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Systemic sclerosis (SSc) is a rare autoimmune disorder with a high mortality rate. There are still many unknowns concerning the pathophysiology of this disease, due to its clinical heterogeneity. Since there is still no curative treatment, researchers focus on finding novel methods to help the patients. One of the valid options is cellular therapy, and mesenchymal stem cells (MSCs)-based therapy yields great expectations. These cells possess especially valuable attributes regarding key points of SSc. Nevertheless, the effectiveness and safety of this therapy must undergo a rigorous process of veri­fication. In preclinical trials, animal models proved to be a valuable source of scientific knowledge regarding SSc. Because of that, it has been possible to test autologous or allogeneic MSCs from various sources in many clinical trials. A lot of aspects still have to be determined to assess their potential in the management of SSc, probably in association with other therapies.

Liming Wang,1,* Shigao Huang,2,* Shimei Li,1 Ming Li,1 Jun Shi,1 Wen Bai,1 Qianyun Wang,1 Libo Zheng,3 Yongjun Liu3 1Cell Therapy Center, 986 Hospital of People’s Liberation Army Air Force, Xi’an, Shaanxi, People’s Republic of China; 2Cancer Center, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, People’s Republic of China; 3Stem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shigao HuangCancer Center, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Room 3013, Building N-22, Taipa, Macau, People’s Republic of ChinaEmail huangshigao2010@aliyun.comYongjun LiuStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, No. 35, Jinghai 3 Road Economic-Technological Development Area, Beijing, People’s Republic of ChinaEmail andyliuliu2001@aliyun.comBackground: The traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA.Methods: 64 RA patients aged 18–64 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 × 107 cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy.Results: 1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05).Conclusion: UC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.Keywords: rheumatoid arthritis, umbilical cord mesenchymal stem cell, cell therapy

Under the modeling of chronic fibrousing hepatitis in rats (n = 75) the dynamics of fibrolytic effect of bone mar- row MMSC was examined after one or two-time infusion of these cells at the early stage of liver fibrosis. By dynamic measuring of liver fibrotic area and the expression of activated stellate cell markers (desmin, α-SMA) and markers of cell apoptosis (caspase-3 and caspase-9) within 90 days two phases of the development of bone marrow MMSC fibrolytic effect were found. It is shown that the development of fibrolytic effect includes the primary phase of intensification of fibrosis, which is followed by the phase of enhanced fibrolytic process in the liver. It was determined that the two-phase dynamics of liver regeneration was more intensive after two-time infusion of bone marrow MMSC.

BACKGROUND AND OBJECTIVE: The use of an appropriate stimulus to speed up in vitro and in vivo stem cell proliferation and growth is the one of the most important issues in cell therapy. The aim of this study was in vitro evaluation of hydroethanolic extraction of citrus aurantium on proliferation and growth rates of neonate rat neural stem cells. METHODS: Neural stem cells were isolated using enzymatic digestion from hippocampus region of 3 day old neonatal rat brain. To determine optimal concentration of citrus aurantium extraction, isolated neural stem cells were treated at 200, 400, 600, 800 and 1000 µg/ml for 48 h. Then cells proliferation rate were evaluated using MTT assay method. FINDINGS: Citrus aurantium promoted neural stem cells proliferation compared to untreated cells. As well as the effect of aurantium extract is dose dependent. The result of this study showed that proliferative rate in treated cells with 600 µg/ml of Citrus aurantium extraction (0.81±0.06) significantly is higher than control (untreated neural stem cells) group (0.59±0.02). (p

Abstract: The hypothesis is that cell therapy with autologous keratinocytes promotes healing of chronic venous ulcers that failed to respond to other forms of treatment. This is a randomized study in which 31 patients with chronic venous ulcers participated, totaling 38 venous ulcers. Thirty one ulcers were included in Group 1 (G1) treated with autologous keratinocytes applied at the ulcers’ base with autologous fibrin scaffold. Group 2 (G2) included 7 ulcers treated with autologous fibrin glue only. The ulcers were evaluated with digital photography and computer image analysis [area and wound healing rate (WHR)] over 90 days. The duration of ulcers from the G1 was 118 months on average and in G2 the average was 114 months without any difference. In relation to the initial size of ulcers, both groups were similar considering the mean, SD and median respectively: G1 (18; 27; 5.6 cm2) and G2 (19.5; 0.11; 0.29 cm2). The medians of WHR in G1 and G2 have got significant differences between groups. Considering only the wounds that reached WHR larger than 0.4 (40% rate of healing), in the G1, 29% of ulcers reached it at the 30th day, 58% at the 45th, 77% at the 60th, 84% at the 75th and 90% at the 90th day while in the G2 only 14% (one ulcer) reached it at the 30th day remaining steady until the 90th day when only one more ulcer reached this rate (28.6%). The median of procedures was 2 for G1 and 3 for G2. These findings showed the relevant efficacy of cell therapy with autologous keratinocytes applied with autologous fibrin glue scaffold achieving high rates of healing from the thirtieth day of follow-up and becoming larger by the ninetieth day. In contrast, the autologous fibrin glue applied lonely in G2 did not improve the wound healing significantly. The cell therapy with autologous keratinocytes applied with autologous fibrin scaffold promotes greater healing of chronic venous ulcers than autologous fibrin glue only, particularly large recalcitrant ulcers that do not respond to conventional treatment. [Copyright &y& Elsevier]

The limited availability of qualified endothelial progenitor cells (EPCs) is a major challenge for regenerative medicine. In the present study, we isolated human EPCs from human umbilical vein endothelial cells (HUVECs) by using magnetic micro-beads coated with an antibody against human CD34. Flow cytometric assay showed that majority of these cells expressed VEGFR2 (KDR), CD34 and CD133, three molecular markers for early EPCs. It was also found that a bioreactor micro-carrier cell culture system (bio-MCCS) was superior to dish culture for in vitro expansion of EPCs. It expanded more EPCs which were in the early stage, as shown by the expression of characteristic molecular markers and had better angiogenic potential, as shown by matrix-gel based in vitro angiogenesis assay. These results suggest that HUVECs might be a novel promising resource of EPCs for regenerative medicine and that a bio-MCCS cell culture system might be broadly used for in vitro expansion of EPCs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Despite-or perhaps because of-the rapid expansion of interest in stem cell-derived cellular therapy products, relatively few guidelines have been published to assist in the design of scientifically sound preclinical studies. The field is complex and wide ranging, and of necessity regulators tend to treat each project on a case by case basis. One of the core tenets remains the need to retain all tissues from the study, thereby allowing for further analysis of tissues should unexpected effects be seen in clinical studies; attempts to comply with this may result in an unmanageable financial burden. Judicious input from the pathologist at the earliest stages of study design may not only improve the scientific integrity of the study but also help to mitigate some of the cost. Careful animal selection, the development of robust cell markers, and justifiable triage of tissues based on phased tissue examination can all be discussed with the regulatory authorities at pre-pre-investigational new drug (IND) and pre-IND meetings to achieve optimal study design., (© 2014 by The Author(s).)

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development.