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Activin-Directed Differentiation of Human Embryonic Stem Cells Differentially Modulates Alveolar Epithelial Wound repair via Paracrine Mechanism

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Stem Cell Discovery 2014年第3期4卷 67-82页

作者： Khondoker M. Akram Monica A. Spiteri nicholas r. forsyth Institute for Science and Technology in Medicine School of Postgraduate Medicine Keele University Stoke-on-Trent UK

Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. rT-PCr and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.

关键词： Embryonic Stem Cells Alveolar Epithelial Wound repair Idiopathic Pulmonary Fibrosis (IPF) Embryonic Stem Cell-Mediated Paracrine Mechanism Activin-Directed hESC Differentiation

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Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) supports adhesion and migration of mesenchymal stem cells and tenocytes

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World Journal of Stem Cells 2012年第9期4卷 94-100页

作者： Alex J Lomas George GQ Chen Alicia J El Haj nicholas r forsyth Guy Hilton research Centre Keele University Stoke on Trent ST4 7QB United Kingdom Department Biological Sciences and Biotechnology School of Life Science Tsinghua University

AIM: To establish the potential of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) as a material for tendon repair. METHODS: The biocompatibility of PHBHHx with both rat tenocytes (rT) and human mesenchymal stem cells (hMSC) was explored by monitoring adhesive characteristics on films of varying weight/volume ratios coupled to a culture atmosphere of either 21% O2 (air) or 2% O2 (physiological normoxia). The diameter and stiffness of PHBHHx films was established using optical coherence tomography and mechanical testing, respectively. rESULTS: Film thickness correlated directly with weight/volume PHBHHx (r2 = 0.9473) ranging from 0.1 mm (0.8% weight/volume) to 0.19 mm (2.4% weight/volume). Film stiffness on the other hand displayed a biphasic response which increased rapidly at values > 1.6% weight/volume. Optimal cell attachment of rT required films of ≥ 1.6% and ≥ 2.0% weight/volume PHBHHx in 2% O2 and 21% O2 respectively. A qualitative adhesion increase was noted for hMSC in films ≥ 1.2% weight/volume, becoming significant at 2% weight/volume in 2% O2. An increase in cell adhesion was also noted with ≥ 2% weight/volume PHBHHx in 21% O2. Cell migration into films was not observed. CONCLUSION: This evaluation demonstrates that PHBHHx is a suitable polymer for future cell/polymer replacement strategies in tendon repair.

关键词： Mesenchymal stem cell Tenocytes Polyhydroxyalkanoates Hypoxia Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)

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Stem cell-based therapy for human diseases

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3242-3282页

作者： Duc M.Hoang Phuong T.Pham Trung Q.Bach Anh T.L.Ngo Quyen T.Nguyen Trang T.K.Phan Giang H.Nguyen Phuong T.T.Le Van T.Hoang nicholas r.forsyth Michael Heke Liem Thanh Nguyen Department of research and Development Vinmec Research Institute of Stem Cell and Gene TechnologyVinmec Healthcare SystemHanoiVietnam Department of Cellular Therapy Vinmec High.Tech CenterVinmec Healthcare SsystemHanoiVietnam Institute for Science&Technology in Medicine Keele UniversityKeeleUK a Department of Biology Stanford UniversityStanfordCAUSA

recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be *** cell-based therapy,including human pluripotent stem cells(hPsCs)and multipotent mesenchymal stem cells(MSCs),has recently emerged as a key player in regenerative *** are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body,including three germ *** are multipotent progenitor cells possessing self-renewal ability(limited in vitro)and differentiation potential into mesenchymal lineages,according to the International Society for Cell and Gene Therapy(ISCT).This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow(BM),adipose tissue(AT),or the umbilical cord(UC)for the treatment of human diseases,including neurological disorders,pulmonary dysfunctions,metabolic/endocrine-related diseases,reproductive disorders,skin burns,and cardiovascular ***,we discuss our own clinical trial experiences on targeted therapies using MsCs in a clinical setting,and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications,with the ultimate objective of facilitating translational research in regenerative medicine into clinical *** mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment,AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration,and UC-MsCs are potentially good candidates for pulmonary disease and acute respiratory distress svndrometreatment.

关键词： diseases distress treatment

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