Abstract
The potential of adult mesenchymal stem cells (MSCs) to differentiate to diverse cell types in vitro and in vivo offers outstanding opportunities to use these cells as therapeutic agents. The biological characteristics of MSCs isolated from two distinct tissues, bone marrow and adipose tissue were evaluated in vitro and in vivo. MSCs derived from human and non-human primate (rhesus monkey) tissue sources were compared. The data indicate that MSCs isolated from rhesus bone marrow (rBMSCs) and human adipose tissue (hASCs) had more similar biologic properties than MSCs ofrhesus adipose tissue (rASCs) and human bone marrow MSCs (hBMSCs). Analyses of in vitro growth kinetics revealed shorter doubling time for rBMSCs and hASCs. rBMSCs and hASCs underwent significantly more population doublings than the other MSCs. MSCs from all sources showed a marked decrease in telomerase activity over extended culture; however they maintained their mean telomere length. All of the MSCs expressed embryonic stem cell markers, Oct-4, Rex-1 and Sox-2 for at least 10 passages. Early populations of MSCs types showed similar multilineage differentiation capability. However, only the rBMSCs and hASCs retain greater differentiation efficiency at higher passages. Overall in vitro characterization of MSCs from these two species and tissue sources revealed a high level of common biologic properties. The bone marrow and adipose tissue derived MSCs were then compared for the plasticity in vivo. In a time course study, the two types of MSCs were transplanted into the lateral ventricles of NIHIII immune deficient mice. The migration and engraftment of MSCs have been evaluated on 2, 4, and 6 weeks post engraftment. Our results indicated that while both cell types engrafted in multiple regions throughout the brain, the adipose tissue derived MSCs persisted in the brain for longer periods of time. The adipose tissue derived MSCs were detected up to six weeks post-transplantation. Since there is no ethical limitation on using adult stem cells, the results of this study suggest that adipose tissue and bone marrow will prove to be important sources of pluripotent stem cells.
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