Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment

Bou-yue Peng, Chi-Sheng Chiou, Navneet Kumar Dubey, Sung Hsun Yu, Yue Hua Deng, Feng Chou Tsai, Han Sun Chiang, Ying-Hua Shieh, Wei Hong Chen, Win-Ping Deng

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL. Next, their cell morphology, population doubling time (PDT) and colony forming ability (CFU) were evaluated. Furthermore, pluripotency and immunophenotypic markers were investigated. To deduce therapeutic ability, iBMSCs-mCL were intra-articularly injected into right knee of anterior cruciate ligament transaction (ACLT)-OA mice model and tracked through non-invasive bioluminescence imaging. Cell morphology of iBMSCs-mCL was similar to parental BMSCs. PDT and CFU ability of iBMSCs-mCLs were significantly increased. Pluripotency and immunophenotypic markers were highly expressed in iBMSC-mCL. Long-term survival and tri-lineage differentiation particularly chondrogenic potential of iBMSCs-mCL were also demonstrated in vitro and then in vivo which was monitored through non-invasive imaging. Intensive bioluminescent signals in iBMSCs-mCL administered knee-joint indicated a marked in vivo survival and proliferation of iBMSCs-mCL. Immunohistochemical staining for type II collagen (IHC of Col II) and alcian blue & safranin o staining of proteoglycans also corroborated cartilage regeneration by iBMSCs-mCL. Conclusively, iBMSCs-mCL maintains stemness and in vivo cartilage regeneration potential suggesting a promising avenue for development of OA therapeutics.
原文英語
頁(從 - 到)97153-97164
期刊Oncotarget
8
發行號57
出版狀態已發佈 - 九月 27 2017

指紋

Molecular Imaging
Luciferases
Bone Marrow Cells
Osteoarthritis
Stem Cells
Cell Aging
Knee Joint
Papillomaviridae
Cartilage
Regeneration
Staining and Labeling
Population
Chondrogenesis
Alcian Blue
Collagen Type II
Anterior Cruciate Ligament
Articular Cartilage
Proteoglycans
Chondrocytes
Knee

引用此文

Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment. / Peng, Bou-yue; Chiou, Chi-Sheng; Dubey, Navneet Kumar; Yu, Sung Hsun; Deng, Yue Hua; Tsai, Feng Chou; Chiang, Han Sun; Shieh, Ying-Hua; Chen, Wei Hong; Deng, Win-Ping.

於: Oncotarget, 卷 8, 編號 57, 27.09.2017, p. 97153-97164.

研究成果: 雜誌貢獻文章

Peng, Bou-yue ; Chiou, Chi-Sheng ; Dubey, Navneet Kumar ; Yu, Sung Hsun ; Deng, Yue Hua ; Tsai, Feng Chou ; Chiang, Han Sun ; Shieh, Ying-Hua ; Chen, Wei Hong ; Deng, Win-Ping. / Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment. 於: Oncotarget. 2017 ; 卷 8, 編號 57. 頁 97153-97164.
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abstract = "Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL. Next, their cell morphology, population doubling time (PDT) and colony forming ability (CFU) were evaluated. Furthermore, pluripotency and immunophenotypic markers were investigated. To deduce therapeutic ability, iBMSCs-mCL were intra-articularly injected into right knee of anterior cruciate ligament transaction (ACLT)-OA mice model and tracked through non-invasive bioluminescence imaging. Cell morphology of iBMSCs-mCL was similar to parental BMSCs. PDT and CFU ability of iBMSCs-mCLs were significantly increased. Pluripotency and immunophenotypic markers were highly expressed in iBMSC-mCL. Long-term survival and tri-lineage differentiation particularly chondrogenic potential of iBMSCs-mCL were also demonstrated in vitro and then in vivo which was monitored through non-invasive imaging. Intensive bioluminescent signals in iBMSCs-mCL administered knee-joint indicated a marked in vivo survival and proliferation of iBMSCs-mCL. Immunohistochemical staining for type II collagen (IHC of Col II) and alcian blue & safranin o staining of proteoglycans also corroborated cartilage regeneration by iBMSCs-mCL. Conclusively, iBMSCs-mCL maintains stemness and in vivo cartilage regeneration potential suggesting a promising avenue for development of OA therapeutics.",
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AU - Deng, Yue Hua

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