Characterization and biodistribution of human mesenchymal stem cells transduced with lentiviral-mediated BMP2

Choi, Kyoung Hwa; Ahn, Soon Young; Kim, Tek Seung; Kim, Jiseon; Kim, Byoung-Guk; Han, Kyung Ho; Ban, Sang Ja; Kim, Hyung Soo; Choi, Yong; Lim, Chul-Joo

doi:10.1007/s12272-011-0410-y

Cited by 11 publications

(6 citation statements)

References 21 publications

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“…In the present study, the odontogenic differentiation mRNA expression, including ALP, OCN, DSPP and DMP1, was also significantly upregulated in SCAP/BMP2 compared with SCAP/Vector. Although in this study, BMP2 expression was only tested on the 4th day following gene transfection in, other studies have proven that lentivirus transfection can mediate a stable expression of target genes in cells (23–25). …”

Section: Discussionmentioning

confidence: 99%

Proliferation and odontogenic differentiation of BMP2 gene-transfected stem cells from human tooth apical papilla: An in vitro study

Wen

Zhang

Ling

et al. 2014

International Journal of Molecular Medicine

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Stem cells from the apical papilla (SCAP) have odontogenic potential, which plays a pivotal role in the root dentin development of permanent teeth. Human bone morphogenetic protein 2 (BMP2) is a well-known gene that participates in regulating the odontogenic differentiation of dental tissue-derived stem cells. However, little is known regarding the effects of the BMP2 gene on the proliferation and odontogenic differentiation of SCAP. This study aimed to evaluate the odontogenic differentiation potential of lentiviral-mediated BMP2 gene-transfected human SCAP (SCAP/BMP2) in vitro. SCAP were isolated by enzymatic dissociation of human teeth apical papillae. The multipotential of SCAP was verified by their osteogenic and adipogenic differentiation characteristics. The phenotype of SCAP was evaluated by flow cytometry (FCM). The proliferation status of the blank vector-transfected SCAP (SCAP/Vector) and SCAP/BMP2 was analyzed by a cell counting kit-8 (CCK-8). Odontogenic genes, including alkaline phosphatase (ALP), osteocalcin (OCN), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) of the two groups of cells were evaluated by quantitative polymerase chain reaction (qPCR). ALP staining and alizarin red (AR) staining of the cells was performed on the 16th day after transfection. In vitro results of CCK-8, qPCR, ALP and AR staining demonstrated that: i) SCAP/BMP2 had a comparable proliferation rate to SCAP/Vector; ii) SCAP/BMP2 presented significantly better potential to differentiate into odontoblasts compared to SCAP/Vector by upregulating ALP, OCN, DSPP and DMP1 genes; iii) more ALP granules and mineralized deposits were formed by SCAP/BMP2 as compared to SCAP/Vector. The results suggested that lentiviral-mediated BMP2 gene transfection enhances the odontogenic differentiation capacity of human SCAP in vitro.

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Section: Discussionmentioning

confidence: 99%

Proliferation and odontogenic differentiation of BMP2 gene-transfected stem cells from human tooth apical papilla: An in vitro study

Wen

Zhang

Ling

et al. 2014

International Journal of Molecular Medicine

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“…(30)(31)(32) However, our previous study and one other have evaluated the biodistribution and safety of gene therapy to heal bone defects. (33,34) Choi et al evaluated the biodistribution 28 days post-implantation of 3 study groups: mesenchymal stem cells (MSCs), lentiviral-mediated GFP transduced MSCs (MSCs-GFP), and lentiviral-mediated BMP-2 transduced MSCs (MSCs-BMP-2). Nontransduced and transduced cells were injected into the tail vein of mice with fractured femurs and cells were detected in the liver, spleen, and testis at 2 weeks following administration and found no signs of tumor formation.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution of lentiviral transduced adipose-derived stem cells for “ex-vivo” regional gene therapy for bone repair

et al. 2023

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Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in preclinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety pro le becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein 2 (LV-TSTA-BMP-2). Animals were sacri ced at 4-, 14-, 56-, and 84-days post implantation. Treatment groups included 1) standard dose LV-TSTA-BMP-2 2) high dose LV-TSTA-BMP-2, 3) standard dose LV-TSTA-GFP 4) high dose LV-TSTA-GFP and 5) standard dose nontransduced cells. The viral load was assessed at each timepoint in the defect in ten organs and the defect site. Histology of all organs, ipsilateral tibia, and femur were evaluated at each timepoint. There were nearly undetectable levels of LV-TSTA-BMP-2 transduced cells at the defect site at 84 days and no pathologic changes in any organ at all timepoints. Humana ASCs transduced with LV-TSTA may be a safe and effective treatment option when adopted for us in patients.

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“…Additionally, osteogenesis of M-cMSCs appeared to be higher than that of F-cMSCs based on protein levels and transcripts of osteogenic markers ALP, BSP, and OCN. 34 …”

Section: Discussionmentioning

confidence: 99%

The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation

Bugueño

Salat

et al. 2017

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Objectives Mesenchymal stem cells (MSCs) are promising therapies in dentistry due to their multipotent properties. Selecting donor MSCs is crucial because beagle dogs (canines) commonly used in pre-clinical studies have shown variable outcomes and it is unclear whether canine MSCs (cMSCs) are skeletal site-specific. This study tested whether jaw and long bone cMSCs have disparate in vitro and in vivo multilineage differentiation capabilities. Study Design Primary cMSCs were isolated from mandible (M-cMSCs) and femur (F-cMSCs) of four healthy Beagle dogs. Femur served as non-oral control. Clonogenic and proliferative abilities were assessed. In vitro osteogenic, chondrogenic, adipogenic and neural multilineage differentiation were correlated with in vivo bone regeneration and potential for clinical applications. Results M-cMSCs displayed two-fold increase in clonogenic and proliferative capacities relative to F-cMSCs (p =0.006). M-cMSCs in vitro osteogenesis based on alkaline phosphatase (p =0.04), bone sialoprotein (p =0.05), and osteocalcin (p =0.03), as well as adipogenesis (p =0.007), and chondrogenesis (p =0.009) were relatively higher and correlated with enhanced M-cMSC bone regenerative capacity. Neural expression markers, nestin and βIII-tubulin were not significantly different. Conclusions The enhanced differentiation and bone regenerative capacity of mandible MSCs may make them favorable donor graft materials for site-specific jaw bone regeneration.

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Characterization and biodistribution of human mesenchymal stem cells transduced with lentiviral-mediated BMP2

Cited by 11 publications

References 21 publications

Proliferation and odontogenic differentiation of BMP2 gene-transfected stem cells from human tooth apical papilla: An in vitro study

Proliferation and odontogenic differentiation of BMP2 gene-transfected stem cells from human tooth apical papilla: An in vitro study

Biodistribution of lentiviral transduced adipose-derived stem cells for “ex-vivo” regional gene therapy for bone repair

The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation

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