Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta

@article{Horwitz1999TransplantabilityAT,
  title={Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta},
  author={Edwin M. Horwitz and D. J. Prockop and Lorraine A. Fitzpatrick and Winston W. K. Koo and Patricia L. Gordon and Michael D. Neel and Michael D. Sussman and Paul J. Orchard and Jeffrey C. Marx and Reed E. Pyeritz and Malcolm K. Brenner},
  journal={Nature Medicine},
  year={1999},
  volume={5},
  pages={309-313}
}
In principle, transplantation of mesenchymal progenitor cells would attenuate or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with osteogenesis imperfecta, a genetic disorder in which osteoblasts produce defective type I collagen, leading to osteopenia, multiple fractures, severe bony deformities and considerably shortened… 

Paper Mentions

Interventional Clinical Trial
This is a study to evaluate the safety and effectiveness of repeated Mesenchymal Stromal Cells (MSC) infusions to patients with Type II or III osteogenesis imperfecta (OI… 
ConditionsOsteogenesis Imperfecta Type II, Osteogenesis Imperfecta Type III
InterventionBiological
Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta.
TLDR
Clinical responses of the first children to undergo allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta, a genetic disorder characterized by defective type I collagen, osteopenia, bone fragility, severe bony deformities, and growth retardation, are described.
Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone
TLDR
Allogeneic mesenchymal cells offer feasible posttransplantation therapy for osteogenesis imperfecta and likely other disorders originating in mesenchyal precursors, including bone, cartilage, and muscle.
Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms.
TLDR
It is shown that non-(plastic)-adherent bone marrow cells (NABMCs) are more potent osteoprogenitors than MSCs in mice, and in a murine model of OI, it is demonstrated that as the donor NABMCs differentiate to osteoblasts, they contribute normal collagen to the bone matrix.
Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells with Bone Marrow Transplantation Improved Osteogenesis in Infants with Severe Hypophosphatasia
TLDR
It is suggested that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP, and allogeneic MSC-based therapy would be useful for Patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.
Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.
Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human
Amelioration of a mouse model of osteogenesis imperfecta with hematopoietic stem cell transplantation: microcomputed tomography studies.
TLDR
Findings strongly support the concept that hematopoietic stem cells generate bone cells using bone marrow (BM) cell transplantation in a mouse model of osteogenesis imperfecta and suggest therapeutic potentials of HSCs in OI.
Engraftment of skeletal progenitor cells by bone‐directed transplantation improves osteogenesis imperfecta murine bone phenotype
TLDR
Locally transplanted BMSCs can improve cortical structure and strength, and persist as continued source of osteoblast progenitors in the OIM mouse for at least 6 months, and local transplantation of B MSCs increased cortical thickness, the polar moment of inertia, bone strength and stiffness 3 months post‐transplantation.
Replacement of recipient stromal/mesenchymal cells after bone marrow transplantation using bone fragments and cultured osteoblast-like cells.
  • R. Cahill, O. Jones, +5 authors R. Good
  • Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2004
TLDR
This protocol is the first to test the use of bone fragments as an ideal vehicle to transplant such cells residing in the bone core and was able to achieve high levels of stroma cell engraftment as defined by molecular analyses of bone biopsy specimens.
Clinical and laboratory studies of mesenchymal stem cells in long bone fracture nonunion
TLDR
Results indicate a functional defect in proliferative capacity of MSCs in nonunion, which points towards a generalized systemic effect of the nonunion state on MSC dynamics, which should be further explored in future.
Fetal Mesenchymal Stem-Cell Engraftment in Bone after In Utero Transplantation in a Patient with Severe Osteogenesis Imperfecta
TLDR
The authors’ findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 38 REFERENCES
Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant.
TLDR
Because osteoblasts were still of recipient origin post-BMT, this suggests that functional osteoclasts, due to the replacement of hematopoeitic cells, provided a local microenvironment in vivo triggering the differentiation and/or recruitment of a limited number of functional osteoblast.
Successful bone-marrow transplantation for infantile malignant osteopetrosis.
TLDR
Allogeneic bone-marrow transplantation appears to be the treatment of choice in this fatal disorder and vision, hearing, growth, and development were progressively improving 16 months after transplantation.
Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2.
TLDR
It is demonstrated that stem cells within the stromal compartment of bone marrow are capable of rapidly acquiring osteoblast features and a potential role for glucocorticoids in combination with BMP-2 and vitamin D in stages of osteogenic development is suggested.
Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta.
  • R. Pereira, M. O'Hara, +6 authors D. Prockop
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
TLDR
The results support previous suggestions that marrow stromal cells or related cells in marrow serve as a source for continual renewal of cells in a number of nonhematopoietic tissues.
Repair of bone defects with marrow cells and porous ceramic. Experiments in rats.
TLDR
Results indicated that composite grafts of porous calcium phosphate ceramics and marrow cells may be clinically applicable to enhance osteogenesis and osteoconduction.
Cellular expression of bone‐related proteins during in vitro osteogenesis in rat bone marrow stromal cell cultures
TLDR
The studies indicate that the bone marrow stromal cell system is a useful model to study the temporal and spatial expression of bone‐related proteins during osteogenesis and formation, mineralization, and maturation of bone nodules.
The osteogenic potential of culture-expanded rat marrow mesenchymal cells assayed in vivo in calcium phosphate ceramic blocks.
TLDR
Porous ceramic provides an excellent delivery vehicle for cells that are capable of osteogenic expression and suggest that the composite graft of marrow-derived mesenchymal cells and porous ceramic may be useful for repair of massive bone defects.
Osteoprogenitor Cells as Targets for Ex Vivo Gene Transfer
  • J. Onyia, D. Clapp, H. Long, J. Hock
  • Biology, Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 1998
TLDR
This is one of the first demonstrations of successful transplantation of clonal osteoprogenitors to their site of origin in bone and it may be possible to use these cells to target genes to bone for therapeutic use in skeletal and hematopoietic diseases.
Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice.
TLDR
It is demonstrated that mesenchymal precursor cells from marrow that are expanded in culture can serve as long-lasting precursors for mesenchcyal cells in bone, cartilage, and lung and suggest that cells may be particularly attractive targets for gene therapy ex vivo.
Cyclic administration of pamidronate in children with severe osteogenesis imperfecta.
TLDR
In children with severe osteogenesis imperfecta, cyclic administration of intravenous pamidronate improved clinical outcomes, reduced bone resorption, and increased bone density.
...
1
2
3
4
...