title: Cell Therapy With G-CSF-Mobilized Stem Cells in a Rat Osteoarthritis Model.
abstract: G-CSF-mobilized peripheral blood stem cells (gm-PBSCs) offer a convenient cell source for treatment of hematopoietic and vascular disorders. Whether gm-PBSCs provide beneficial effects on skeleton diseases, such as osteoarthritis (OA), remains unknown. This study was undertaken to address the hypothesis that gm-PBSCs promote articular regeneration in OA. Here we studied the effect of single-dose intra-articular injection of gm-PBSCs from male donors delivered in hyaluronic acid (HA) on papain-induced OA in the knee joints of female Sprague-Dawley (SD) rats. Contralateral OA knee joints received single-dose HA alone and served as vehicle controls. We evaluated the histologic changes in glycosaminoglycan, type II collagen, type X collagen, modified Mankin score, and cell apoptosis rate in the articular cartilage of rat knees. We demonstrated that gm-PBSCs were mobilized to the peripheral blood via G-CSF infusion for 5 days in SD rats with increasing CD34(+) percentage up to 55-fold. We showed that gm-PBSCs inhibit progression of papain-induced OA via reducing articular surface irregularity, fibrillation, and erosion, preventing cellular necrosis and loss of chondrogenic proteins, such as glycosaminoglycan and type II collagen, at both 3 and 6 weeks after treatment. Moreover, gm-PBSCs reduced modified Mankin scores and cellular apoptosis rates compared with HA alone. Our findings demonstrate that HA plus gm-PBSCs, rather than HA alone, inhibits progression of OA in rats in vivo. Thus, intra-articular injection of gm-PBSCs is a convenient protocol for treating OA with consistent beneficial effects.
authors.affiliation: Enhance Biomedical Ltd., Taipei, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Deng
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Wei
authors.forename: Tu-Lai
authors.initials: TL
authors.lastname: Yew
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Lee
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Yang
authors.forename: Hen-Yi
authors.initials: HY
authors.lastname: Chu
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D024043:Collagen Type II / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007270:Injections, Intra-Articular; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
chemical_list: D018952:Antigens, CD34; D024043:Collagen Type II; D024121:Collagen Type X; D006025:Glycosaminoglycans; D016179:Granulocyte Colony-Stimulating Factor