Mesenchymal Stem Cell Sheets Revitalize Nonviable Dense Grafts: Implications for Repair of Large-Bone and Tendon Defects

Ouyang, Hong; Cao, Tong; Zou, Xiao Hui; Heng, Boon Chin; Wang, Ling Ling; Xing, Song; Huang, He

doi:10.1097/01.tp.0000226232.79106.72

Cited by 83 publications

(85 citation statements)

References 15 publications

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“…in vivo, cell-sheet-scaffold/cell constructs formed bone via predominantly endochondral ossification when implanted under the skin of nude rats [103]. Ouyang et al [69] also reported a similar approach of using mesenchymal stem cell sheets to revitalize nonviable dense grafts and tendon. Using an ovine femoral model, Knothe Tate et al [48] used an in situ periosteal sleeve that was elevated circumferentially from diaphyseal bone to wrap around cortical bone chips.…”

Section: Functional Tissuementioning

confidence: 96%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

202

169

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Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.

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Section: Functional Tissuementioning

confidence: 96%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

202

169

View full text Add to dashboard Cite

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“…Meanwhile, GDF-5 has also been reported to increase mRNA expression of Col I and SCX in MSCs which are believed to be the markers of tendon/ligament differentiation (Farng et al 2008). Ouyang et al showed when assembled with frozen tendon graft in vitro, previously made MSCs sheets were wellincorporated within the tissue sheath around the tendon and adopted characteristic spindle-shaped morphology of tenocyte-like cells (Ouyang et al 2006). Distinctively, mechanical measures were more recommended for tenogenic differentiation of MSCs than other phenotypes of differentiation.…”

Section: Introductionmentioning

confidence: 99%

Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells

Luo

Song

et al. 2009

Cytotechnology

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Recent evidences have suggested that humoral factors released from the appropriate cocultured cells influenced the expansion and differentiation of mesenchymal stem cells (MSCs). However, little is known about the proliferation and differentiation of MSCs subjected to co-culture condition with tenocytes. In this study, we aimed to establish a coculture system of MSCs and tenocytes and investigate the proliferation and tendon/ligament related gene expression of MSCs. MTT assay was used to detect the expansion of MSCs. Semi-quantitative RT-PCR was performed to investigate the expression of proliferation associated c-fos gene and tendon/ligament related genes, including type I collagen (Col I), type III collagen (Col III), tenascin C and scleraxis. Significant increase in MSCs expansion was observed after 3 days of co-culture with tenocytes. The c-fos gene expression was found distinctly higher than for control group on day 4 and day 7 of co-culture. The mRNA expression of four tendon/ligament related genes was significantly up-regulated after 14 days of co-culture with tenocytes. Thus, our research indicates that indirect coculture with tenocytes promotes the proliferation and mRNA expression of tendon/ligament related genes in MSCs, which suggests a directed differentiation of MSCs into tendon/ligament.

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“…Tissue engineering and regenerative medicine have shown great promise in promoting bone repair using MSC sheets alone or in combination with implants wrapped in MSC sheets [13,24]. Compared with the traditional method of directly seeding cells in scaffolds, the cell sheet technique makes it possible to deliver a much larger number of cells for efficient tissue regeneration [9]. As a potent regulator of cell function and differentiation, the extracellular matrix (ECM) can be well-preserved during cell sheet fabrication, thereby enhancing osteoblastic differentiation and improving bone formation [25].…”

Section: Discussionmentioning

confidence: 99%

“…Compared with the traditional method of directly seeding cells in scaffolds, the cell sheet technique makes it possible to deliver a much larger number of cells for efficient tissue regeneration [9]. The cell sheet can be easily detached from the culture substrate using a cell-scraper, which enables the extracellular matrix and cell-cell interactions to remain intact as no enzymatic treatments are used.…”

mentioning

confidence: 99%

“…The cell sheet can be easily detached from the culture substrate using a cell-scraper, which enables the extracellular matrix and cell-cell interactions to remain intact as no enzymatic treatments are used. Recent studies have shown that the cell sheet technique is effective for the treatment of myocardial infarction [10], tendon defects [9] and periodontitis [11]. The cell sheet technique contributes to bone formation in cases of osseointegration [12], nonunion [13], various bone defects [14,15] and spinal interbody fusion [16].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Restoration of rat calvarial defects by poly(lactide-co-glycolide)/hydroxyapatite scaffolds loaded with bone mesenchymal stem cells and DNA complexes

Wang

Guo

et al. 2011

Chin. Sci. Bull.

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A composite construct comprising of a bone mesenchymal stem cell (BMSC) sheet, plasmid DNA, encoding human bone morphogenic protein-2 (hBMP-2), and poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) sponge was designed and employed in the restoration of rat calvarial defects. To improve gene transfection efficiency, a cationic chitosan derivative, N,N,N,-trimethyl chitosan chloride (TMC), was employed as the vector. The TMC/DNA complexes had a transfection efficiency of 13% in rat BMSCs, resulting in heterogeneous hBMP-2 expression in a 10-d culture period in vitro. In vivo culture of the composite constructs was performed by implantation into rat full-thickness calvarial defects, using constructs lacking pDNA-hBMP-2 or BMSC sheets as controls. Significantly higher heterogeneous expression of hBMP-2 was detected in vivo at 2 weeks for the cell sheet/DNA complex/scaffold constructs, compared with the constructs lacking pDNA-hBMP-2 or BMSC sheets. New bone formation was evident as early as 4 weeks in the experimental constructs. At 8 weeks, partial bridging of calvarial defects was observed in the experimental constructs, which was significantly better than the constructs lacking pDNA-hBMP-2 or BMSC sheets. Therefore, the combination of the PLGA/HA scaffold with BMSC sheets and gene therapy vectors is effective at enhancing bone formation.gene therapy, bone regeneration, bone marrow stem cells, poly(lactide-co-glycolide), BMP-2 Citation:Li D, Wang W, Guo R, et al. Restoration of rat calvarial defects by poly(lactide-co-glycolide)/hydroxyapatite scaffolds loaded with bone mesenchymal stem cells and DNA complexes.

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Mesenchymal Stem Cell Sheets Revitalize Nonviable Dense Grafts: Implications for Repair of Large-Bone and Tendon Defects

Abstract: The results therefore demonstrated that MSCs sheets are easily fabricated and can maintain their differentiation potential within particular scaffolds, which would suggest a novel and convenient strategy for revitalizing large tissue grafts to improve clinical outcome.

Cited by 83 publications

References 15 publications

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells

Restoration of rat calvarial defects by poly(lactide-co-glycolide)/hydroxyapatite scaffolds loaded with bone mesenchymal stem cells and DNA complexes

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