Mesenchymal stromal cells genetically engineered to overexpress IGF-I enhance cell-based gene therapy of renal failure-induced anemia

Kucic, Terrence; Copland, Ian B.; Cuerquis, Jessica; Coutu, Daniel L.; Chalifour, Lorraine E.; Gagnon, Raymonde F.; Galipeau, Jacques

doi:10.1152/ajprenal.00044.2008

Cited by 31 publications

(18 citation statements)

References 47 publications

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“…65,66 They next demonstrated that co-transplantation of insulin-like growth factor I (IGF-I)-overexpressing MSC improved the MSC-based gene therapy of anemia by providing paracrine support to Epo-secreting MSC. 67 Mice were rendered anemic by right kidney electrocoagulation and left nephrectomy. MSC engineered to express Epo were subsequently implanted subcutaneously in a bovine collagen matrix, in combination with MSC expressing IGF-1 or MSC alone in mice with renal failure.…”

Section: Systemic Cytokine Production From Genetically Engineered mentioning

confidence: 99%

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Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors

Meyerrose

Olson

Pontow

et al. 2010

Advanced Drug Delivery Reviews

157

117

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Section: Systemic Cytokine Production From Genetically Engineered mentioning

confidence: 99%

“…Their strategy of coimplantation of MSC-IGF with MSC-Epo therefore represents a promising strategy for improving cell-based gene therapy of renal anemia. 67 …”

Section: Systemic Cytokine Production From Genetically Engineered mentioning

confidence: 99%

Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors

Meyerrose

Olson

Pontow

et al. 2010

Advanced Drug Delivery Reviews

157

117

View full text Add to dashboard Cite

“…Their data showed that these cells led to an increase in hematocrit when admixed in a bovine collagen matrix and implanted by subcutaneous injection in mice. More recently, the same group has demonstrated that delivery of MSCs overexpressing a combination of EPO and IGF-1 resulted in enhanced hematocrit elevation, as well as improved cardiac function, compared with animals receiving MSCs expressing EPO alone (Kucic et al, 2008).…”

Section: Renal Failurementioning

confidence: 99%

Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

et al. 2010

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The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

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“…To investigate the therapeutic effect of GMME1, DBA/1 mice with pre-established bovine collagen-induced inflammatory arthritis were used as a surrogate model of human RA. Arthritic mice were implanted with a neoorganoid implant composed of CCL2 Ϫ/Ϫ mesenchymal stromal cells (MSCs) gene-engineered to continually express and deliver GMME1 to the host, akin to what we have previously described (14,15,16,17,18). We analyzed the impact on clinical disease score as well as levels of systemic and articular inflammatory cytokines and documented clinical remission coupled to a robust reduction of pathogenic cytokines.…”

Section: R Heumatoid Arthritis (Ra)mentioning

confidence: 99%

An Engineered GM-CSF-CCL2 Fusokine Is a Potent Inhibitor of CCR2-Driven Inflammation As Demonstrated in a Murine Model of Inflammatory Arthritis

Rafei

Berchiche²,

Birman³

et al. 2009

The Journal of Immunology

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CCR2 is a chemokine receptor widely expressed by lymphomyeloid cells involved in maladaptive autoimmune ailments. Therefore CCR2 is of great interest as a biological target for immune suppression due to its direct implication in autoimmune diseases such as rheumatoid arthritis. We have generated a novel fusion protein using GM-CSF and an N-terminal truncated version of MCP-1/CCL2 (6–76, GMME1) and investigated its utility as a CCR2-specific immune suppressor. Using BRET studies, we found that distinct to CCL2, GMME1 binding to CCR2 led to altered conformational changes in the CCR2 homodimer and did not induce the recruitment of β-arrestin 2 to the receptor. However, CCR2-dependent calcium mobilization, BAX induction and caspase-3 activation followed by cell death was observed. Using Th17 cells harvested from DBA/1 mice ill with bovine collagen-induced arthritis, we demonstrate that GMME1 is capable of blocking their production of IL-17 in vitro. Upon its delivery to mice symptomatic with inflammatory arthritis, a robust clinical recovery occurred with decreased paw thickness to normal levels and a significant reduction in anti-collagen Ab titer and rheumatoid factor titer, as well as reduction of proinflammatory cytokines levels both intraarticular and systemic. Our data demonstrate that GMME1 is a powerful synthetic suppressor cytokine that coopts CCR2-dependent cellular signaling and blunts the effects of CCR2-expressing lymphomyeloid cells causative of autoimmune arthritis.

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Mesenchymal stromal cells genetically engineered to overexpress IGF-I enhance cell-based gene therapy of renal failure-induced anemia

Abstract: Kucic T, Copland IB, Cuerquis J, Coutu DL, Chalifour LE, Gagnon RF, Galipeau J. Mesenchymal stromal cells genetically engineered to overexpress IGF-I enhance cell-based gene therapy of renal failure-induced anemia.

Cited by 31 publications

References 47 publications

Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors

Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors

Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

An Engineered GM-CSF-CCL2 Fusokine Is a Potent Inhibitor of CCR2-Driven Inflammation As Demonstrated in a Murine Model of Inflammatory Arthritis

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