In Utero Fetal Liver Cell Transplantation without Toxic Irradiation Alleviates Lysosomal Storage in Mice with Mucopolysaccharidosis Type VII

Barker, Jane E.; Deveau, Sue; Lessard, Mark D.; Hamblen, Nancy; Vogler, Carole; Levy, Beth

doi:10.1006/bcmd.2001.0453

Cited by 22 publications

(20 citation statements)

References 47 publications

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“…Although it was reported that monocyte contribution to tissue macrophages varies from no contribution for microglias and Langerhans cells to complete monocyte origin for intestinal lamina propria macrophages (Sieweke and Allen 2013), we confirmed the presence of donor cells in the brain as reported in previous studies (Fig. 4) (Barker et al 2001(Barker et al , 2003a. 20.2, 23.5 12.0, 13.7 Homo (n = 13) 16.7 ± 1.7 11.0 ± 0.5…”

Section: Discussionsupporting

confidence: 91%

“…In utero hematopoietic cell transplantation has previously been performed in MPSVII mice, but a lifelong engraftment of allogeneic donor cells and a complete cure of the phenotype have not been achieved (Barker et al 2001(Barker et al , 2003bCasal 2001). For a successful long-term engraftment of allogeneic cells in IUHCT, the initial engraftment rate should be above the threshold of 1.8% (Durkin et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Partial rescue of mucopolysaccharidosis type VII mice with a lifelong engraftment of allogeneic stem cells in utero

Ihara

Umezawa

Onami

et al. 2015

Congenital Anomalies

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In utero hematopoietic cell transplantation (IUHCT) has been performed in Mucopolysaccharidosis Type VII (MPSVII) mice, but a lifelong engraftment of allogeneic donor cells has not been achieved. In this study, we sought to confirm a lifelong engraftment of allogeneic donor cells immunologically matched to the mother and to achieve partial rescue of phenotypes in the original MPSVII strain through IUHCT by intravenous injection. We performed in vitro fertilization in a MPSVII murine model and transferred affected embryos to ICR/B6-GFP surrogate mothers in cases where fetuses receiving IUHCT were all homozygous. Lineage-depleted cells from ICR/B6-GFP mice were injected intravenously at E14.5. Chimerism was confirmed by flow cytometry at 4 weeks after birth, and β-glucuronidase activity in serum and several phenotypes were assessed at 8 weeks of age or later. Donor cells in chimeric mice from ICR/B6-GFP mothers were detected at death, and were confirmed in several tissues including the brains of sacrificed chimeric mice. Although the serum enzyme activity of chimeric mice was extremely low, the engraftment rate of donor cells correlated with enzyme activity. Furthermore, improvement of bone structure and rescue of reproductive ability were confirmed in our limited preclinical study. We confirmed the lifelong engraftment of donor cells in an original immunocompetent MPSVII murine model using intravenous IUHCT with cells immunologically matched to the mother without myeloablation, and the improvement of several phenotypes.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Partial rescue of mucopolysaccharidosis type VII mice with a lifelong engraftment of allogeneic stem cells in utero

Ihara

Umezawa

Onami

et al. 2015

Congenital Anomalies

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“…We have developed a completely nonablative technology for neonatal transplantation (32) and have used it successfully (33) in the MPSVII mouse model of Sly syndrome (34). The advantages include: early treatment; dissemination of donor GUSBϩ macrophage progeny to bone, BM, visceral organs, and brain; provision of sufficient enzyme to alleviate lysosomal storage by crosscorrecting host cells; 3-fold increase in the average lifespan; alleviation of functional defects; and lack of immune response to the GUSB that is provided by donor cells (35). As noted above, ERT in the null host can cause anaphylactic shock in most animal models and must be managed in human recipients.…”

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confidence: 99%

Electrocardiographic and other cardiac anomalies in β-glucuronidase-null mice corrected by nonablative neonatal marrow transplantation

Schuldt

Hampton

Chu

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Cardiovascular manifestations of lysosomal storage disease (LSD) are a significant health problem for affected patients. Infantileonset cardiac disease, because of its rapid progression, is usually treated symptomatically. Therapy in older patients includes valve replacement and bone marrow (BM) transplantation, both of which are life threatening in the already debilitated patients. Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in ␤-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly syndrome), develop progressive LSD unless provided with GUSB early in life. The BM recipients retained GUSB؉ donor cells in the peripheral blood and heart until necropsy at >11 months of age. The enzyme ␤-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (P ‫؍‬ 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart͞body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of LSD.

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“…Since neurological injury from certain storage diseases may begin well before birth, IU HSC transplantation may merit consideration for such diseases. In preclinical studies, in utero transplantation with fetal liver cells (as an alternative to cord blood) has been reported to alleviate many of the effects of mucopolysaccharidosis type VII in mice (Barker et al, 2001). …”

Section: Metabolic Storage Disordersmentioning

confidence: 99%

Cell‐based therapies for birth defects: A role for adult stem cell plasticity?

Fang

Poulsom

2003

Birth Defects Research Pt C

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Cell therapy can offer a reasonable approach to the treatment of specific birth defects, particularly those for which hematopoietic stem cells (HSCs) can be used to restore (even partially) the number of cells, protein levels, or enzyme activity. Relatively few clinical experiences have been published on this subject, but when a natural selective advantage exists for the cell graft, a degree of "rescue" is possible. Strategies have been developed to confer a selective advantage through genetic engineering of donor cells, and this approach may prove valuable in the treatment of birth defects, as it is in hematological malignancy. Stem cell (SC) plasticity, or transdifferentiation, may offer another route for delivery of cells to established or developing organs. A wide variety of studies support the concept that adult tissue-specific SCs can, if displaced from their normal niche to another, be reprogrammed to produce cell types appropriate to their new environment. Clinical observations reveal that persistent tissue microchimerism develops not only in blood lineages after transfusion, but also in thyroid follicular epithelium via transplacental exchange. In addition, hepatic and renal parenchyma also become chimeric following allografts or bone marrow transplantation (BMT). Experimental models indicate that a renal glomerulosclerosis phenotype can be transferred by grafting whole BM, and that a severe liver disorder in fah-/- mice can be overcome by grafting HSCs and then exerting a selection pressure. It may be possible in the future to exploit the ability of adult SCs to contribute to diverse tissues; however, our understanding of the processes involved is at a very early stage.

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In Utero Fetal Liver Cell Transplantation without Toxic Irradiation Alleviates Lysosomal Storage in Mice with Mucopolysaccharidosis Type VII

Cited by 22 publications

References 47 publications

Partial rescue of mucopolysaccharidosis type VII mice with a lifelong engraftment of allogeneic stem cells in utero

Partial rescue of mucopolysaccharidosis type VII mice with a lifelong engraftment of allogeneic stem cells in utero

Electrocardiographic and other cardiac anomalies in β-glucuronidase-null mice corrected by nonablative neonatal marrow transplantation

Cell‐based therapies for birth defects: A role for adult stem cell plasticity?

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