Comparison of fetal and adult marrow stromal cells in osteogenesis with and without glucocorticoids.

To better understand the potential use of fetal marrow stromal cells (MSCs) in bone tissue engineering, we compared the ability of these cells with those of adult MSCs with respect to osteoblasts differentiation in the presence or absence of glucocorticoids. Cells were grown for 3-4 weeks in basal medium or supplemented with 100 nM dexamethasone (DEX, a synthetic glucocorticoid analog) or with 50 microM L-ascorbate and 10 mM glycerol-2-phosphate (AS+GP) or with AS+GP+DEX. At various time points in culture, the following parameters were compared between fetal and adult MSCs: cell morphology, cell proliferation, alkaline phosphatase activity, calcium (45Ca) uptake, von Kossa staining, and glucocorticoids receptor expression were analyzed. Compared with adult MSCs, fetal cells showed a less dramatic change to cuboidal morphology in DEX-containing media. Fetal MSCs in all media conditions showed higher proliferation rates and lower alkaline phosphatase activities (p < 0.001) than adult cells. Both fetal and adult MSCs responded similarly in DEX-containing media with respect to suppressing cell proliferation, stimulating alkaline phosphatase activity, and consistently accumulating calcium (usually higher in fetal cells) with subsequent formation of mineralized matrix when compared with cells cultured in AS+GP. Our findings further implicate the requirement of glucocorticoids in osteogenesis. In conclusion, compared with adult MSCs, fetal cells showed greater ability in sustaining cell proliferation and calcium uptake suggesting that they may be useful for bone tissue repair.

Improved outcomes in intermediate- and high-risk aggressive non-Hodgkin lymphoma after autologous hematopoietic stem cell transplantation substituting intravenous for oral busulfan in a busulfan, cyclophosphamide, and etoposide preparative regimen.

Forty-nine patients with intermediate- and high-risk aggressive non-Hodgkin lymphoma underwent autologous hematopoietic stem cell transplantation (autoHSCT) using the regimen of busulfan (Bu), cyclophosphamide (Cy), and etoposide (E) that was originally developed for allogeneic HSCT. Eighteen patients treated before 1999 received Cy 2.5 g/m2 on days -3 to -2 and E 1800 mg/m2 on day -3 after oral (PO) administration of Bu 1 mg/kg every 6 hours x 4 days for a total of 16 doses beginning on day -7. After April 1999, 31 patients similar in all pretransplantation risk assessments received the same regimen except that intravenous (IV) Bu was substituted for PO Bu and pharmacokinetic-directed (PKD) dosing was attempted to achieve an area under the concentration time curve of 1000-1500 micromol/min for each dose. Nonrelapse mortality was 28% for PO Bu patients versus 3% for the IV PKD group (P = .01, chi-square test). Actuarial 5-year overall survivals were 28% for patients who received the PO Bu regimen and 58% for patients who received the IV Bu regimen (P = .010, log-rank test), and progression-free survivals were 17% and 50%, respectively (P = .008, log-rank test). After substitution of PKD IV Bu in the BuCyE regimen, we observed lower nonrelapse mortality with increased overall and progression-free survivals in patients with intermediate- and high-risk aggressive non-Hodgkin lymphoma who underwent autoHSCT.