Mesenchymal stem cells (MSCs) are being widely studied as potential cell therapy agents due to their immunomodulatory properties, which have been established by in vitro studies and in several clinical trials. Within this context, mesenchymal stem cell therapy appears to hold substantial promise, particularly in the treatment of conditions involving autoimmune and inflammatory components. Nevertheless, many research findings are still contradictory, mostly due to difficulties in characterization of the effects of MSCs in vivo. The purpose of this review is to report the mechanisms underlying mesenchymal stem cell therapy for acute graft-versus-host disease, particularly with respect to immunomodulation, migration, and homing, as well as report clinical applications described in the literature.

No abstract

Mesenchymal stem cells (MSC) are considered multipotent stromal, non-hematopoietic cells with properties of self-renovation and differentiation. Optimal conditions for culture of MSC have been under investigation. The oxygen tension used for cultivation has been studied and appears to play an important role in biological behavior of mesenchymal cells. The aim is characterize MSC in hypoxia and normoxia conditions comparing their morphological and functional characteristics. Bone marrow-derived mesenchymal stem cells obtained from 15 healthy donors and cultured. MSC obtained from each donor were separated into two cultivation conditions normoxia (21% O ) and hypoxia (three donors at 1%, three donors at 2%, five donors at 3%, and four donors at 4% O ) up to second passage. MSC were evaluated for proliferation, differentiation, immunophenotyping, size and cell complexity, oxidative stress, mitochondrial activity, and autophagy. Culture conditions applied did not seem to affect immunophenotypic features and cellular plasticity. However, cells subjected to hypoxia showed smaller size and greater cellular complexity, besides lower proliferation (P < 0.002). Furthermore, cells cultured in low O tension had lower mitochondrial activity (P < 0.03) and a reduced tendency to autophagy, although oxidative stress did not vary among groups (P < 0.39). Oxygen tension seems to be a key regulator of cellular adaptation in vitro, and metabolic effects underlying this variable remain undescribed. Heterogeneity or even lack of results on the impact of oxygen concentration used for expanding MSC highlights the need for further research, in order to optimize conditions of cultivation and expansion and achieve greater safety and therapeutic efficacy. J. Cell. Biochem. 118: 3072-3079, 2017. © 2017 Wiley Periodicals, Inc.

Mesenchymal stromal cells (MSC) have shown their benefits in graft-versus-host disease (GVHD), with five unsettled matters: 1) MSCs expansion in medium with Fetal Bovine Serum (FBS) and its risk of xenoreaction;2) The number of cells indicated for therapy that is relatively high, with the need to optimize the expansion, number and time wise; 3) The utilization of third party donors; 4) Culture passage number (P); and 5) Source of the cells. This study was designed to determine the superiority of the Platelet Lysates (PL) over FBS on the expansion of MSC, the optimal cell' plating density and days between each pass, and to investigate if donor total nucleated cells (TNC) obtained from the washouts of discharged bags and filters of hematopoietic stem cell transplantation (HSCT) can be expanded to be used at clinical grade. TNC were removed, plated and after the first passage were cultivated in different concentrations with FBS or PL, and the number of days to reach 80% of confluence was observed. Next, cultures with the same plating density were fed either with PL or with FBS and after seven days counted to analyze how much they had grown in that period. The proliferation of mesenchymal stromal cells in the presence of PL and SFB was averaged 11.88 and 2.5 times, respectively, in a period of 7 days. The highest concentration of plating cells using PL took less time to reach confluence as compared with the three lower ones. This study suggests that the PL is the best choice as a supplement to expand MSC and to allow the proliferation of enough number of MSC at P2 for clinical use. KeywordsPlatelet Lysate; MSC, Optimization; Cell Therapy V. Valim et al. 26

No abstract

Mesenchymal stem cells (MSC) are considered non-hematopoietic multipotent stem cells with self-renewal properties and the ability to differentiate into a variety of mesenchymal tissues. Optimal conditions for the culture of these cells have been the subject of investigation for several years. In particular, ideal oxygen tension levels have not been established in the literature. In physiological environments, oxygen tension may vary from 12% in peripheral blood to 1% in the deep zone of cartilage regions. In any case, oxygen tension is considerably lower in vivo when compared with the normal atmosphere of standard cell culture conditions (21%). The objective of this study was to review the literature available on MSC characteristics (cell cycle, survival, proliferation, differentiation, morphology, immunophenotype, cytogenetics) when cultured under hypoxic conditions. Our focus on optimal culture conditions is justified by the key role currently played by these cells in regenerative medicine.

Hematopoietic stem cell transplantation (HSCT) has emerged as a curative strategy for sickle cell anemia (SCA); it is necessary to find markers of SCA clinical severity to spare those SCA patients whose clinical course is mild from the morbidity and mortality associated with HSCT. Haplotypes have been correlated with the severity of clinical manifestations in SCA patients, and fetal hemoglobin (HbF) and socioeconomic status (SeS) have also been described as negative factors. We stu- M. A. L. da Silva et al.17

Background: Damage to the articular cartilage is usually caused by accidental or athletic injuries or trauma often progressing to more severe joint diseases, such as osteoarthritis, subchondral bone necrosis, and arthritis. It is estimated that 15% of the world's adult population is affected by joint diseases. The long-term success of cartilage repair depends on the development of alternative regenerative approaches. In recent years, the use of stem cells for the treatment of degenerative diseases has been widely explored. Here we report a case of exceptional use of autologous bone marrow mesenchymal stem cells expanded in medium supplemented with autologous platelet lysate in a patient with glenoid chondral erosion.Methods: A 17-year-old patient was diagnosed as having chondral erosion of the center of the labrum in the right shoulder, with symptoms of pain and insecurity in the right upper limb. Thirty days before arthroscopy, autologous platelets and stem cells were obtaind from apheresis and BM aspiration, respectively. Arthroscopy was then performed with the patient in the lateral decubitus position with arm abducted to 45° under manual traction. Microfracture was performed in the central region defect, and MSC intra-articular injection was performe after extensive washing with sterile saline. Discussion: No adverse reactions were observed. Two years after arthroscopy, there were no sign of lesion in cartilage, rotator cuff or biceps tendon were observed in magnetic resonance imaging. Further studies are needed to validate the clinical efficacy and safety of MSC injection for glenoid chondral defect treatment. Trial registration:The procedure was approved by Hospital de Clínicas de Porto Alegre Research Ethics Committee -protocol number 14-0545.