Yael Porat

Isolation of an adult blood‐derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages

Blood‐derived adult stem cells were previously considered impractical for therapeutic use because of their small numbers. This report describes the isolation of a novel human cell population derived from the peripheral blood, termed synergetic cell population (SCP), and defined by the expression of CD31Bright, CD34+, CD45−/Dim and CD34Bright, but not lineage‐specific features. The SCP was capable of differentiating into a variety of cell lineages upon exposure to defined culture conditions. The resulting cells exhibited morphological, immunocytochemical and functional characteristics of angiogenic, neural or myocardial lineages. Angiogenic cell precursors (ACPs) expressed CD34, CD133, KDR, Tie‐2, CD144, von Willebrand factor, CD31Bright, concomitant binding of Ulex‐Lectin and uptake of acetylated low density lipoprotein (Ac‐LDL), secreted interleukin‐8, vascular endothelial growth factor and angiogenin and formed tube‐like structures in vitro. The majority of CD31Bright ACP cells demonstrated Ac‐LDL uptake. Neural cell precursors (NCPs) expressed the neuronal markers Nestin, βIII‐Tubulin, and Neu‐N, the glial markers GFAP and O4, and responded to neurotransmitter stimulation. Myocardial cell precursors (MCPs) expressed Desmin, cardiac Troponin and Connexin 43. In conclusion, the simple and rapid method of SCP generation and the resulting considerable quantities of lineage‐specific precursor cells makes it a potential source of autologous treatment for a variety of diseases.

Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes.

We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro.

A novel potential therapy for vascular diseases: blood-derived stem/progenitor cells specifically activated by dendritic cells

Vascular diseases are a major cause of morbidity and mortality, particularly in diabetic patients. Stem/progenitor cell treatments with bone marrow‐derived cells show safety and promising outcomes, albeit not without some preprocedural adverse events related to cell collection and mobilization. We describe a novel technology for generating a therapeutic population (BGC101) of enriched endothelial progenitor cells (EPCs) from non‐mobilized blood, using dendritic cells to specifically direct stem/progenitor cell activity in vitro.

Critical elements in the development of cell therapy potency assays for ischemic conditions

A successful potency assay for a cell therapy product (CTP) used in the treatment of ischemic conditions should quantitatively measure relevant biological properties that predict therapeutic activity. This is especially challenging because of numerous degrees of complexity stemming from factors that include a multifactorial complex mechanism of action, cell source, inherent cell characteristics, culture method, administration mode and the in vivo conditions to which the cells are exposed. The expected biological function of a CTP encompasses complex interactions that range from a biochemical, metabolic or immunological activity to structural replacement of damaged tissue or organ. Therefore, the requirements for full characterization of the active substance with respect to biological function could be taxing. Moreover, the specific mechanism of action is often difficult to pinpoint to a specific molecular entity; rather, it is more dependent on the functionality of the cellular components acting in a in a multifactorial fashion. In the case of ischemic conditions, the cell therapy mechanism of action can vary from angiogenesis, vasculogenesis and arteriogenesis that may activate different pathways and clinical outcomes. The CTP cellular attributes with relation to the suggested mechanism of action can be used for the development of quantitative and reproducible analytical potency assays. CTPs selected and released on the basis of such potency assays should have the highest probability of providing meaningful clinical benefit for patients. This White Paper will discuss and give examples for key elements in the development of a potency assay for treatment of ischemic disorders treated by the use of CTPs.

Cell Therapy for Vascular Diseases in Israel

In Israel, as elsewhere in the world, people with vascular disease suffer severe complications, including critical limb ischemia, which can result in gangrene and amputation. This chapter describes the step-wise progression in translational medical research as a scientific breakthrough progresses from a laboratory invention to the start of a clinical trial. The novel idea is a method whereby a sub-population of non-mobilized peripheral blood cells can be turned, within a day, into a cellular therapeutic product code-named BGC101, composed of endothelial progenitor cells (EPCs) and Stem/progenitor cell (SPCs). In addition, the benefits of collaboration between an Israeli biotechnology company and an Israeli medical center in overcoming the hurdles of bringing the idea to fruition will be described.