In vivo cell tracking by bioluminescence imaging after transplantation of bioengineered cell sheets to the knee joint

Takaku, Yuko; Murai, Kunihiko; Ukai, Taku; Ito, Satoshi; Kokubo, Mami; Satoh, Masaaki; Kobayashi, Eiji; Yamato, Masayuki; Okano, Teruo; Takeuchi, Mamoru; Mochida, Joji; Sato, Masato

doi:10.1016/j.biomaterials.2013.11.071

Cited by 44 publications

(43 citation statements)

References 28 publications

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“…Hyaline cartilage regeneration induced by chondrocyte sheet transplantation has been confirmed in animal models of cartilage defects [1], [2], [3], [4]. Based on these results, we have conducted a clinical study using autologous knee chondrocyte sheets in patients with cartilage defects in the knee joint, including osteoarthritis patients.…”

Section: Introductionmentioning

confidence: 90%

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Toyoda

Sato

Takahashi

et al. 2019

Regenerative Therapy

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IntroductionCartilage regeneration is a promising therapy for restoring joint function in patients with cartilage defects. The limited availability of autologous chondrocytes or chondrogenic progenitor cells is an obstacle to its clinical application. We investigated the existence and chondrogenic potential of synovial membrane-derived multilineage-differentiating stress-enduring (Muse)-like cells as an alternative cell source for cartilage regeneration.MethodsCells positive for stage-specific embryonic antigen-3 (SSEA-3), a marker of Muse cells, were isolated from the synovial membranes of 6 of 8 patients (median age, 53.5 years; range 36–72 years) by fluorescence-activated cell sorting. SSEA-3-positive cells were cultured in methylcellulose to examine their ability to form Muse clusters that are similar to the embryoid bodies formed by human embryonic stem cells. Muse clusters were expanded and chondrogenic potential of M-cluster-derived MSCs examined using a pellet culture system. Chondrogenic differentiation was evaluated by proteoglycan, safranin O, toluidine blue and type II collagen staining. To evaluate the practicality of the procedure for isolating Muse-like cells, we compared chondrogenic potential of M-cluster derived MSCs with expanded cells derived from the clusters formed by unsorted synovial cells.ResultsSynovial membranes contained SSEA-3-positive cells that after isolation exhibited Muse-like characteristics such as forming clusters that expressed NANOG, OCT3/4, and SOX2. In the pellet culture system, cell pellets created from the M-cluster-derived MSCs exhibited an increase in wet weight, which implied an increase in extracellular matrix production, displayed metachromasia with toluidine blue and safranin O staining and were aggrecan-positive and type II collagen-positive by immunostaining. Unsorted synovial cells also formed clusters in methylcellulose culture, and the expanded cell population derived from them exhibited chondrogenic potential. The histological and immunohistochemical appearance of chondrogenic pellet created from unsorted synovial cell-derived cells were comparable with that from M-cluster-derived MSCs.ConclusionsMuse-like cells can be isolated from the human synovial membrane, even from older patients, and therefore may provide a source of multipotent cells for regenerative medicine. In addition, the cluster-forming cell population within synovial cells also has excellent chondrogenic potential. These cells may provide a more practical option for cartilage regeneration.

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Section: Introductionmentioning

confidence: 90%

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Toyoda

Sato

Takahashi

et al. 2019

Regenerative Therapy

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“…In the case of transplanted chondrocytes as a cell sheet, it was reported that the transplanted cells survived and could be detected for more than 21 months by in vivo imaging. 32 In this study, cell tracking experiments using GFP transgenic rats revealed that the regenerated hyaline cartilage-like tissues consisted largely of cells derived from the transplanted chondrocyte sheets. We suspect that differences in differentiation capacity between the chondrocyte sheets and synovial cell sheets as a cell source could be responsible for the difference in the effects of these cell sheets on cartilage repair.…”

Section: Figmentioning

confidence: 79%

Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet

Shimizu

Kamei

Adachi

et al. 2015

Tissue Engineering Part A

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Cell sheet engineering has developed as a remarkable method for cell transplantation. In the field of cartilage regeneration, several studies previously reported that cartilage defects could be regenerated by transplantation of a chondrocyte sheet using cell sheet engineering. However, it remains unclear how such a thin cell sheet could repair a deep cartilage defect. We, therefore, focused on the mechanism of cartilage repair using cell sheet engineering in this study. Chondrocyte sheets and synovial cell sheets were fabricated using cell sheet engineering, and these allogenic cell sheets were transplanted to cover an osteochondral defect in a rat model. Macroscopic and histological evaluation was performed at 4 and 12 weeks after transplantation. Analysis of the gene expression of each cell sheet and of the regenerated tissue at 1 week after transplantation was performed. In addition, green fluorescent protein (GFP) transgenic rats were used as donors (transplanted chondrocyte sheets) or recipients (osteochondral defect models) to identify the cell origin of regenerated cartilage.Cartilage repair was significantly better in the group implanted with a chondrocyte sheet than in that with a synovial cell sheet. The results of gene expression analysis suggest that the possible factor contributing to cartilage repair might be TGFb1. Cell tracking experiments using GFP transgenic rats showed that the regenerated cartilage was largely composed of cells derived from the transplanted chondrocyte sheets.

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“…33 BLI procedures possess several advantages for tissue engineering applications, including long term expression up to 21 months 113 and enhanced signal-to-noise ratio due to low intrinsic bioluminescence in mammalian tissues. 34 Two of the most common bioluminescent transgenic reporters are firefly luciferase ( Photinus pyralis ) and renilla luciferase ( Renilla reniformis) .…”

Section: In Vivo Characterization Of Biomaterials For Bone and Cmentioning

confidence: 99%

“…Both reporters have been used for bone and cartilage tissue engineering to monitor and quantify cell migration, distribution, and proliferation in ectopic and orthotopic sites. 34, 79, 90, 113 Through reporter design with specific osteogenic or chondrogenic markers and dual bioluminescence labeling, cell differentiation through the changes in gene expression patterns can also be elucidated. 11, 119 A detailed discussion of BLI transgenic reporters and potential applications specifically for bone tissue engineering can be found in other reviews.…”

Section: In Vivo Characterization Of Biomaterials For Bone and Cmentioning

confidence: 99%

“…Additionally, the bioluminescence intensity can be affected by tissue ingrowth into scaffolds and the scaffold material, 2 and altered by the defect model 11, 34 and method of luciferin administration (intravenous, subcutaneous, or intra-articular). 113 Other considerations include the fact that since BLI requires living cells for light emission, implants post-harvest cannot be imaged with bioluminescence, and the transplanted cell population must be easily passaged without losing phenotype in order to obtain a homogenous bioluminescence expression.…”

Section: In Vivo Characterization Of Biomaterials For Bone and Cmentioning

confidence: 99%

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Pre-clinical Characterization of Tissue Engineering Constructs for Bone and Cartilage Regeneration

Trachtenberg

Mikos

2014

Ann Biomed Eng

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Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth.

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In vivo cell tracking by bioluminescence imaging after transplantation of bioengineered cell sheets to the knee joint

Cited by 44 publications

References 28 publications

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet

Pre-clinical Characterization of Tissue Engineering Constructs for Bone and Cartilage Regeneration

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