STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS welcomes original articles and concise reviews describing basic laboratory investigations of stem cells and the translation of their clinical aspects of characterization and manipulation from the bench to patient care. The journal covers all aspects of stem cells embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; stem cell technology: epigenetics, genomics, proteomics, and metabonomics; cancer stem cells; translational and clinical research; and regenerative medicine.

The purpose was to investigate the effect of a 16-wk intrahospital supervised conditioning program including both resistance and aerobic training and a 20-wk detraining period on measures of aerobic fitness, muscular strength, functional mobility, ankle range of motion, and quality of life (QOL) in children receiving treatment for acute lymphoblastic leukemia (ALL). Seven children (four boys, three girls; age: 5.1 ± 1.2 yr, body mass: 24.0 ± 5.8 kg, height: 114.6 ± 7.7 cm) in the maintenance phase of treatment against ALL performed three sessions per week for 16 wk of resistance (one set of 8-15 repetitions of 11 exercises) and aerobic training (30 min at > 70% HRmax) followed by 20 wk of detraining where no structured exercise program was performed. Before training, after training, and after detraining, a treadmill test determining V˙O2peak and ventilator threshold (VT), muscular strength (6RM), functional mobility (timed up and down stairs test, time up and go 3-m and 10-m tests), passive and dynamic ankle range of motion, and self-reported quality of living were determined. After training, significant increases in V˙O2peak, VT, upper- and lower-body muscular strength, and all measures of functional mobility were shown (P < 0.05). Muscular strength was well maintained (significantly greater than before training and no significant decrease from after training) during detraining, whereas V˙O2peak, VT, and functional mobility (not significantly different from before training but no significant decrease from after training) were only partially retained. Young children in the maintenance phase of treatment against ALL can safely perform both aerobic and resistance training. Training results in significant increases in measures of aerobic fitness, strength, and functional mobility. During detraining, strength and functional mobility are well maintained, whereas V˙O2peak and VT are partially maintained.

Importance of the field: In the last decade, knowledge of mesenchymal stem cells (MSCs) has evolved rapidly; their immunomodulatory properties and paracrine interactions with specific cell types in damaged tissues and promising results in some clinical applications have made these cells an attractive option for the treatment of certain diseases.Areas covered in this review: We present some relevant methodological issues and biological properties of MSCs, as well as clinical applications of MSC therapies with particular emphasis in the treatment of graft versus host disease (GVHD), complex perianal fistula and refractory metastatic neuroblastoma. Other topical aspects relevant to the application of cellular therapies such as biosafety studies and cellular production of MSCs are also discussed in this review.What the reader will gain: The growing optimism regarding MSCs research is based on the promising results obtained in in vitro and in vivo studies. The rapid translational research with MSCs necessitate...

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse. This article reports that the expression of CD1a is mainly restricted to developing cortical thymocytes, and neither CD34⁺ progenitors nor T cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. We thus developed and preclinically validated a CD1a-specific CAR with robust and specific cytotoxicity in vitro and antileukemic activity in vivo in xenograft models of coT-ALL, using both cell lines and coT-ALL patient–derived primary blasts. CD1a-CARTs are fratricide resistant, persist long term in vivo (retaining antileukemic activity in re-challenge experiments), and respond to viral antigens. Our data support the therapeutic and safe use of fratricide-resistant CD1a-CARTs for relapsed/refractory coT-ALL. There is a Blood Commentary on this article in this issue. Key Points CD1a CARTs exhibit specific and robust cytotoxicity in vitro and in vivo using both T-ALL cell lines and primary coT-ALL cells. CD1a CARTs are fratricide resistant and exhibit long-term persistence in vivo with antileukemic activity in rechallenge experiments. Visual Abstract

The purpose of this study was to determine if an eight-week intrahospital supervised, conditioning program improves functional capacity and quality of life (QOL) in children (4 boys, 4 girls) (mean [SD] age: 10.9 [2.8] years [range: 8 - 16]) who have undergone bone marrow transplantation (BMT) for leukemia treatment within the last 12 months. A group of 8 age and gender-matched healthy children served as controls. The experimental group performed 3 weekly sessions of resistance and aerobic training inside an intra-hospital gymnasium. A significant combined effect of group and time (p < 0.05) was observed for muscle functional capacity (Timed Up and Down Stairs [TUDS] test) and peak oxygen uptake (V·O_2peak), i.e., with BMT children showing greater improvements than controls (V·O_2peak at pre- and post-training of 25.9 (8.2) and 31.1 (7.6) mL/kg/min in diseased children). Muscle strength (6 RM test for bench and leg press and seated row) also improved after training (p < 0.05) in the BMT group. Concerning QOL, a significant combined effect of group and time (p < 0.05) was also observed for children's self-report of comfort and resilience and for parents' report of their children's satisfaction and achievement. In summary, children who have received BMT experience physical and overall health benefits after a relatively short-term (8 weeks) supervised exercise training program.