ABSTRACT

In addition to hematopoietic stem cells, bone marrow contains a second class of adult stem cells that have been referred to as fibroblastoid colony-forming units, nonhematopoietic mesenchymal stem cells or marrow stromal cells (MSCs). MSCs have attracted increasing attention for their potential use in cell and gene therapy because they have several appealing features: 1 , 2

(a) They are readily isolated from a patient by simple bone marrow aspiration under local anesthesia.

(b) They can be rapidly expanded in culture a billion-fold or more. 3 , 4 Therefore, adequate numbers of autologous cells can be generated for treatment of most conditions. The use of a patient’s own MSCs avoids the immune rejection encountered with cells from unrelated individuals.

(c) Although the cells can be expanded rapidly, they are not immortal. Therefore, they do not pose a danger of producing tumors as is seen with embryonic stem cells and with most immortal cell lines. 5

(d) MSCs can differentiate in vitro and in vivo into multiple cell lineages including osteoblasts, chondrocytes, adipocytes, myocytes, 6 pneumocytes, 7 epithelial cells 8 and early neural precursors. 9-13

(e) They can be readily transduced with genes with or without the use of viral vectors. 14-17

(f) As increasing evidence has now demonstrated, the cells have the remarkable property that they home to sites of tissue injury and repair the tissue either by differentiating into tissue-specific cell phenotypes 7 , 18-22 or by creating a milieu that increases the capacity of the endogenous cells to repair the tissue. 23-25