**7. Role of stem cells in regenerative medicine**

The potency of multilineage differentiation and self-renewal makes stem cells an attractive target for scientific approaches concerning tissue repair and regeneration. The interesting cell populations in this context are embryonic and mesenchymal stem cells.

#### **7.1. Embryonic stem cells**

Human embryonic stem cells are capable of self-renewal and differentiation in cells from all germ layers. These regenerative characteristics are very attractive in basic science as well as in potential clinical applications. The pros and cons of embryonic stem cell therapy are discussed controversially.

Current investigations describe the cells potential to differentiate into vascular cell lines and therefore to support tissue repair via angiogenesis. The difficulty is to control and regulate the cell proliferation and differentiation to avoid spontaneous development of teratoma from undifferentiated embryonic stem cells.

In figure 4 an overview of different culture protocols to induce vascular differentiation from embryonic stem cells is given (Descamps, Emanueli et al., 2012).

**Figure 4.** Vascular differentiations

**6.3. Critical aspects**

466 Regenerative Medicine and Tissue Engineering

endothelial function (Sun, Bai et al., 2009).

an insufficiency in the cell-cell junctions (Zisch, Lutolf 2003).

have to be refined (Barralet, Gbureck et al., 2009).

**7.1. Embryonic stem cells**

controversially.

**7. Role of stem cells in regenerative medicine**

populations in this context are embryonic and mesenchymal stem cells.

Many promising investigations featuring growth factor therapy are performed in cell culture or healthy young animals. The therapeutic use of these developments especially addresses the ageing population suffering from ischemic diseases and vascular degeneration. Special attention in coming investigations has to be shifted to the functionality and regenerative demands of diseased of damages cells and tissues. Therapeutic angiogenic strategies have to be scrutinized under the focus of safety and effectiveness in systems with impaires endogenous

Beside the form of application, the definition of the ideal dose of angiogenic growth factor is one the most difficult questions to answer. When dealing with loaded scaffolds one has to define release kinetics. Additionally, in histological investigations, the vasculature that develops under the influence of high doses of VEGF repeatedly showed malformations and

In most therapeutic concepts the desired effect of VEGF is a local one and aims to improve the formation of nutritive vasculature supporting tissue regeneration in a limited area of tissue as well as a in a limited period of time. VEGF application has to take place locally and only during defined period; considering the fact, the VEGF coming with increased angiogenesis is part of many pathologic processes, e.g. tumour vascularisation or proliferative retinopathy, the control of VEGF effect has to be granted. These demands require a lot of conceptional research considering the therapeutic application of VEGF. The angiogenic and osteogenic effects of VEGF delivered from poly-lactide scaffolds in irradiated osseous defects was illustrated impressively in increased vascularisation and bone formation, the application of a potent growth factor in tumour patients however bears many risks (Kaigler, Wang et al., 2006)

In every therapeutic concept the medical gain and the patients´ profit has to be weighed against the impending costs. Nowadays the production of recombinant VEGF in the desired doses is enormous. For routine clinical application the methods of generation, application and delivery

The potency of multilineage differentiation and self-renewal makes stem cells an attractive target for scientific approaches concerning tissue repair and regeneration. The interesting cell

Human embryonic stem cells are capable of self-renewal and differentiation in cells from all germ layers. These regenerative characteristics are very attractive in basic science as well as in potential clinical applications. The pros and cons of embryonic stem cell therapy are discussed Therapeutic neo-vascularisation is of extraordinary interest in the therapy of cerebral or heart ischemia and regenerative strategies. In mouse models with limb ischemia the implantation of embryonic stem cells – alone or in combination with muscle cells – proved a significantly better perfusion via neo-vascularisation in stark contrast to an implantation of adult endothe‐ lial cells (Kane, Xiao et al., 2010).

The positive results in animal models are promising. Yet the pitfalls of stem cell transfer represented by tumorigenicity and immunocompatibility have to be overcome (Descamps, Emanueli et al., 2012).

#### **7.2. Mesenchymal stem cells**

In contrast to embryonic stem cells, mesenchymal stem cells are characterized by pluripotency. These adult stem or progenitor cells, harvested from fat, skin or dental pulp are less prone to ethical concerns and directly available for autologous approaches.

Especially in cardiovascular regeneration mesenchymal stem cells hold great promise for further advanced in therapeutic strategies.

In different investigations these cell lines have shown their potential: not only are they able to differentiate into vascular cells, endothelial cells or pericytes, in addition they stimulate the local cells via paracrine secretion of growth and transcription factors, among others VEGF or IGF. In this context, a secretion of microparticles by the pluripotent cells has been observed; these particles seem to support the regenerative process, the mechanism behind this phenom‐ enon is not understood (Vono, Spinetti et al., 2012).
