Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head

The early treatment of Osteonecrosis of Femoral Head (ONFH) remains a clinical challenge. Conventional Bone Marrow Mesenchymal Stem Cell (BMSC) injection methods often result in unsatisfactory outcomes due to mechanical cell damage, low cell survival and retention rates, inadequate cell matrix accum...

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Main Authors: Minzheng Guo, Baochuang Qi, Zijie Pei, Haonan Ni, Junxiao Ren, Huan Luo, Hongxin Shi, Chen Meng, Yang Yu, Zhifang Tang, Yongqing Xu, Qingyun Xue, Chuan Li
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424004873
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author Minzheng Guo
Baochuang Qi
Zijie Pei
Haonan Ni
Junxiao Ren
Huan Luo
Hongxin Shi
Chen Meng
Yang Yu
Zhifang Tang
Yongqing Xu
Qingyun Xue
Chuan Li
author_facet Minzheng Guo
Baochuang Qi
Zijie Pei
Haonan Ni
Junxiao Ren
Huan Luo
Hongxin Shi
Chen Meng
Yang Yu
Zhifang Tang
Yongqing Xu
Qingyun Xue
Chuan Li
author_sort Minzheng Guo
collection DOAJ
description The early treatment of Osteonecrosis of Femoral Head (ONFH) remains a clinical challenge. Conventional Bone Marrow Mesenchymal Stem Cell (BMSC) injection methods often result in unsatisfactory outcomes due to mechanical cell damage, low cell survival and retention rates, inadequate cell matrix accumulation, and poor intercellular interaction. In this study, we employed a novel cell carrier material termed ''3D Microscaffold'' to deliver BMSCs, addressing these issues and enhancing the therapeutic effects of cell therapy for ONFH. We injected 3D microscaffold loaded with low-dose BMSCs or free high-dose BMSCs into the femoral heads of ONFH rats and assessed therapeutic effects using imaging, serology, histology, and immunohistochemistry. To understand the mechanism of efficacy, we established a co-culture model of human osteoblasts and BMSCs, followed by cell proliferation and activity detection, flow cytometry analysis, Quantitative RT-PCR, and Western blotting. Additionally, RNA sequencing was performed on femoral head tissues. Results showed that the 3D microscaffold with low-dose BMSCs had a therapeutic effect comparable to high-dose free BMSCs. Osteoblasts in the 3D microscaffold group exhibited superior phenotypes compared to the non-3D microscaffold group. Furthermore, we have, for the first time, preliminarily validated that the low-dose BMSCs-loaded 3D microscaffolds may promote the repair of femoral head necrosis through the synergistic action of the MAPK and Hippo signaling pathways.
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spelling doaj-art-ba01523e94f045c4890cfa05a45a5c462025-01-17T04:52:11ZengElsevierMaterials Today Bio2590-00642025-02-0130101426Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral headMinzheng Guo0Baochuang Qi1Zijie Pei2Haonan Ni3Junxiao Ren4Huan Luo5Hongxin Shi6Chen Meng7Yang Yu8Zhifang Tang9Yongqing Xu10Qingyun Xue11Chuan Li12Chinese Academy of Medical Sciences & Peking Union Medical College, PR China; Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaChinese Academy of Medical Sciences & Peking Union Medical College, PR China; Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaChinese Academy of Medical Sciences & Peking Union Medical College, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR ChinaDepartment of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR China; Corresponding author.Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China; Corresponding author.Kunming Institute of Zoology, Chinese Academy of Sciences, PR China; Department of Orthopedics, 920th Hospital of Joint Logistics Support Force, PR China; Corresponding author. Kunming Institute of Zoology, Chinese Academy of Sciences, PR China.The early treatment of Osteonecrosis of Femoral Head (ONFH) remains a clinical challenge. Conventional Bone Marrow Mesenchymal Stem Cell (BMSC) injection methods often result in unsatisfactory outcomes due to mechanical cell damage, low cell survival and retention rates, inadequate cell matrix accumulation, and poor intercellular interaction. In this study, we employed a novel cell carrier material termed ''3D Microscaffold'' to deliver BMSCs, addressing these issues and enhancing the therapeutic effects of cell therapy for ONFH. We injected 3D microscaffold loaded with low-dose BMSCs or free high-dose BMSCs into the femoral heads of ONFH rats and assessed therapeutic effects using imaging, serology, histology, and immunohistochemistry. To understand the mechanism of efficacy, we established a co-culture model of human osteoblasts and BMSCs, followed by cell proliferation and activity detection, flow cytometry analysis, Quantitative RT-PCR, and Western blotting. Additionally, RNA sequencing was performed on femoral head tissues. Results showed that the 3D microscaffold with low-dose BMSCs had a therapeutic effect comparable to high-dose free BMSCs. Osteoblasts in the 3D microscaffold group exhibited superior phenotypes compared to the non-3D microscaffold group. Furthermore, we have, for the first time, preliminarily validated that the low-dose BMSCs-loaded 3D microscaffolds may promote the repair of femoral head necrosis through the synergistic action of the MAPK and Hippo signaling pathways.http://www.sciencedirect.com/science/article/pii/S2590006424004873Osteonecrosis of the femoral headStem cellMicroscaffold
spellingShingle Minzheng Guo
Baochuang Qi
Zijie Pei
Haonan Ni
Junxiao Ren
Huan Luo
Hongxin Shi
Chen Meng
Yang Yu
Zhifang Tang
Yongqing Xu
Qingyun Xue
Chuan Li
Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head
Materials Today Bio
Osteonecrosis of the femoral head
Stem cell
Microscaffold
title Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head
title_full Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head
title_fullStr Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head
title_full_unstemmed Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head
title_short Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head
title_sort therapeutic effect of low dose bmscs loaded 3d microscaffold on early osteonecrosis of the femoral head
topic Osteonecrosis of the femoral head
Stem cell
Microscaffold
url http://www.sciencedirect.com/science/article/pii/S2590006424004873
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