Bone marrow stromal cells as a vehicle for gene transfer

Ding, Lie; Lu, Song Qing; Batchu, Ramesh B.; Saylors, Robert L.; Munshi, Nikhil C.

doi:10.1038/sj.gt.3300973

Cited by 66 publications

(40 citation statements)

References 27 publications

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“…The proteins included the Escherichia coli β-galactosidase [15,40], GFP [14,18,19] and red fluorescent protein (DsRed) [19], as well as many therapeutic proteins, including coagulation factors VIII [12,16,17] and IX [41][42][43], IL-3 [15,44,45] and IL-7 [46], human growth hormone [41], human erythropoietin (hEPO) [47] and murine erythropoietin (mEPO) [48], arylsulfatase A [49,50], tyrosine hydroxylase GTP cyclohydrolase I [13,51], α-L-iduronidase [52], β-hexosaminidase A [53] and bone morphogenetic protein (BMP) [54]. It remains to be determined how MSCs perform relative to other mammalian expression systems, such as Chinese hamster ovary cells, in terms of transgene expression levels.…”

Section: Mesenchymal Stem Cells As Platforms For Recombinant Protein mentioning

confidence: 99%

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

Reiser

Zhang

Hemenway

et al. 2005

Expert Opinion on Biological Therapy

166

114

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The intriguing biology of stem cells and their vast clinical potential is emerging rapidly for gene therapy. Bone marrow stem cells, including the pluripotent haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and possibly the multipotent adherent progenitor cells (MAPCs), are being considered as potential targets for cell and gene therapy-based approaches against a variety of different diseases. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineagesn and, at least in vitro, have significant expansion capability. The apparently high self-renewal potential makes them strong candidates for delivering genes and restoring organ systems function. However, the high proliferative potential of MSCs, now presumed to be self-renewal, may be more apparent than real. Although expanded MSCs have great proliferation and differentiation potential in vitro, there are limitations with the biology of these cells in vivo. So far, expanded MSCs have failed to induce durable therapeutic effects expected from a true self-renewing stem cell population. The loss of in vivo self-renewal may be due to the extensive expansion of MSCs in existing in vitro expansion systems, suggesting that the original stem cell population and/or properties may no longer exist. Rather, the expanded population may indeed be heterogeneous and represents several generations of different types of mesenchymal cell progeny that have retained a limited proliferation potential and responsiveness for terminal differentiation and maturation along mesenchymal and non-mesenchymal lineages. Novel technology that allows MSCs to maintain their stem cell function in vivo is critical for distinguishing the elusive stem cell from its progenitor cell populations. The ultimate dream is to use MSCs in various forms of cellular therapies, as well as genetic tools that can be used to better understand the mechanisms leading to repair and regeneration of damaged or diseased tissues and organs.

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Section: Mesenchymal Stem Cells As Platforms For Recombinant Protein mentioning

confidence: 99%

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

Reiser

Zhang

Hemenway

et al. 2005

Expert Opinion on Biological Therapy

166

114

View full text Add to dashboard Cite

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“…Genetic modifications of primary hepatocytes row stromal stem cells have been found to be readily cultured in vitro and expanded for prolonged periods have been performed by numerous investigators using a variety of different vector systems. One of the main (6,29). An additional factor that would benefit ex vivo gene manipulation in transplantable cells would be to problems is that these cells are difficult to transduce in culture and propagation of these cells cannot be maindesign vector systems that would maximize long-term, therapeutic expression of a transgene of interest.…”

Section: Introductionmentioning

confidence: 99%

“…To circumvent these issues, bone marrow-derived cells, which is a current area of intense research, may be used as an alternate source (6,29). Bone marrow stem The development of cell-based therapies to treat organ failures, such as the liver, has been studied as an cells can be divided into two main groups: hematopoietic and stromal cell lineages.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of Murine Bone Marrow Stromal Cells under the Kidney Capsule to Secrete Coagulation Factor VIII

Peister

Ohashi

et al. 2006

Cell Transplant

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Ectopic cell transplantation has been studied as an alternative to whole organ transplantation or as a method to produce secretable proteins for genetic disorders. In this study, bone marrow stromal cells isolated from C57Bl/6 mice were genetically modified to express either lacZ-or B-domain-deleted human factor VIII. In vitro modification of the isolated bone marrow stromal cells was initially performed by transducing increased doses of VSV-G pseudotyped lentiviral vectors expressing lacZ. At a MOI of 25, all of the bone marrow stromal cells were X-gal positive, which maintained their ability to expand and differentiate prior to transplantation into mice. Extremely poor engraftment was observed in the liver, but transplantation of the bone marrow stromal cells expressing lacZ under the kidney capsule resulted in long-term viable X-gal-positive cells for at least 8 weeks (length of study). In vitro expression of human factor VIII was detected in a dose-dependent manner following bone marrow stromal cell with a factor VIII-expressing lentiviral vector. Transplantation of the factor VIII-expressing bone marrow stromal cells under the kidney capsule led to long-term therapeutic expression in the mouse plasma (1-3 ng/ml; n = 4-5 mice/group) for 8 weeks. This study demonstrated that ectopic transplantation of bone marrow stromal cells under the kidney capsule can be effective as a method to express secretable proteins in vivo.

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“…No report has extended beyond 4 months post-transplantation of transduced cells [3,31]. In most instances, expression decreases with time [32] due to promoter inactivation [33] and/or loss of transduced cells. Although these results are promising, they highlight the need for careful consideration of ex vivo methods, choice of promoter to direct the desired biological activity, and assessment of the self-maintenance of transduced MSCs upon in vivo transplantation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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Postmenopausal osteoporosis is characterized by increased bone resorption due to estrogen deficiency. Receptor activator of nuclear factor-B-Fc (RANK-Fc), a fusion protein that specifically blocks receptor activator of nuclear factor ligand binding to RANK, has been known to be efficient and well tolerated in animal models of osteoporosis. RANK-Fc; n ‫؍‬ 8). Cellular expression of RANK-Fc was confirmed byWestern blot analysis of cell lysates and conditioned medium and also by enzyme-linked immunosorbent assay for the mice serum. Measurement of bone mineral density (BMD) by dual-energy x-ray absorptiometry (PIXImus) revealed that the OVX-RANK-Fc group gained significantly higher BMD than either the OVX-PBS group or OVX-GFP group after 8 weeks. The expression of GFP, which is coexpressed with RANK-Fc, was detected by polymerase chain reaction analysis of DNA isolated from femur and intra-abdominal fat, whereas no GFP signal was identified in liver, brain, heart, lung, or bone marrow aspirates. These suggest that expression of RANK-Fc by genetically modified MSCs may be a feasible option for the prevention of bone loss induced by ovariectomy.

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Bone marrow stromal cells as a vehicle for gene transfer

Cited by 66 publications

References 27 publications

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases

Transplantation of Murine Bone Marrow Stromal Cells under the Kidney Capsule to Secrete Coagulation Factor VIII

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

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