The majority of cells in so-called "mesenchymal stem cell" population are neither stem cells nor progenitors.

OBJECTIVES: The first-passage adherent human bone marrow fibroblast-like cell population corresponds, in terms of phenotype and three-lineage differentiation capacity (assayed in bulk culture), to commonly termed "mesenchymal stem cells". Here we determine the proportion of high proliferative capacity multipotent cells present in this population in order to estimate the proportion of cells that can or cannot be considered as stem and progenitor cells. MATERIAL AND METHODS: The single-cell cultures were established starting from human bone marrow-derived first-passage fibroblast-like cells and the proliferating clones were either transferred to secondary cultures to evaluate their further clonogenicity, or split into three wells to assess differentiation into each of the three different lineages. RESULTS: The analysis of 197 single-cell cultures from three different bone marrow donors shows that only∼40% of so-called "mesenchymal stem cells" exhibit multipotency and are capable of sustained clonogenicity in secondary cultures. CONCLUSION: Even in the first ex vivo passage under favorable conditions the majority (∼60%) of so-called "mesenchymal stem cells" are not multipotent and thus do not represent a stem cell entity.

Effect of lymphoma grafts on natural killer cell activity in AKR and C57BL/6 mice.

The natural killer (NK) cell activity of spleen suspensions was measured in AKR and C57BL/6 mice grafted either with isogeneic thymic or nonthymic lymphomas. The transplanted cells originated from lymphoid tumors (B, T, or null) which developed either spontaneously (AKR) or after radiation exposure or after injection of retroviruses (C57BL/6). The NK response was significantly enhanced in AKR and C57BL/6 mice grafted with nonthymic and with some thymic lymphoma lines maintained by in vivo passages. The increase of NK activity which took place during the first 5 days after grafting was concomitant with a hyperplasia of the spleen red pulp. Cells from invaded spleens presented a suppressive effect on NK activity. Most primary AKR thymomas and 4 out of 8 tested thymic lymphomas maintained by in vivo passage in C57BL/6 mice were not inducers. In vitro passaged lymphomas, whether AKR or C57BL/6, displayed variable capacity of stimulation which did not match those of the same in vivo maintained lines. It was found that the capacity of most cultured cells to stimulate NK activity correlated positively with the reverse transcriptase concentration of the corresponding culture media.

Thymic control in expression of natural killer activity in AKR and C57BL/6 mice.

The natural killer (NK) activity of 2-month old AKR mice was markedly depressed compared with that of C57BL/6 mice of the same age. It decreased with age in C57BL/6 mice, whereas it increased and reached a maximum at 5 months in AKR mice. When the animals developed leukaemia, NK activity completely disappeared. A considerable increase in NK activity was observed in AKR and C57BL/6 mice which had been thymectomized at 30 days of age. This activity remained at a high level for 3 months and slowly decreased afterwards. The NK activity of C57BL/6 mice fell after sublethal irradiation (1.75 Gy X 4) and did not recover within 12 weeks, except in mice restored with bone marrow (BM). When mice were thymectomized prior to radiation exposure, NK activity remained at a normal level and BM restoration resulted in a weak but significant enhancement. NK activity, which was already low in AKR mice, was not significantly modified by sublethal irradiation, whether the animals were previously thymectomized or not. In this strain, BM restoration increased the NK activity after sublethal irradiation, and a higher level was reached in thymectomized animals than in intact ones. Lethally irradiated mice restored with bone marrow displayed a high level of NK activity, which was comparable in both strains and was augmented by thymectomy. Taken together, these results indicate that spleen NK activity is, at least in part, controlled by the thymus. The increased NK activity in thymectomized animals might result from the decline or inactivation of a thymus-dependent suppressive activity. The low NK activity observed in AKR mice seems to be related to a thymus-mediated suppressive effect rather than to a defect of BM in NK precursors.