Lentiviral-Transduced Human Mesenchymal Stem Cells Persistently Express Therapeutic Levels of Enzyme in a Xenotransplantation Model of Human Disease

Meyerrose, Todd E.; Roberts, Marie S.; Ohlemiller, Kevin K.; Vogler, Carole; Wirthlin, Louisa; Nolta, Jan A.; Sands, Mark S.

doi:10.1634/stemcells.2008-0008

Cited by 86 publications

(76 citation statements)

References 57 publications

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“…However, this response was transient and did appear to compromise neither the health of the treated mice nor the therapeutic potential of hASCs. We and others have demonstrated the effectiveness of human ASC/MSC infusion within a xenogeneic environment in murine models of lung injury [13,17,24,27,30,41], although the present study highlights for the first time the development of a short host immune response against the infused xenogeneic cells. Nevertheless, from a clinical standpoint, the immunemediated clearance of allogeneic hASCs, particularly genetically engineered hASCs, in the treated lungs should reduce the safety concerns regarding the persistence of these implanted cells longer than required.…”

Section: Cd8mentioning

confidence: 59%

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Martínez-González

Cruz

Moreno

et al. 2014

Stem Cells and Development

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Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1 · 10 6 cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the APinjured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA.

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Section: Cd8mentioning

confidence: 59%

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Martínez-González

Cruz

Moreno

et al. 2014

Stem Cells and Development

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“…The potentialities of this kind of approach are currently under consideration in several fields, as demonstrated by the growing list of publications on this topic (Corsten and Shah 2008;Granero-Molto et al 2008;Liu et al 2008;Meyerrose et al 2008;Xu and Liu 2008;and others). The rationale in the application of MSCT to RANKL-dependent ARO is that in this way the patient would receive the specific precursor cells able to differentiate into normal osteoblasts, producing in situ the cytokine RANKL, which is defective in the recipient, and thus allowing the differentiation of osteoclast precursors into normal, functional cells.…”

Section: Discussionmentioning

confidence: 99%

Prognostic potential of precise molecular diagnosis of Autosomal Recessive Osteopetrosis with respect to the outcome of bone marrow transplantation

et al. 2008

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Hematopoietic stem cell transplantation (HSCT) is often the only practical approach to fatal genetic defects. One of the first pathologies which HSCT was applied to was Autosomal Recessive Osteopetrosis (ARO), a rare genetic bone disease in which a deficit in bone resorption by osteoclasts leads to increased bone density and secondary defects. The disease is often lethal early in life unless treated with HSCT. In utero transplantation (IUT) of the oc/oc mouse, reproducing the clinical features of a subset of ARO, has demonstrated that the quality of life and the survival of transplanted animals are greatly improved, suggesting that a similar protocol could be applied to humans. However, recently the dissection of the molecular bases of the disease has shown that ARO is genetically heterogeneous and has revealed the presence of subsets of patients which do not benefit from HSCT. This observation highlights the importance of molecular diagnosing ARO to identify and establish the proper therapies for a better prognosis. In particular, on the basis of experimental results in murine models, efforts should be undertaken to develop approaches such as IUT and new pharmacological strategies.

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“…in a non-obese diabetic-severe combined immunodeficiency model of mucopolysaccharidosis type VII, expressed therapeutic levels of protein and persisted for at least 4 months, with no apparent immune response. 65 If immune tolerance elicited by MSCs in vivo is not completely reliable, an option is to enclose gene-modified MSC into devices (Figure 1e) that protect them from the host immune system and at the same time allow entry of nutrients and oxygen and exit of the therapeutic protein. 66 Goren et al 67 designed alginate-poly-L-lysine microcapsules that can encapsulate human MSCs for extended periods.…”

Section: Stem Cell-based Gene Delivery L Sanz Et Almentioning

confidence: 99%

Non-hematopoietic stem cells as factories for in vivo therapeutic protein production

et al. 2011

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Lentiviral-Transduced Human Mesenchymal Stem Cells Persistently Express Therapeutic Levels of Enzyme in a Xenotransplantation Model of Human Disease

Abstract: ABSTRACT

Cited by 86 publications

References 57 publications

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Prognostic potential of precise molecular diagnosis of Autosomal Recessive Osteopetrosis with respect to the outcome of bone marrow transplantation

Non-hematopoietic stem cells as factories for in vivo therapeutic protein production

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