Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment
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Bou-Yue Peng1,2, Chi-Sheng Chiou2,3, Navneet Kumar Dubey4,5, Sung-Hsun Yu4,6, Yue-Hua Deng4,7, Feng-Chou Tsai8, Han-Sun Chiang7, Ying-Hua Shieh10,11, Wei-Hong Chen4 and Win-Ping Deng2,4,9
1Oral and Maxillofacial Surgery Section, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan
2School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
3Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
4Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
5Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
6Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
7Department of Life Science, Fu Jen Catholic University, Taipei, Taiwan
8Department of Stem Cell Research, Cosmetic Clinic Group, Taipei, Taiwan
9Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan
10Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
11Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
Win-Ping Deng, email: [email protected]
Keywords: osteoarthritis (OA), immortalized bone marrow stem cells (iBMSCs), cartilage regeneration, human papilloma virus (HPV)-16 E6/E7, molecular imaging
Received: July 14, 2017 Accepted: August 27, 2017 Published: September 27, 2017
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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