Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model

Kaibuchi, Nobuyuki; Iwata, Takanori; Yamato, Masayuki; Okano, Teruo; Ando, Tomohiro

doi:10.1016/j.actbio.2016.06.022

Cited by 69 publications

(71 citation statements)

References 58 publications

(79 reference statements)

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“…Since the therapeutic effect of cell therapy is thought to be derived from factors secreted from transplanted cells , it is generally believed that prolonged presence of donor cells in the target organs leads to improved efficacy. Indeed, the long‐term survival of the cell sheets on the target organ resulted in stronger therapeutic effects as compared with injection of cells in various disease models . Furthermore, we previously showed that transplantation of an HGF‐tg MC‐sheet onto the kidney surface suppressed kidney injury to a significantly greater degree than remote transplantation (on femoral vascular bed) of the HGF‐tg MC‐sheets .…”

Section: Discussionmentioning

confidence: 99%

“…Bone marrow cells were isolated from male Sprague‐Dawley (SD) rats for in vitro experiments, as well as from SD Tg (CAG‐enhanced green fluorescent protein [EGFP]) rats and Luc Tg Lewis rats , for in vivo experiments, as previously described . Briefly, after cutting the epiphyses of femora and tibiae, the bone marrow cavity was flushed with complete medium (a‐MEM; Minimum Essential Medium; Life Technologies, Carlsbad, CA, USA supplemented with 1% penicillin–streptomycin [Life Technologies, Rockville, MD, USA] and 10% fetal bovine serum [Japan BioSerum]), using a 23‐gauge needle.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were passaged at 80%–90% confluence using 0.05% trypsin‐ethylenediaminetetraacetic acid (Merck, Darmstadt, Germany) and expanded until passages 3–5. Cultured cells were evaluated for MSC characteristics according to the ability to differentiate into osteocytes and adipocytes, colony‐forming ability, and cell‐surface markers as previously described .…”

Section: Methodsmentioning

confidence: 99%

“…MSCs secrete various cytokines and repair injured organs through various mechanism, including vasoprotection, anti‐inflammation, and immunomodulation . Several studies reported the effect of MSC sheets under various conditions, including ischemic cardiac disease, diabetic foot ulcers, and osteonecrosis of the jaw . Therapeutic effects were partially explained by cytokines secreted from MSCs, and additionally, it was also revealed that transplanted MSCs migrated into the target organs and differentiated into mural cells.…”

Section: Introductionmentioning

confidence: 99%

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Rat Mesenchymal Stromal Cell Sheets Suppress Renal Fibrosis via Microvascular Protection

Imafuku

Oka

Miyabe

et al. 2019

Stem Cells Translational Medicine

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Renal fibrosis is one of the largest global health care problems, and microvascular (MV) injury is important in the development of progressive fibrosis. Although conventional cell therapy suppresses kidney injury via the role of vasoprotective cytokines, the effects are limited due to low retention of administered cells. We recently described that transplantation of hepatocyte growth factor (HGF)transgenic mesothelial cell sheets showed a remarkable cell survival and strong therapeutic effects in a rat renal fibrosis model. Due to the translational hurdles of transgenic cells, we here applied this technique for allogeneic transplantation using rat bone marrow mesenchymal stromal cells (MSCs). MSC sheets were transplanted onto the kidney surface of a rat renal ischemia-reperfusion-injury model and the effects were compared between those in untreated rats and those receiving intravenous (IV) administration of the cells. We found that donor-cell survival was superior in the cell sheet group relative to the IV group, and that the cell sheets secreted HGF and vascular endothelial growth factor (VEGF) up to day 14. Transplantation of cell sheets increased the expression of activated HGF/VEGF receptors in the kidney. There was no evidence of migration of transplanted cells into the kidney parenchyma. Additionally, the cell sheets significantly suppressed renal dysfunction, MV injury, and fibrosis as compared with that observed in the untreated and IV groups. Furthermore, we demonstrated that the MSC sheet protected MV density in the whole kidney according to threedimensional microcomputed tomography. In conclusion, MSC sheets strongly prevented renal fibrosis via MV protection, suggesting that this strategy represents a potential novel therapy for various kidney diseases. STEM CELLS TRANSLATIONAL MEDICINE 2019;8:1330-1341 SIGNIFICANCE STATEMENTCell therapy has been applied to various diseases that are resistant to conventional therapy. Renal fibrosis is one of the most difficult issues, and many researchers have tried intravascular administration of stem cells. The present study revealed that transplantation of mesenchymal stromal cell (MSC) sheets onto the kidney showed dramatic effects, including long-term cell survival, amelioration of kidney dysfunction, vasoprotection, and antifibrosis, compared with intravenous administration of MSCs. These results suggest that cell sheet technology improves the effects of cell therapy in various aspects. Therefore, cell sheet therapy could be a potential novel therapeutic approach for various kidney diseases in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rat Mesenchymal Stromal Cell Sheets Suppress Renal Fibrosis via Microvascular Protection

