Transplantation of human-induced pluripotent stem cells carried by self-assembling peptide nanofiber hydrogel improves bone regeneration in rat calvarial bone defects

Hayashi, Kamichika; Ochiai-Shino, Hiromi; Shiga, T; Onodera, Shin; Saito, Akiko; Shibahara, Takahiko

doi:10.1038/bdjopen.2015.7

Cited by 37 publications

(25 citation statements)

References 36 publications

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“…After anesthesia induction with 4% sevoflurane (Maruishi Pharmaceutical Co. Ltd., Osaka, Japan) inhalation, the rats were further anesthetized by intraperitoneal injection with sodium pentobarbital (30 mg/kg body weight; somnopentyl; Kyoritsu Seiyaku, Tokyo, Japan). Rat calvarial bone defects were created as previously described [ 27 ]. Scaffold/iPSC-derived OB complex was injected into the bone defect.…”

Section: Methodsmentioning

confidence: 99%

“…Microcomputed tomography (CT) parameters were as follows: X-ray source, 90 kV/100 μA; rotation, 360°; exposure time, 17 s; and voxel size, 50 × 50 × 50 μm (R-μCT®; Rigaku Corporation, Tokyo, Japan). CT images were compiled and three-dimensional images were rendered using the TRI/3D-BON system (Ratoc System Engineering Co. Ltd., Tokyo, Japan) as described previously [ 27 ]. Coronal sections (thickness = 5 μm) through the center of each circular defect were prepared and Villanueva–Goldner (V–G) staining [ 28 ] was performed.…”

Section: Methodsmentioning

confidence: 99%

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Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model

et al. 2018

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BackgroundRunt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models.MethodsTwo cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis.ResultsMutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect.ConclusionsTaken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0754-4) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model

et al. 2018

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“…These pluripotent cells have the ability to differentiate into any cell in the body and hold great promise in regenerative medicine as well as the treatment of intractable diseases. iPS cells have also been examined for their use in cell-seeded scaffolds for bone regeneration [96,97].…”

Section: Biodegradable Scaffolds As Drug Delivery Systemsmentioning

confidence: 99%

Biodegradable Polymers as Drug Delivery Systems for Bone Regeneration

Aoki

2020

Pharmaceutics

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Regenerative medicine has been widely researched for the treatment of bone defects. In the field of bone regenerative medicine, signaling molecules and the use of scaffolds are of particular importance as drug delivery systems (DDS) or carriers for cell differentiation, and various materials have been explored for their potential use. Although calcium phosphates such as hydroxyapatite and tricalcium phosphate are clinically used as synthetic scaffold material for bone regeneration, biodegradable materials have attracted much attention in recent years for their clinical application as scaffolds due their ability to facilitate rapid localized absorption and replacement with autologous bone. In this review, we introduce the types, features, and performance characteristics of biodegradable polymer scaffolds in their role as DDS for bone regeneration therapy.

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“…These cells have generated considerable excitement for their potential use in regenerative medicine and the treatment of intractable diseases. Studies have also been conducted on the clinical application of iPS cells for seeding on nanofiber scaffolds in bone regeneration [76,77].…”

Section: Cells For Bone Regeneration and Signaling Moleculesmentioning

confidence: 99%

The Use of Electrospun Organic and Carbon Nanofibers in Bone Regeneration

2020

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There has been an increasing amount of research on regenerative medicine for the treatment of bone defects. Scaffolds are needed for the formation of new bone, and various scaffolding materials have been evaluated for bone regeneration. Materials with pores that allow cells to differentiate into osteocytes are preferred in scaffolds for bone regeneration, and porous materials and fibers are well suited for this application. Electrospinning is an effective method for producing a nanosized fiber by applying a high voltage to the needle tip containing a polymer solution. The use of electrospun nanofibers is being studied in the medical field, and its use as a scaffold for bone regeneration therapy has become a topic of growing interest. In this review, we will introduce the potential use of electrospun nanofiber as a scaffold for bone regenerative medicine with a focus on carbon nanofibers produced by the electrospinning method.

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Transplantation of human-induced pluripotent stem cells carried by self-assembling peptide nanofiber hydrogel improves bone regeneration in rat calvarial bone defects

Cited by 37 publications

References 36 publications

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model

Biodegradable Polymers as Drug Delivery Systems for Bone Regeneration

The Use of Electrospun Organic and Carbon Nanofibers in Bone Regeneration

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