pigs

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