Retrovirus‐Mediated Gene Transfer of Receptor Activator of Nuclear Factor‐κB‐Fc Prevents Bone Loss in Ovariectomized Mice

Kim, Do-Hee; Cho, Sun Wook; Her, Sun Ju; Yang, Jae Yun; Kim, Sang Wan; Kim, Seong Yeon; Shin, Chan Soo

doi:10.1634/stemcells.2005-0480

Cited by 30 publications

(22 citation statements)

References 40 publications

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“…145 Overexpression of RANK-Fc in mMSCs was found to increase bone mineral density in ovariectomized mice. 146 Moreover, Horwitz et al 147 showed that children with Osteogenesis Imperfecta, a genetic disease characterized by production of defective type I collagen, improved their bone histology and clinical outcome after un-manipulated administration of bone marrow cells. Thereafter, the same group showed that when BM-MSCs were administered into children with Osteogenesis Imperfecta, their clinical outcome was improved.…”

Section: Mscs As Vehicles Of Therapeutic Genes In Non-cancerous Diseasementioning

confidence: 99%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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Mesenchymal stem (stromal) cells (MSCs) are a source of circulating progenitors that are able to generate cells of all mesenchymal lineages and to cover cellular demands of injured tissues. The extent of their transdifferentiation plasticity remains controversial. Cells with MSC properties have been obtained from diverse tissues after purification and expansion in vitro. These cellular populations are heterogeneous and under certain conditions show pluripotent-like properties. MSCs present immunosuppressive and anti-inflammatory features and high migratory capacity toward inflamed or remodeling tissues. In this study we review available data regarding factors and signaling axes involved in the chemoattraction and engraftment of MSCs to an injured tissue or to a tissue undergoing active remodeling. Moreover, experimental evidence in support of uses of MSCs as vehicles of therapeutic genes is discussed. Because of its regenerative capacity and its particular immune properties, the liver is a good model to analyze the potential of MSCbased therapies. Finally, the potential application of MSCs and genetically modified MSCs in liver fibrosis and hepatocellular carcinoma (HCC) is proposed in view of available evidence.

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Section: Mscs As Vehicles Of Therapeutic Genes In Non-cancerous Diseasementioning

confidence: 99%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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“…Tissue-specific homing and engraftment of MSCs could be achieved by the introduction of genes for tissue-specific cell surface adhesion molecules. Furthermore, as MSCs engraft in damaged tissues, genetically engineered MSCs could be employed as a means of delivering therapeutically active proteins to these tissues (Stagg et al, 2004;Reiser et al, 2005;Kim et al, 2006;Goncalvos et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Adeno-associated viral vector transduction of human mesenchymal stem cells

Stender

Murphy²,

O’Brien³

et al. 2007

eCM

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Mesenchymal stem cells (MSCs) have received considerable attention in the emerging field of regenerative medicine. One aspect of MSC research focuses on genetically modifying the cells with the aim of enhancing their regenerative potential. Adeno-associated virus (AAV) holds promise as a vector for human gene therapy, primarily due to its lack of pathogenicity and low risk of insertional mutagenesis. However, the existing data pertaining to AAV transduction of MSCs is limited.The objective of this work was to examine the efficiency and kinetics of in vitro transduction using AAV serotype 2 in human MSCs and to assess whether AAV transduction affects MSC multipotentiality. The results indicated that human MSCs could indeed be transiently transduced in vitro by the AAV2 vector with efficiencies of up to 65%. The percentage of GFP-positive cells peaked at 4 days posttransduction and declined rapidly towards 0% after day 8. The level of transgene expression in the GFP-positive population increased 4-fold over a 10,000 fold viral dose increase. This dose-response contrasted with the 200-fold increase observed in similarly transduced 293-cells, indicating a relatively restricted transgene expression in MSCs following AAV mediated gene delivery. Importantly, transduced MSCs retained multipotential activity comparable to untransduced controls.

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“…Indeed, our previous study that evaluated the effects of syngeneic transplantation of BMMSCs with retroviral transduction of RANK-Fc, a soluble inhibitor of osteoclast differentiation, demonstrated poor homing of transplanted cells to bone tissue in vivo. 16 Furthermore, cotransduction of CXCR4, a chemokine that enhances homing to BM spaces across the stromal cell-derived factor-1 gradient, did not improve engrafting of the transplanted BM-MSCs in the long term, although the bone mass gain was greater compared with that achieved by CXCR4 ( -) cells. 17 Consistent with these studies, the efficiencies of shortterm homing and long-term engraftment of hUCB-MSCs in this study do not seem to be sufficient for any positive effects on bone mass.…”

Section: Discussionmentioning

confidence: 94%

“…Whole-body BMD and bone mineral content were measured at 4 weeks prior (before OVX or Sham-op) and 0 (before treatment), 4, and 8 weeks after treatment using a PIXImus II densitometer (software version 2.0; GE Lunar, Madison, WI) as described. 16 Microcomputed tomography analysis. After 8 weeks of treatment, all mice were sacrificed, and right tibiae from each mouse were isolated and fixed in 70% ethanol for microcomputed tomography (microCT).…”

Section: Effects Of Hucb-mscs and CM On Ovx Nude Micementioning

confidence: 99%

“…We previously reported the protective effect of systemic transplantation of syngeneic murine bone marrow-derived MSCs (BM-MSCs) that were retrovirally transduced with RANK-Fc 16 or RANK-Fc + CXCR4 17 in ovariectomy (OVX)-induced bone loss in mice. In these studies, transplantation of MSCs effectively prevents bone loss despite their poor BM homing and short-term engraftment, suggesting that these favorable effects are mediated by secretory factors from MSCs rather than direct engraftment.…”

Section: Introductionmentioning

confidence: 99%

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Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

Park

Song

et al. 2013

Tissue Engineering Part A

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Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCBMSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

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Retrovirus‐Mediated Gene Transfer of Receptor Activator of Nuclear Factor‐κB‐Fc Prevents Bone Loss in Ovariectomized Mice

Cited by 30 publications

References 40 publications

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Adeno-associated viral vector transduction of human mesenchymal stem cells

Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

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