Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells

Ando, Wataru; Tateishi, Kosuke; Hart, David A.; Katakai, Daisuke; Tanaka, Yoshinari; Nakata, Ken; Hashimoto, Jun; Fujie, Hiromichi; Shino, Konsei; Yoshikawa, Hideki; Nakamura, Norimasa

doi:10.1016/j.biomaterials.2007.08.030

Cited by 219 publications

(222 citation statements)

References 26 publications

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“…By day 38, the difference was insignificant as the interface now consisted entirely of new ECM, which was compositionally the same on both scaffolds. Furthermore, these constructs displayed equilibrium coefficients of friction that were similar to those of native cartilage, as well as other engineered cartilage constructs, by day 38 (40)(41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 74%

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

Moutos

Glass

Compton

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

102

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Biological resurfacing of entire articular surfaces represents an important but challenging strategy for treatment of cartilage degeneration that occurs in osteoarthritis. Not only does this approach require anatomically sized and functional engineered cartilage, but the inflammatory environment within an arthritic joint may also inhibit chondrogenesis and induce degradation of native and engineered cartilage. The goal of this study was to use adult stem cells to engineer anatomically shaped, functional cartilage constructs capable of tunable and inducible expression of antiinflammatory molecules, specifically IL-1 receptor antagonist (IL-1Ra). Large (22-mm-diameter) hemispherical scaffolds were fabricated from 3D woven poly(ε-caprolactone) (PCL) fibers into two different configurations and seeded with human adipose-derived stem cells (ASCs). Doxycycline (dox)-inducible lentiviral vectors containing eGFP or IL-1Ra transgenes were immobilized to the PCL to transduce ASCs upon seeding, and constructs were cultured in chondrogenic conditions for 28 d. Constructs showed biomimetic cartilage properties and uniform tissue growth while maintaining their anatomic shape throughout culture. IL-1Ra–expressing constructs produced nearly 1 µg/mL of IL-1Ra upon controlled induction with dox. Treatment with IL-1 significantly increased matrix metalloprotease activity in the conditioned media of eGFP-expressing constructs but not in IL-1Ra–expressing constructs. Our findings show that advanced textile manufacturing combined with scaffold-mediated gene delivery can be used to tissue engineer large anatomically shaped cartilage constructs that possess controlled delivery of anticytokine therapy. Importantly, these cartilage constructs have the potential to provide mechanical functionality immediately upon implantation, as they will need to replace a majority, if not the entire joint surface to restore function.

show abstract

Section: Discussionmentioning

confidence: 74%

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

Moutos

Glass

Compton

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

102

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“…They found TGF-b-induced cells to show significantly greater collagen II expression and a nonsignificant trend toward a better histological score. Ando et al 22 examined the effect of BMP on MSC differentiation and found this treatment also to increase cell expression of collagen II. However, the BMP comparison was an in vitro experiment, and the Ando study used only untreated, undifferentiated cells in the accompanying in vivo experiment.…”

Section: Mesenchymal Stem Cells Repair Cartilagementioning

confidence: 99%

“…No power analysis was done, although the animal number used was larger than that of a previously published, similar study. 22 Only histological and compressive stiffness data were collected, and functional benefit and the biochemical properties of the restored tissue were not examined. The histological analysis included only H&E staining and we did not stain for collagen II, collagen X, etc.…”

Section: Mesenchymal Stem Cells Repair Cartilagementioning

confidence: 99%

Tissue engineering‐based cartilage repair with mesenchymal stem cells in a porcine model

Chang

Kuo

Lin

et al. 2011

Journal Orthopaedic Research

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This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor b (TGF-b) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-b-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-b-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-b-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. ß

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“…1,2 One critical obstacle in this promising field is vascularization of the engineered tissues. The most successful applications of tissue engineering to date have been limited to thin (<2 mm) avascular tissues, such as skin 3 and cartilage, 4 in which delivery of nutrients and oxygen occurs by diffusion. Before the establishment of blood flow, cells in the inner portion of an implanted tissue are exposed to an environment with minimal oxygen and nutrients, which can lead to significant cell death.…”

Section: Introductionmentioning

confidence: 99%

Rapid Anastomosis of Endothelial Progenitor Cell–Derived Vessels with Host Vasculature Is Promoted by a High Density of Cotransplanted Fibroblasts

Chen

Aledia

Popson

et al. 2010

Tissue Engineering Part A

183

193

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To ensure survival of engineered implantable tissues thicker than approximately 2-3 mm, convection of nutrients and waste products to enhance the rate of transport will be required. Creating a network of vessels in vitro, before implantation (prevascularization), is one potential strategy to achieve this aim. In this study, we developed three-dimensional engineered vessel networks in vitro by coculture of endothelial cells (ECs) and fibroblasts in a fibrin gel for 7 days. Vessels formed by cord blood endothelial progenitor cell-derived ECs (EPC-ECs) in the presence of a high density of fibroblasts created an interconnected tubular network within 4 days, compared with 5-7 days in the presence of a low density of fibroblasts. Vessels derived from human umbilical vein ECs (HUVECs) in vitro showed similar kinetics. Implantation of the prevascularized tissues into immunecompromised mice, however, revealed a dramatic difference in the ability of EPC-ECs and HUVECs to form anastomoses with the host vasculature. Vascular beds derived from EPC-ECs were perfused within 1 day of implantation, whereas no HUVEC vessels were perfused at day 1. Further, while almost 90% of EPC-EC-derived vascular beds were perfused at day 3, only one-third of HUVEC-derived vascular beds were perfused. In both cases, a high density of fibroblasts accelerated anastomosis by 2-3 days. We conclude that both EPC-ECs and a high density of fibroblasts significantly accelerate the rate of functional anastomosis, and that prevascularizing an engineered tissue may be an effective strategy to enhance convective transport of nutrients in vivo.

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Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells

Cited by 219 publications

References 26 publications

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

Tissue engineering‐based cartilage repair with mesenchymal stem cells in a porcine model

Rapid Anastomosis of Endothelial Progenitor Cell–Derived Vessels with Host Vasculature Is Promoted by a High Density of Cotransplanted Fibroblasts

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