Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration

Background. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic...

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Main Authors: Kaishun Xia, Jian Zhu, Jianming Hua, Zhe Gong, Chao Yu, Xiaopeng Zhou, Jingkai Wang, Xianpeng Huang, Wei Yu, Liming Li, Jianqing Gao, Qixin Chen, Fangcai Li, Chengzhen Liang
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/6806540
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author Kaishun Xia
Jian Zhu
Jianming Hua
Zhe Gong
Chao Yu
Xiaopeng Zhou
Jingkai Wang
Xianpeng Huang
Wei Yu
Liming Li
Jianqing Gao
Qixin Chen
Fangcai Li
Chengzhen Liang
author_facet Kaishun Xia
Jian Zhu
Jianming Hua
Zhe Gong
Chao Yu
Xiaopeng Zhou
Jingkai Wang
Xianpeng Huang
Wei Yu
Liming Li
Jianqing Gao
Qixin Chen
Fangcai Li
Chengzhen Liang
author_sort Kaishun Xia
collection DOAJ
description Background. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs. Methods. A polymeric gelatin microsphere (GM) was generated for sustained release of growth and differentiation factor-5 (GDF-5) and as a cell delivery vehicle of NP-lCs. By injecting NP-lC-seeded GDF-5-loaded GMs into the rat coccygeal intervertebral discs, the disc height and water content were examined with the molybdenum target radiographic imaging test and magnetic resonance imaging examination. Histology and immunohistochemistry results were shown with H&E, S-O-Fast Green, and immunohistochemistry staining. Results. We demonstrated that the injection of NP-lC-seeded GDF-5-loaded GMs could reverse IDD in a rat model. The imaging examination indicated that disc height recovered and water content increased. Histology and immunohistochemistry results indicated that the NP cells as well as their extracellular matrix were partially restored. Conclusions. The results suggest that NP-lC-seeded GDF-5-loaded GMs could partially regenerate degenerated intervertebral discs after transplantation into rat coccygeal intervertebral discs. Our study will help develop a promising method of stem cell-based therapy for IDD.
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spelling doaj-art-c8bbfb47344f432890d6649a541ed76a2025-02-03T05:53:03ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/68065406806540Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc RegenerationKaishun Xia0Jian Zhu1Jianming Hua2Zhe Gong3Chao Yu4Xiaopeng Zhou5Jingkai Wang6Xianpeng Huang7Wei Yu8Liming Li9Jianqing Gao10Qixin Chen11Fangcai Li12Chengzhen Liang13Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaInstitute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 Zhejiang, ChinaInstitute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaDepartment of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, ChinaBackground. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs. Methods. A polymeric gelatin microsphere (GM) was generated for sustained release of growth and differentiation factor-5 (GDF-5) and as a cell delivery vehicle of NP-lCs. By injecting NP-lC-seeded GDF-5-loaded GMs into the rat coccygeal intervertebral discs, the disc height and water content were examined with the molybdenum target radiographic imaging test and magnetic resonance imaging examination. Histology and immunohistochemistry results were shown with H&E, S-O-Fast Green, and immunohistochemistry staining. Results. We demonstrated that the injection of NP-lC-seeded GDF-5-loaded GMs could reverse IDD in a rat model. The imaging examination indicated that disc height recovered and water content increased. Histology and immunohistochemistry results indicated that the NP cells as well as their extracellular matrix were partially restored. Conclusions. The results suggest that NP-lC-seeded GDF-5-loaded GMs could partially regenerate degenerated intervertebral discs after transplantation into rat coccygeal intervertebral discs. Our study will help develop a promising method of stem cell-based therapy for IDD.http://dx.doi.org/10.1155/2019/6806540
spellingShingle Kaishun Xia
Jian Zhu
Jianming Hua
Zhe Gong
Chao Yu
Xiaopeng Zhou
Jingkai Wang
Xianpeng Huang
Wei Yu
Liming Li
Jianqing Gao
Qixin Chen
Fangcai Li
Chengzhen Liang
Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration
Stem Cells International
title Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration
title_full Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration
title_fullStr Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration
title_full_unstemmed Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration
title_short Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration
title_sort intradiscal injection of induced pluripotent stem cell derived nucleus pulposus like cell seeded polymeric microspheres promotes rat disc regeneration
url http://dx.doi.org/10.1155/2019/6806540
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