Development of pluripotent stem cells for vascular therapy

Abstract

Peripheral arterial disease (PAD) is characterized by reduced limb blood flow due to arterial obstruction. Current treatment includes surgical or endovascular procedures, the failure of which may result in amputation of the affected limb. An emerging therapeutic approach is cell therapy to enhance angiogenesis and tissue survival. Small clinical trials of adult progenitor cell therapies have generated promising results, although large randomized clinical trials using well-defined cells have not been performed. Intriguing pre-clinical studies have been performed using vascular cells derived from human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPSCs). In particular, hiPSC-derived vascular cells may be a superior approach for vascular regeneration. The regulatory roadmap to the clinic will be arduous, but achievable with further understanding of the reprogramming and differentiation processes; with meticulous attention to quality control; and perseverance.

A Compendium on Peripheral Arterial Disease

“…Subsequently, the iPSCs can be differentiated into cells that are less easily obtained from the patient, such as endothelial cells (16). These iPSC-derived cells permit the study of “disease-in-a-dish” and are accelerating our discovery of new pathobiological insights and therapeutic approaches (17). …”

Induced Pluripotent Stem Cell-Derived Endothelial Cells Overexpressing Interleukin-8 Receptors A/B and/or C-C Chemokine Receptors 2/5 Inhibit Vascular Injury Response

“…Use of iPS cells can eventually enable the development of autologous cell therapy and thus overcome the major hurdle that stands in the way of practical application of cell therapy for human diseases. The successful use of rat iPS derived into ECs in preventing the inflammation and adverse vascular remodeling that results from acute vascular injury provides proof of concept in support of potential therapeutic interventions using autologous cell therapy, as described by Volz et al [24]. A major concern of using cell therapy as a potential treatment for human diseases is rejection of the transplanted cells; autologous cell therapy overcomes the obstacle of rejection [24].…”

Generating induced pluripotent stem cell derived endothelial cells and induced endothelial cells for cardiovascular disease modelling and therapeutic angiogenesis

“…Multipotent cells have decreased capacity for self-renewal compared to pluripotent cells and can only form a limited number of different cell types. Previous reviews have highlighted the advantages and limitations of each of the three major stem cell types as potential cardiovascular regenerative therapies [30][31][32].…”