Osteogenic Matrix Cell Sheet Transplantation Enhances Early Tendon Graft to Bone Tunnel Healing in Rabbits

Inagaki, Yusuke; Uematsu, Kazuyoshi; Akahane, Manabu; Morita, Yusuke; Ogawa, Makoto; Ueha, Tomoyuki; Shimizu, Takamasa; Kura, Tomohiko; Kawate, Kenji; Tanaka, Yasuhito

doi:10.1155/2013/842192

Cited by 27 publications

(21 citation statements)

References 24 publications

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“…We previously developed a new technique of BMSC transplantation using osteogenic matrix cell sheets (OMCSs) derived from rat BMSCs to induce osteogenesis[ 7 ]. Because these OMCSs do not require a scaffold and maintain intercellular networks with the extracellular matrix that they produce, these sheets can be used in various graft sites in animal models[ 8 , 9 ]. Furthermore, these OMCSs produce growth factors, such as bone morphogenetic protein and vascular endothelial growth factor.…”

Section: Introductionmentioning

confidence: 99%

Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate: An experimental study in sheep

Kira¹,

Akahane²,

Omokawa³

et al. 2017

WJO

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AIMTo determine the effects of a cell sheet created from sheep bone marrow and tricalcium phosphate (TCP) on osteogenesis.METHODSBone marrow cells were harvested from a sheep and cultured in a minimal essential medium (MEM) containing ascorbic acid phosphate (AscP) and dexamethasone (Dex). After 2 wk, the formed osteogenic matrix cell sheet was lifted from the culture dish using a scraper. Additionally, harvested bone marrow cells were cultured in MEM only as a negative control group, and in MEM with AscP, Dex, and β-glycerophosphate as a positive control group. For in vitro evaluation, we measured the alkaline phosphatase (ALP) activity and osteocalcin (OC) content in the media of the cultured cells from each group. For in vivo analysis, a porous TCP ceramic was used as a scaffold. We prepared an experimental group comprising TCP scaffolds wrapped with the osteogenic matrix cell sheets and a control group consisting of the TCP scaffold only. The constructs were implanted subcutaneously into athymic rats and the cell donor sheep, and bone formation was confirmed by histology after 4 wk.RESULTSIn the in vitro part, the mean ALP activity was 0.39 ± 0.03 mg/well in the negative control group, 0.67 ± 0.04 mg/well in the sheet group, and 0.65 ± 0.07 mg/well in the positive control group. The mean OC levels were 1.46 ± 0.33 ng/well in the negative control group, 3.92 ± 0.16 ng/well in the sheet group, and 4.4 ± 0.47 ng/well in the positive control group, respectively. The ALP activity and OC levels were significantly higher in the cell sheet and positive control groups than in the negative control group (P < 0.05). There was no significant difference in ALP activity or OC levels between the cell sheet group and the positive control group (P > 0.05). TCP constructs wrapped with cell sheets prior to implantation showed bone formation, in contrast to TCP scaffolds alone, which exhibited poor bone formation when implanted, in the subcutaneous layer both in athymic rats and in the sheep.CONCLUSIONThis technique for preparing highly osteoinductive TCP may promote regeneration in large bone defects.

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Section: Introductionmentioning

confidence: 99%

Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate: An experimental study in sheep

Kira¹,

Akahane²,

Omokawa³

et al. 2017

WJO

Self Cite

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“…Pins have been used as an internal fixation material in studies for evaluation of effect of cell sheets on bone regeneration because more rigid fixation such as plates and screws could not be applied in experimental animals such as mice, rats and rabbits [15,[17][18][19][22][23][24]. The bone healing pathway by unstable fixation like pins is expected to be secondary bone healing due to cartilaginous callus formation however there is no primary bone healing through intramembranous ossification [25].…”

Section: Introductionmentioning

confidence: 99%

Different Bone Healing Effects of Undifferentiated and Osteogenic Differentiated Mesenchymal Stromal Cell Sheets in Canine Radial Fracture Model

Yoon

Khan

Choi

et al. 2017

Tissue Eng Regen Med

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Cell sheets technology is being available for fracture healing. This study was performed to clarify bone healing mechanism of undifferentiated (UCS) and osteogenic (OCS) differentiated mesenchymal stromal cell (MSC) sheets in the fracture model of dogs. UCS and OCS were harvested at 10 days of culture. Transverse fractures at the radius of six beagle dogs were assigned into three groups (n = 4 in each group) i.e. UCS, OCS and control. The fractures were fixed with a 2.7 mm locking plate and six screws. Cell sheets were wrapped around the fracture site. Bones were harvested 8 weeks after operation, then scanned by micro-computed tomography (micro-CT) and analyzed histopathologically. The micro-CT revealed different aspects of bone regeneration among the groups. The percentages of external callus volume out of total bone volume in control, UCS, and OCS groups were 42.1, 13.0 and 4.9% (p \ 0.05) respectively. However, the percentages of limbs having connectivity of gaps were 25, 12.5 and 75% respectively. In histopathological assessments, OCS group showed well organized and mature woven bone with peripheral cartilage at the fracture site, whereas control group showed cartilage formation without bone maturation or ossification at the fracture site. Meanwhile, fracture site was only filled with fibrous connective tissue without endochondral ossification and bone formation in UCS group. It was suggested that the MSC sheets reduced the quantity of external callus, and OCS induced the primary bone healing.

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“…Indeed, macrophage depletion after ACL reconstruction has been shown to promote healing at the tendon/bone interface 23 and transplantation of OMCS with grafted tendons in rabbits induced bone formation. 24 In addition, implantation of a bovine-derived bone tissue scaffold into a sheep rotor cuff model also enhanced regeneration of the tendon/bone interface. In particular, all four fibrocartilage zones at the interface were regenerated, resulting in a healed interface that was similar to the normal tendon/bone interface structure.…”

Section: Introductionmentioning

confidence: 99%

Kartogenin induces cartilage-like tissue formation in tendon–bone junction

Zhang

Wang

2014

Bone Res

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Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs.

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Osteogenic Matrix Cell Sheet Transplantation Enhances Early Tendon Graft to Bone Tunnel Healing in Rabbits

Cited by 27 publications

References 24 publications

Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate: An experimental study in sheep

Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate: An experimental study in sheep

Different Bone Healing Effects of Undifferentiated and Osteogenic Differentiated Mesenchymal Stromal Cell Sheets in Canine Radial Fracture Model

Kartogenin induces cartilage-like tissue formation in tendon–bone junction

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