Implantable Porous Microtube Cell Reservoir for Sustained Paracrine Therapy of Ischaemic Diseases(1/4)

Project: A - Government Institutionb - Ministry of Science and Technology

Project Details

Description

Ischaemic diseases are the leading cause of mortality in the developed world, including Taiwan. This research will focus on critical limb ischaemia and myocardial infarction. Critical limb ischaemia (CLI) results in severe pain and loss of limb function. Many patients unfortunately require limb amputation, causing permanent disability at great personal, social and economic costs. Myocardial Infarction (MI) results in long-term remodelling of the heart, often leading to cardiac failure when the heart can no longer support the body’s needs of blood circulation. With regard to the two diseases mentioned above, endogenous regeneration of skeletal muscle and cardiac tissue is extremely poor, and there is an urgent need for therapies which can improve outcomes by promoting tissue regeneration over the long-term. Stem cell therapy has great potential as a treatment for ischaemic conditions. However, despite numerous clinical trials over the last decade, only mild to moderate therapeutic benefits have been demonstrated. The greatest limitation is that stem cell survival and retention at the target site is poor, with only a small fraction of injected cells retained for more than 24 hours. Implanted cells secrete extracellular vesicles, soluble growth factors, cytokines, microRNAs and other substances which improve tissue regeneration and encourage recruitment of reparative endogenous cells. However, with poor retention at the target site, these factors are not long-lasting enough to produce large therapeutic benefits. This project aims to utilise an implantable, porous biomaterial sheet containing a reservoir of encapsulated stem cells. Cell encapsulation technology greatly enhances cell viability and retention by reducing the stresses placed on cells during implantation, as well as protecting them from the hypoxic environment and host immune system. At the same time, pores in the encapsulation device allow exchange of nutrients, oxygen and secreted paracrine factors. This novel material has been developed at Taipei Medical University and is in the process of commercialisation. Together with stem cell researchers from the United Kingdom, we aim to encapsulate a newly-discovered population of adult cardiac stem cells. These cells, termed human cardiac mesenchymal-like stem cells (CMSCLCs), have outstanding therapeutic potential due to their extraordinarily high degree of pro-regenerative growth factor secretion. Furthermore, these cells are isolated from surgical waste after coronary bypass, not cadavers, and are therefore a readily accessible, practical cell type for use in cell therapy. This project will be carried out over four years and will result in 1-2 high impact publications. Essential steps include training in CMSCLCs isolation in the UK, in vitro demonstrations of efficacy, characterisation of secreted factors, and murine hind limb ischaemia and murine myocardial infarction models. The study will culminate by demonstrating long-term therapeutic potential on a realistic scale with a porcine limb ischaemia model. This project has clear translational potential and is expected to contribute towards improved health outcomes for patients in Taiwan. Through international collaboration, training of Taiwanese researchers, development of intellectual property, and expected high-impact publications, this project has clear national benefits.
StatusActive
Effective start/end date2/1/201/31/21

Keywords

  • Stem cell therapy
  • ischaemia
  • limb ischaemia
  • myocardial infarction
  • cell encapsulation
  • implantable device
  • paracrine effect
  • extracellular vesicle
  • tissue regeneration
  • regenerative medicine