Allogeneic Mesenchymal Stromal Cells (MSCs) are of Comparable Efficacy to Syngeneic MSCs for Therapeutic Revascularization in C57BKSdb/db Mice Despite the Induction of Alloantibody.

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKSdb/db mice. Phosphate-buffered saline (control group), and MSCs (1 × 106) from B6 (allogeneic group) or C57BKSdb/db (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKSdb/db mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.

Effect of docetaxel (Taxotere) on expression of radiation-induced lethal mutations in human cell lines.

PURPOSE: To investigate if docetaxel, ionizing radiation or a combination of both induces delayed cell death in selected human normal or tumour cell lines. MATERIALS AND METHODS: The initial and residual surviving fractions were determined for two malignant human colon cell lines of widely different radiosensitivity (SW 48 and HT29) and for an immortal but non-malignant human keratinocyte line (HaCaT). RESULTS: Lethal mutations were observed only after the treatment of SW48 and HaCaT cells with radiation alone. No lethal mutations were found in the HT29 cell line. No lethal mutations were observed for any cell line treated with Docetaxel and the plating efficiency of progeny was actually increased above the control level. CONCLUSION: In all cases a combination of radiation and docetaxel prevented induction of lethal mutations despite the fact that radiation alone induced lethal mutations in the SW48 and HaCaT cell lines. This suggests that the effects of pre-treating with Docetaxel are in some way blocking or inhibiting the lethal mutation pathway. There appears to be a link between the tendency of the cell line to undergo apoptosis and lethal mutation expression.

Radiobiological effects of docetaxel (Taxotere): a potential radiation sensitizer.

PURPOSE: To investigate the ability of docetaxel (Taxotere) to radiosensitize human cell lines of differing malignant status, intrinsic radiosensitivity and p53 status. MATERIALS AND METHODS: Cell survival following treatment with drug and/or radiation was determined by colony-forming assay on two malignant human colon cell lines of widely different radiosensitivity (HT29 and SW48). An immortal human keratinocyte line (HaCaT), which does not form tumours in nude mice, was used to assess the effect on non-malignant human epithelium. RESULTS: The experiments indicate that docetaxel had the greatest cytotoxic and radiosensitizing effect on the SW48 (p53wt) cell line. The degree of radiosensitization was not improved by increasing the drug concentration, although the overall cytotoxicity was increased with increasing concentrations of the two agents. Both p53mut lines were less sensitive to the drug, irrespective of their malignant potential. CONCLUSION: The results support a role for Taxotere as a weak radiosensitizer of the three cell lines tested. The p53 status and intrinsic radiosensitivity may be relevant to the mechanism.