Imafuku

Oka

Miyabe

et al. 2019

Stem Cells Translational Medicine

View full text Add to dashboard Cite

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“…Cell‐based regenerative medicine, involving the transplantation of cells into patients, is a promising therapeutic strategy. Various cell transplantation methods have been investigated, including the injection of cell suspensions, the transplantation of fabricated tissues with biodegradable scaffolds, and the transplantation of cell sheets . Cell sheet transplantation has advantages compared with these other methods.…”

Section: Introductionmentioning

confidence: 99%

Local Release of VEGF Using Fiber Mats Enables Effective Transplantation of Layered Cardiomyocyte Sheets

Nagase

Nagumo

Kim

et al. 2017

Macromolecular Bioscience

Self Cite

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Cell sheet transplantation is a key tissue engineering technology. A vascular endothelial growth factor (VEGF)‐releasing fiber mat is developed for the transplantation of multilayered cardiomyocyte sheets. Poly(vinyl alcohol) fiber mats bearing poly(lactic‐co‐glycolic acid) nanoparticles that incorporate VEGF are fabricated using electrospinning and electrospray methods. Six‐layered cardiomyocyte sheets are transplanted with a VEGF‐releasing mat into athymic rats. After two weeks, these sheets produce thicker cardiomyocyte layers compared with controls lacking a VEGF‐releasing mat, and incorporate larger‐diameter blood vessels containing erythrocytes. Thus, local VEGF release near the transplanted cardiomyocytes induces vascularization, which supplies sufficient oxygen and nutrients to prevent necrosis. In contrast, cardiomyocyte sheets without a VEGF‐releasing mat do not survive in vivo, probably undergo necrosis, and are reduced in thickness. Hence, these VEGF‐releasing mats enable the transplantation of multilayered cardiomyocyte sheets in a single procedure, and should expand the potential of cell sheet transplantation for therapeutic applications.

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Biomimetic Tissue‐Engineered Bone Substitutes for Maxillofacial and Craniofacial Repair: The Potential of Cell Sheet Technologies

Kawecki

Clafshenkel

Fortin

et al. 2017

Adv Healthcare Materials

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Maxillofacial defects are complex lesions stemming from various etiologies: accidental, congenital, pathological, or surgical. A bone graft may be required when the normal regenerative capacity of the bone is exceeded or insufficient. Surgeons have many options available for bone grafting including the "gold standard" autologous bone graft. However, this approach is not without drawbacks such as the morbidity associated with harvesting bone from a donor site, pain, infection, or a poor quantity and quality of bone in some patient populations. This review discusses the various bone graft substitutes used for maxillofacial and craniofacial repair: allografts, xenografts, synthetic biomaterials, and tissue-engineered substitutes. A brief overview of bone tissue engineering evolution including the use of mesenchymal stem cells is exposed, highlighting the first clinical applications of adipose-derived stem/stromal cells in craniofacial reconstruction. The importance of prevascularization strategies for bone tissue engineering is also discussed, with an emphasis on recent work describing substitutes produced using cell sheet-based technologies, including the use of thermo-responsive plates and the self-assembly approach of tissue engineering. Indeed, considering their entirely cell-based design, these natural bone-like substitutes have the potential to closely mimic the osteogenicity, osteoconductivity, osteoinduction, and osseointegration properties of autogenous bone for maxillofacial and craniofacial reconstruction.

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Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model

Cited by 69 publications

References 58 publications

Rat Mesenchymal Stromal Cell Sheets Suppress Renal Fibrosis via Microvascular Protection

Rat Mesenchymal Stromal Cell Sheets Suppress Renal Fibrosis via Microvascular Protection

Local Release of VEGF Using Fiber Mats Enables Effective Transplantation of Layered Cardiomyocyte Sheets

Biomimetic Tissue‐Engineered Bone Substitutes for Maxillofacial and Craniofacial Repair: The Potential of Cell Sheet Technologies

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