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Mesenchymal Stem Cells

Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)

Bone Marrow Transplantation volume 30, pages 215–222 (2002)Cite this article

Abstract

Patients with Hurler syndrome (mucopolysaccharidosis type-IH) and metachromatic leukodystrophy (MLD) develop significant skeletal and neurologic defects that limit their survival. Transplantation of allogeneic hematopoietic stem cells results in partial correction of the clinical manifestations. We postulated that some of these defects may be corrected by infusion of allogeneic, multipotential, bone marrow-derived mesenchymal stem cells (MSC). Patients with Hurler syndrome (n = 5) or MLD (n = 6) who previously underwent successful bone marrow transplantation from an HLA-identical sibling were infused with 2–10 × 106/kg MSCs, isolated and expanded from a bone marrow aspirate of the original donor. There was no infusion-related toxicity. In most recipients culture-purified MSCs at 2 days, 30–60 days and 6–24 months after MSC infusion remained of host type. In two patients the bone marrow-derived MSCs contained 0.4 and 2% donor MSCs by FISH 60 days after MSC infusion. In four patients with MLD there were significant improvements in nerve conduction velocities after MSC infusion. The bone mineral density was either maintained or slightly improved in all patients. There was no clinically apparent change in patients’ overall health, mental and physical development after MSC infusion. We conclude that donor allogeneic MSC infusion is safe and may be associated with reversal of disease pathophysiology in some tissues. The role of MSCs in the management of Hurler syndrome and MLD should be further evaluated.

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Acknowledgements

This work was supported by NIH, NCI R21CA82531 (PI: ON Koç). We thank Ms Stephanie Dyhouse and Ms Faraha Brewer for culture of donor MSCs, Ms Emese Szekely for analysis of recipient bone marrow aspirate samples. We thank Drs Edwin H Kolodny and Srini Rhagavan for the enzyme measurements in normal donor MSCs. The clinical trial was conducted at the General Clinical Research Center of the Case Western Reserve University.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA

    ON Koç, SL Gerson & HM Lazarus

  2. Department of Neurology, University of Minnesota, Minneapolis, MN, USA

    J Day

  3. Pediatrics and Comprehensive Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA

    M Nieder

  4. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    W Krivit

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  1. ON Koç
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  2. J Day
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  4. SL Gerson
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  5. HM Lazarus
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  6. W Krivit
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Koç, O., Day, J., Nieder, M. et al. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30, 215–222 (2002). https://doi.org/10.1038/sj.bmt.1703650

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  • DOI: https://doi.org/10.1038/sj.bmt.1703650

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