Enhanced engraftment of EPO-transduced human bone marrow stromal cells transplanted in a 3D matrix in non-conditioned NOD/SCID mice

Daga, Antonio; Muraglia, Anita; Quarto, Rodolfo; Cancedda, Ranieri; Corte, Giorgio

doi:10.1038/sj.gt.3301727

Cited by 45 publications

(36 citation statements)

References 20 publications

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“…130,131 The use of MSCs as a vector to deliver EPO 132 through intravenous injection for ocular disorders is feasible in the future as these cells could home into the inflammatory site 133,134 and cross the BRB. 7,31,[33][34][35] The presence of EPO in stem cells could also enhance the survivability of transplanted cells 128,135 in local (intraocular) site of injection. Guan et al 76 has compared the effect of transplantation of MSCs and EPO gene-modified MSCs subretinally in a rat model of retinal degeneration.…”

Section: Future Directionsmentioning

confidence: 99%

Revisiting the role of erythropoietin for treatment of ocular disorders

Ding

Leow

Munisvaradass

et al. 2016

Eye

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Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.

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Section: Future Directionsmentioning

confidence: 99%

Revisiting the role of erythropoietin for treatment of ocular disorders

Ding

Leow

Munisvaradass

et al. 2016

Eye

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“…Retroviral vectors and infection protocols were performed as previously described [29]. Lucinfected UC-MSCs and BM-MSCs were selected by adding G418 (Gibco) at 0.5 mg/mL to the medium for 10 days.…”

Section: In Vivo Live Cell-tracking Analysismentioning

confidence: 99%

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

Todeschi

Backly

Capelli

et al. 2015

Stem Cells and Development

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Umbilical cord mesenchymal stem cells (UC-MSCs) show properties similar to bone marrow mesenchymal stem cells (BM-MSCs), although controversial data exist regarding their osteogenic potential. We prepared clinical-grade UC-MSCs from Wharton's Jelly and we investigated if UC-MSCs could be used as substitutes for BM-MSCs in muscoloskeletal regeneration as a more readily available and functional source of MSCs. UCMSCs were loaded onto scaffolds and implanted subcutaneously (ectopically) and in critical-sized calvarial defects (orthotopically) in mice. For live cell-tracking experiments, UC-MSCs were first transduced with the luciferase gene. Angiogenic properties of UC-MSCs were tested using the mouse metatarsal angiogenesis assay. Cell secretomes were screened for the presence of various cytokines using an array assay. Analysis of implanted scaffolds showed that UC-MSCs, contrary to BM-MSCs, remained detectable in the implants for 3 weeks at most and did not induce bone formation in an ectopic location. Instead, they induced a significant increase of blood vessel ingrowth. In agreement with these observations, UC-MSC-conditioned medium presented a distinct and stronger proinflammatory/chemotactic cytokine profile than BM-MSCs and a significantly enhanced angiogenic activity. When UC-MSCs were orthotopically transplanted in a calvarial defect, they promoted increased bone formation as well as BM-MSCs. However, at variance with BM-MSCs, the new bone was deposited through the activity of stimulated host cells, highlighting the importance of the microenvironment on determining cell commitment and response. Therefore, we propose, as therapy for bone lesions, the use of allogeneic UC-MSCs by not depositing bone matrix directly, but acting through the activation of endogenous repair mechanisms.

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“…More generally, HA=TCP particles were used in this study because it had been convincingly demonstrated that among various groups of scaffolds, calcium phosphate ceramics, and, in particular, synthetic, biphasic calcium phosphates (consisting of various proportions of HA and TCP), are by far superior in promoting in vivo bone formation by osteogenic cell populations [22,[39][40][41]. For supporting bone formation, several characteristics of HA=TCP vehicles are important, such as biocompatibility, Ca=P ratio, surface roughness, macroporosity, and interconnectivity of pores [42][43][44].…”

Section: Figmentioning

confidence: 99%

In Vivo Bone Formation by Progeny of Human Embryonic Stem Cells

Kuznetsov

Cherman

Robey

2011

Stem Cells and Development

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The derivation of osteogenic cells from human embryonic stem cells (hESCs) or from induced pluripotent stem cells for bone regeneration would be a welcome alternative to the use of adult stem cells. In an attempt to promote hESC osteogenic differentiation, cells of the HSF-6 line were cultured in differentiating conditions in vitro for prolonged periods of time ranging from 7 to 14.5 weeks, followed by in vivo transplantation into immunocompromised mice in conjunction with hydroxyapatite=tricalcium phosphate ceramic powder. Twelve different medium compositions were tested, along with a number of other variables in culture parameters. In differentiating conditions, HSF-6-derived cells demonstrated an array of diverse phenotypes reminiscent of multiple tissues, but after a few passages, acquired a more uniform, fibroblast-like morphology. Eight to 16 weeks post-transplantation, a group of transplants revealed the formation of histologically proven bone of human origin, including broad areas of multiple intertwining trabeculae, which represents by far the most extensive in vivo bone formation by the hESC-derived cells described to date. Knockout-Dulbecco's modified Eagle's medium-based media with fetal bovine serum, dexamethasone, and ascorbate promoted more frequent bone formation, while media based on a-modified minimum essential medium promoted teratoma formation in 12-to 20-week-old transplants. Transcription levels of pluripotency-related (octamer binding protein 4, Nanog), osteogenesis-related (collagen type I, Runx2, alkaline phosphatase, and bone sialoprotein), and chondrogenesis-related (collagen types II and X, and aggrecan) genes were not predictive of either bone or teratoma formation. The most extensive bone was formed by the strains that, following 4 passages in monolayer conditions, were cultured for 23 to 25 extra days on the surface of hydroxyapatite=tricalcium phosphate particles, suggesting that coculturing of hESC-derived cells with osteoconductive material may increase their osteogenic potential. While none of the conditions tested in this study, and elsewhere, ensured consistent bone formation by hESC-derived cells, our results may elucidate further directions toward the construction of bone on the basis of hESCs or an individual's own induced pluripotent stem cells.

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Enhanced engraftment of EPO-transduced human bone marrow stromal cells transplanted in a 3D matrix in non-conditioned NOD/SCID mice

Cited by 45 publications

References 20 publications

Revisiting the role of erythropoietin for treatment of ocular disorders

Revisiting the role of erythropoietin for treatment of ocular disorders

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

In Vivo Bone Formation by Progeny of Human Embryonic Stem Cells

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