PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages.
We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs ... More
Ischemic Preconditioning Potentiates the Protective Effect of Stem Cells through Secretion of Exosomes by Targeting Mecp2 via miR-22.
AuthorsFeng Y, Huang W, Wani M, Yu X, Ashraf M,
Journal
PubMed ID24558412
Mesenchymal stem cells (MSCs) have potential application for the treatment of ischemic heart diseases. Besides differentiation properties, MSCs protect ischemic cardiomyocytes by secretion of paracrine factors. In this study, we found exosomes enriched with miR-22 were secreted by MSCs following ischemic preconditioning (Exo(IPC)) and mobilized to cardiomyocytes where they reduced ... More
Critical steps in the isolation and expansion of adipose-derived stem cells for translational therapy.
Since the discovery of adipose-derived stem cells (ASCs), there have been high expectations of their putative clinical use. Recent advances support these expectations, and it is expected that the transition from pre-clinical and clinical studies to implementation as a standard treatment modality is imminent. However ASCs must be isolated and ... More
Serum-free, xeno-free culture media maintain the proliferation rate and multipotentiality of adipose stem cells in vitro.
BACKGROUND AIMS: Human adipose stem cells (ASC) are an abundant, readily available population of multipotent progenitor cells that reside in adipose tissue. ASC have been shown to have therapeutic applicability in pre-clinical studies, but a standardized expansion method for clinical cell therapy has yet to be established. Isolated ASC are ... More
Growth, differentiation capacity, and function of mesenchymal stem cells expanded in serum-free medium developed via combinatorial screening.
AuthorsCrapnell K, Blaesius R, Hastings A, Lennon DP, Caplan AI, Bruder SP
JournalExp Cell Res
PubMed ID23597555
The presence of serum in cell culture medium presents an obstacle to safe and efficient production of hMSCs for therapeutic purposes. Availability of defined medium will be crucial to elucidating the mechanism of action of hMSCs in many indications as well as a prerequisite to consistently produce cells with predictable ... More
Human mesenchymal stem cells from the umbilical cord matrix: successful isolation and ex vivo expansion using serum-/xeno-free culture media.
AuthorsSimões IN, Boura JS, dos Santos F, Andrade PZ, Cardoso CM, Gimble JM, da Silva CL, Cabral JM
JournalBiotechnol J
PubMed ID23420807
Mesenchymal stem cells (MSC) could potentially be applied in therapeutic settings due to their multilineage differentiation ability, immunomodulatory properties, as well as their trophic activity. The umbilical cord matrix (UCM) represents a promising source of MSC for biomedical applications. The number of cells isloated per umbilical cord (UC) unit is ... More
Toward a clinical-grade expansion of mesenchymal stem cells from human sources: a microcarrier-based culture system under xeno-free conditions.
AuthorsSantos Fd, Andrade PZ, Abecasis MM, Gimble JM, Chase LG, Campbell AM, Boucher S, Vemuri MC, Silva CL, Cabral JM
JournalTissue Eng Part C Methods
PubMed ID21895491
The immunomodulatory properties of mesenchymal stem cells (MSCs) make them attractive therapeutic agents for a wide range of diseases. However, the highly demanding cell doses used in MSC clinical trials (up to millions of cells/kg patient) currently require labor intensive methods and incur high reagent costs. Moreover, the use of ... More
A xenogeneic-free bioreactor system for the clinical-scale expansion of human mesenchymal stem/stromal cells.
AuthorsDos Santos F, Campbell A, Fernandes-Platzgummer A, Andrade PZ, Gimble JM, Wen Y, Boucher S, Vemuri MC, da Silva CL, Cabral JM
Journal
PubMed ID24420557
The large cell doses (>1?×?10(6) ?cells/kg) used in clinical trials with mesenchymal stem/stromal cells (MSC) will require an efficient production process. Moreover, monitoring and control of MSC ex-vivo expansion is critical to provide a safe and reliable cell product. Bioprocess engineering approaches, such as bioreactor technology, offer the adequate tools ... More
LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
AuthorsHeo SK, Noh EK, Gwon GD, Kim JY, Jo JC, Choi Y, Koh S, Baek JH, Min YJ, Kim H
JournalPLoS One
PubMed ID27835685
LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T ... More
Evaluation of GMP-compliant culture media for in vitro expansion of human bone marrow mesenchymal stromal cells.
AuthorsWuchter P, Vetter M, Saffrich R, Diehlmann A, Bieback K, Ho AD, Horn P
JournalExp Hematol
PubMed ID26911671
Mesenchymal stromal cells (MSCs) from human bone marrow serve as a resource for cell-based therapies in regenerative medicine. Clinical applications require standardized protocols according to good manufacturing practice (GMP) guidelines. Donor variability as well as the intrinsic heterogeneity of MSC populations must be taken into consideration. The composition of the ... More
Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells.
AuthorsSwioklo S, Constantinescu A, Connon CJ,
JournalStem Cells Transl Med
PubMed ID26826163
: Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4°C-23°C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium ... More
Targeting YAP in malignant pleural mesothelioma.
AuthorsZhang WQ, Dai YY, Hsu PC, Wang H, Cheng L, Yang YL, Wang YC, Xu ZD, Liu S, Chan G, Hu B, Li H, Jablons DM, You L
JournalJ Cell Mol Med
PubMed ID28470935
Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes-associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. First, we comprehensively studied YAP activity in five mesothelioma cell lines (211H, ... More
DCLK1 is correlated with MET and ERK5 expression, and associated with prognosis in malignant pleural mesothelioma.
AuthorsWang H, Dai YY, Zhang WQ, Hsu PC, Yang YL, Wang YC, Chan G, Au A, Xu ZD, Jiang SJ, Wang W, Jablons DM, You L
JournalInt J Oncol
PubMed ID28560410
Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P<0.05). We ... More