Evaluating a mass balance model for soil trace metals using the historical data from the King's Kitchen Garden (Versailles, France).

The mass balance of reconstituted Cd, Cu, Pb and Zn fluxes from 1683 to 2021 was compared to the current levels of the soil used only for vegetable production in the King's Kitchen Garden in Versailles (France). This comparison was made on the basis of 4 scenarios of organic matter application in the 18th and 19th centuries and by an uncertainty analysis over the entire period. The topsoil contamination falls within that of French kitchen gardens. Modelling of past fluxes predicted the correct trend (an increase) and order of magnitude of the soil metal contents. It produced a relatively accurate evaluation of the Cu and Zn contents. The model underestimated the Pb contents by about 80%, revealing a large and unknown source of soil contamination by this metal. The calculation overestimated the current Cd levels by about 100%, probably due to various biases, for example on atmospheric fallout or the composition of organic amendments. This assessment shows that modelling the mass balance of trace metal fluxes can be used to predict the long-term trend in the levels of these elements in cultivated soils, providing the input data are chosen according to realistic scenarios.

Myoblasts derived from normal hESCs and dystrophic hiPSCs efficiently fuse with existing muscle fibers following transplantation.

Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) have an endless self-renewal capacity and can theoretically differentiate into all types of lineages. They thus represent an unlimited source of cells for therapies of regenerative diseases, such as Duchenne muscular dystrophy (DMD), and for tissue repair in specific medical fields. However, at the moment, the low number of efficient specific lineage differentiation protocols compromises their use in regenerative medicine. We developed a two-step procedure to differentiate hESCs and dystrophic hiPSCs in myogenic cells. The first step was a culture in a myogenic medium and the second step an infection with an adenovirus expressing the myogenic master gene MyoD. Following infection, the cells expressed several myogenic markers and formed abundant multinucleated myotubes in vitro. When transplanted in the muscle of Rag/mdx mice, these cells participated in muscle regeneration by fusing very well with existing muscle fibers. Our findings provide an effective method that will permit to use hESCs or hiPSCs for preclinical studies in muscle repair.

AG490 improves the survival of human myoblasts in vitro and in vivo.

Cell therapies consist in transplanting healthy cells into a disabled tissue with the goal to repopulate it and restore its function at least partially. In muscular diseases, most of the time, myoblasts are chosen for their expansion capacity in culture. Nevertheless, cell transplantation has limitations, among them, death of the transplanted cells, during the days following the graft. One possibility to counteract this problem is to enhance the proliferation of the transplanted myoblasts before their fusion with the existing muscle fibers. AG490 is a specific inhibitor of janus tyrosine kinase 2 (JAK2). The hypothesis is to block myoblast differentiation with AG490, thus permitting their proliferation. The inhibition of myoblast fusion by AG490 was confirmed in this study by gene expression and with a myosin heavy chain staining (MyHC). Moreover, cell survival was estimated by flow cytometry. AG490 was found to protect myoblasts in vitro from apoptosis induced by H(2)O(2) or by preventing attachment of cells to their substrate. Finally, in an in vivo model of muscle regeneration, when AG490 was coinjected with the myoblasts their survival was increased by 45% at 5 days after their transplantation.