Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases

Omer N. Koç, Charles Peters, Patrick Aubourg, Shrini Raghavan, Stephanie Dyhouse, Rita Degasperi, Edwin H. Kolodny, Yoav Benyoseph, Stanton L. Gerson, Hillard M. Lazarus, Arnold I. Caplan, Paul A. Watkins, William Krivit

Research output: Contribution to journalArticlepeer-review

Abstract

Human bone marrow contains mesenchymal stem cells (MSCs) that can differentiate into various cells of mesenchymal origin. We developed an efficient method of isolating and culture expanding a homogenous population of MSCs from bone marrow and determined that MSCs express α-L-iduronidase, arylsulfatase-A and B, glucocerebrosidase, and adrenoleukodystrophy protein. These findings raised the possibility that MSCs may be useful in the treatment of storage disorders. To determine if donor derived MSCs are transferred to the recipients with lysosomal or peroxisomal storage diseases by allogeneic hematopoietic stem cell (HSC) transplantation, we investigated bone marrow derived MSCs of 13 patients 1-14 years after allogeneic transplantation. Highly purified MSCs were genotyped either by fluorescence in situ hybridization using probes for X and Y-chromosomes in gender mis- matched recipients or by radiolabeled PCR amplification of polymorphic simple sequence repeats. Phenotype was determined by the measurement of disease specific protein/enzyme activity in purified MSCs. We found that MSCs isolated from recipients of allogeneic HSC transplantation are not of donor genotype and have persistent phenotypic defects despite successful donor type hematopoietic engraftment. Whether culture expanded normal MSCs can be successfully transplanted into patients with storage diseases and provide therapeutic benefit needs to be determined.

Original languageEnglish (US)
Pages (from-to)1675-1681
Number of pages7
JournalExperimental Hematology
Volume27
Issue number11
DOIs
StatePublished - Nov 1 1999

Keywords

  • Allogenic bone marrow
  • Hematopoietic stem cell
  • Mesenchymal stem cell
  • Storage disease
  • Stromal cells

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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