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Human Mesenchymal Stem Cells Persist, Demonstrate Site-Specific Multipotential Differentiation, and Are Present in Sites of Wound Healing and Tissue Regeneration after Transplantation into Fetal Sheep

https://doi.org/10.1006/bcmd.2001.0424Get rights and content

Abstract

ABSTRACT

Prenatal transplantation of stem cells is an exciting frontier for the treatment of many congenital diseases. The fetus may be an ideal recipient for stem cells, as it is immunologically immature and has rapidly proliferating cellular compartments that may support the engraftment of transplanted cells. Mesenchymal stem cells (MSC), given their ability to differentiate into multiple cell types, could potentially be used to treat diseases such as osteogenesis imperfecta, muscular dystrophy, and other mesenchymal disorders that can be diagnosed in utero. We have shown, using a human–sheep in utero xenotransplantation model, that human MSC have the ability to engraft, undergo site-specific differentiation into multiple cell types, and survive for more than 1 year in fetal lamb recipients. In addition, in this model MSC-derived cells appear to be present in increased numbers in wounded or regenerating tissues. This observation warrants further studies of the biology of MSCs following systemic or site-directed transplantation.

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    Citation Excerpt :

    Variability in culture characteristics affects the cellular differentiation, which could be attributable to the available micro-environment. In utero transplantation of autologous or xenogenic MSCs in ovine model led to their site-specific differentiation even after development of immune system in the foetus (Liechty et al., 2000; Mackenzie and Flake, 2001; Shaw et al., 2011), which supports the role of local milieu in cellular differentiation and indicates the possibility of lack of the cell immunogenicity in ovine MSCs. Homing of the oMSCs to wounded or regenerating tissues conformed to the established characteristics of the species specific MSCs (Mackenzie and Flake, 2001).

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Communicated by M. Lichtman, M.D., 05/08/01

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Correspondence and reprint requests to: Alan W. Flake, The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. Fax: (215) 590-3324. E-mail: [email protected].

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