129 that multipotent adult progenitor cells (MAPCs), produced in vitro from bone marrow, have blood-building capacity in immune-deficient mice.
The full complement of blood cell types arises from hematopoietic stem cells (HSCs) of the bone marrow. The ability of these cells to both self-renew and to produce daughter cells capable of any hematopoietic fate makes them an attractive resource for cell replacement therapy for blood and immune disorders. However, as with adult stem cells from other tissues, long-term culturing of these cells has proven difficult.
MAPCs, on the other hand, can divide seemingly endlessly in culture. These cells, which can give rise to multiple cell types, were discovered by chance when Catherine Verfaillie's group was trying to culture another type of adult stem cell. The group now shows that MAPCs can reconstitute hematopoietic compartments in vivo just as well as HSCs. Indeed they can even give rise to HSCs themselves.
The team irradiated mice to knock out their immune cells and then injected traceable MAPCs. MAPC-derived cells were detectable in the bone marrow, spleen, peripheral blood, and lymph nodes of recipient mice and expressed appropriate B, T, and myeloid cell surface markers. Furthermore, MAPC-derived B and T cells were shown to be functional by their production of immunoglobulin and response to T cell receptor stimulus, respectively.
The team showed that MAPCs also gave rise to functional long-term HSCs. Transfer of bone marrow cells from the primary recipient mice into new irradiated mice once again led to hematopoietic reconstitution, as did a third round of transfer from these secondary mice to tertiary recipients.
None of the recipient mice in the study developed tumors, even though some of the MAPCs they received were genetically abnormal because of long-term culturing. Genotyping of the recipients' peripheral blood revealed normal karyotypes, leading Verfaillie to suggest that the genetically abnormal MAPCs were somehow cleared by the body.
The risk of tumor development from transplanted embryonic stem cells (ESCs) is an ongoing concern for their use in therapy. The potential of long-term culture followed by tumor-free cell transfer thus gives MAPCs a therapeutic advantage over both ESCs and HSCs.