Research Work Combining Vector and Stem cells for Treatment of Ischemia – TRAVESTI

The vascular network is a fundamental component for an organ because it allows the delivery of all molecules necessary for its metabolism (nutrients, respiratory gases, growth factors and endocrine, etc.) and thereby under-perfusion leads to many chronic diseases. For some, ischemia is directly the etiological cause of cellular degeneration such as arterial disease during exposure to chronic hyperglycaemia. For others, the etiology of cell degeneration is not fully understood but the decrease of the vascular network is a key element in the evolution of the disease (degeneration of the urethral sphincter in urinary incontinence or the arterial system in veno-occlusive erectile dysfunction, graft rejection in kidney transplant). All of these diseases represents a major impact, by the absence of etiologic treatment, on costs of health and well-being of patients. One hopes for a cure of these diseases is ischemic cell therapy. Recently, in order to abstract the major difficulties of ethical and technical issues related to the use of embryonic pluripotent stem cells, therapeutic strategies have been explored with non-embryonic stem cells (MSC adult mesenchymal stem cells). The two main sources are bone marrow and adipose tissue. In both tissues, there are MSC with potential angiogenic and it is shown that stem cells derived from adipose tissue (ADSC) give better results in terms of neo-vascularization. The vast majority of studies using MSC is performed after in vitro culture of progenitor cells. Cell culture is a very demanding stage for the regulatory instances, requires very expensive infrastructure, and is also a technique in which iatrogenic risks are not yet evaluated. It has been clearly shown that the action of ADSC passes overwhelmingly by the paracrine secretion of pro-angiogenic factors for the recruitment and activation of cells already present in ischemic tissue. Neovascularization is linked to the secretory power of pro-angiogenic factors rather than direct participation of the number of cells injected. Thus, the amplification step of the culture may not be a required step. In this project we develop a strategy of using autologous ADSC for an extemporaneous injection, on several experimental animal models (mouse, rat, pig), mimicking the major diseases related to ischemia (diabetic members, urinary incontinence, erectile dysfunction , kidney transplant). To optimize this strategy we want to use PAMs (biodegradable polymeric spheres) for the attachment of ADSCs on a biomimetic matrix (formed from elements of the extracellular matrix). The TRAVESTI research program will allow to test the therapeutic efficacy of this new vectorial association in various pathologies associated with ischemia. Indeed, the association ADSC + WFP increase significantly the survival of cells injected and, therefore, very probably, their therapeutic power. To strengthen the latter, the second advantage of PAMs is the possibility to choose the type of biomimetic matrix that will lead to better stimulate the secretion of pro-angiogenic factors. Three different matrices will be tested in the project. According to the results obtained, we think we can drop one or more patents on innovative therapeutic tools (purification and packaging of ADSC) for the treatment of diseases having a major impact on quality of life of patients and the public health expenditure.