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

Human bone marrow contains mesenchymal stem cells (MSCs) that can different iate into various cells of mesenchymal origin, We developed an efficient me thod of isolating and culture expanding a homogenous population of MSCs fro m bone marrow and determined that MSCs express alpha-L-iduronidase, arylsul fatase-A and B, glucocerebrosidase, and adrenoleukodystrophy protein. These findings raised the possibility that MSCs may be useful in the treatment o f 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. H ighly purified MSCs were genotyped either by fluorescence in situ hybridiza tion 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/e nzyme activity in purified MSCs. We found that MSCs isolated from recipient s of allogeneic HSC transplantation are not of donor genotype and have pers istent phenotypic defects despite successful donor type hematopoietic engra ftment, Whether culture expanded normal MSCs can be successfully transplant ed into patients with storage diseases and provide therapeutic benefit need s to be determined. (C) 1999 International Society for Experimental Hematol ogy. Published by Elsevier Science Inc.