Fast-Proliferating Adipose Tissue Mesenchymal-Stromal-Like Cells for Therapy

Abstract

Human mesenchymal stromal cells, whether from the bone marrow or adipose tissue (hASCs), are promising cell therapy agents. However, generation of abundant cells for therapy remains to be a challenge, due to the need of lengthy expansion and the risk of accumulating genomic defects during the process. We show that hASCs can be easily induced to a reversible fast-proliferating phenotype (FP-ASCs) that allows rapid generation of a clinically useful quantity of cells in < 2 weeks of culture. Expanded FP-ASCs retain their finite expansion capacity and pluripotent properties. Despite the high proliferation rate, FP-ASCs show genomic stability by array-comparative genomic hybridization, and did not generate tumors when implanted for a long time in an SCID mouse model. Comparative analysis of gene expression patterns revealed a set of genes that can be used to characterize FP-ASCs and distinguish them from hASCs. As potential candidate therapeutic agents, FP-ASCs displayed high vasculogenic capacity in Matrigel assays. Moreover, application of hASCs and FP-ASCs in a fibrin scaffold over a myocardium infarct model in SCID mice showed that both cell types can differentiate to endothelial and myocardium lineages, although FP-ASCs were more potent angiogenesis inducers than hASCs, at promoting myocardium revascularization.

Glioblastoma Bystander Cell Therapy: Improvements in Treatment and Insights into the Therapy Mechanisms

“…TK-expressing FP-hAMSCs were as effective as TK-hAMSCs at inhibiting GB growth, and multiple applications of therapeutic cells prolonged MS of animals, inducing a chronic disease state. Considering our previous observation of FP-hAMSCs phenotype reversibility, 28 it is tempting to speculate that following brain implantation, FP-hAMSCs revert to the hAMSCs phenotype and exert similar anti-tumor effects.…”

“…The requirement of a large number of genetically modified therapeutic cells for GB therapy could be met by growth of hAMSCs in endothelial cell growth medium 2 (EGM2), a medium that induces a fast proliferating phenotype (FP-hAMSCs). 28 To test the therapeutic capacity of FP-hAMSCs, hAMSCs were made luminescent, fluorescent, and cytotoxic by transduction with a tri-functional CMV:hRluc:mRFP:tTK lentiviral vector (Rluc-RFP-TK-hAMSCs), and positively transduced RFP cells were sorted by fluorescence-activated cell sorter (FACS). Fast proliferating cells (Rluc-RFP-TK-FP-hAMSCs) were obtained by cultivating Rluc-RFP-TK-hAMSCs in EGM2 medium.…”

Directional Topography Influences Adipose Mesenchymal Stromal Cell Plasticity: Prospects for Tissue Engineering and Fibrosis

“…One particular type of MSC is the adipose tissue-derived stromal cell (ASC). In addition to the characteristics common to MSC, ASC have a number of advantages as a source of precursor cells for the production of TEBV: they are easy to acquire, culture, propagate, and differentiate [8–12].…”

Wharton’s Jelly Mesenchymal Stromal Cells and Derived Extracellular Vesicles as Post-Myocardial Infarction Therapeutic Toolkit: An Experienced View

“…Collectively, the presented evidence-based pre-clinical experience using MSC and cardiac ECM supports the achievement of beneficial effects on cardiac function following MI [ 59 , 60 , 61 , 62 , 63 ]. This was shown to be crucial for the regulatory approval of a novel advanced therapeutic medicinal product (ATMP) termed PeriCord by the Spanish Agency of Medicines and Medical Devices (AEMPS) (PEI18-140).…”