Tissue engineering and regenerative medicine -where do we stand?

Raymund E Horch, Ulrich Kneser, Elias Polykandriotis, Volker J Schmidt, Jiaming Sun, Andreas Arkudas, Raymund E Horch, Ulrich Kneser, Elias Polykandriotis, Volker J Schmidt, Jiaming Sun, Andreas Arkudas

Abstract

Tissue Engineering (TE) in the context of Regenerative Medicine (RM) has been hailed for many years as one of the most important topics in medicine in the twenty-first century. While the first clinically relevant TE efforts were mainly concerned with the generation of bioengineered skin substitutes, subsequently TE applications have been continuously extended to a wide variety of tissues and organs. The advent of either embryonic or mesenchymal adult stem-cell technology has fostered many of the efforts to combine this promising tool with TE approaches and has merged the field into the term Regenerative Medicine. As a typical example in translational medicine, the discovery of a new type of cells called Telocytes that have been described in many organs and have been detected by electron microscopy opens another gate to RM. Besides cell-therapy strategies, the application of gene therapy combined with TE has been investigated to generate tissues and organs. The vascularization of constructs plays a crucial role besides the matrix and cell substitutes. Therefore, novel in vivo models of vascularization have evolved allowing axial vascularization with subsequent transplantation of constructs. This article is intended to give an overview over some of the most recent developments and possible applications in RM through the perspective of TE achievements and cellular research. The synthesis of TE with innovative methods of molecular biology and stem-cell technology appears to be very promising.

© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Figures

Fig 1
Fig 1
‘The Fountain of Youth’ is the title of a painting of Lucas Cranach the elder of 1546. The picture represents a bath in which from one side aged women rise in the water which they leave on the other side rejuvenated. Source : Wikipedia[http://de.wikipedia.org/w/index.php?title=Datei:Lucas_Cranach_d._%C3%84._007.jpg&filetimestamp=20050519080127
Fig 2
Fig 2
Micro Ct of TricOS® matrix in an AV-loop within an isolation chamber at 2 weeks after implantation showing sprouting of new microvessels out of the arteriovenous loop.
Fig 3
Fig 3
Corrosion Cast of an axial neovascular assembly, in vivo vascular construct, 2 weeks after vascular induction. Left: Overview of a nascent capillary network. Middle: sprouting angiogenic event. A new capillary sprout emerging from the parent vessel by endothelial pericytic proliferation Right: intussusceptive angiogenic events. The parent vessel is divided into two distinct new vessels for the purpose of vascular growth or remodelling.
Fig 4
Fig 4
HE staining of newly formed bone (*) attached to a HA/TCP matrix (TricOS®, #) 8 weeks after implantation of an arteriovenous loop in the medial thigh of a rat and application of primary osteoblasts and 2.5 + g BMP2. Vascularization of matrices is visible by India Ink-filled vessels (arrows).
Fig 5
Fig 5
Transmission electron microscopy. (A) Human atrial myocardium. A telocyte (digitally coloured in blue) is located among atrial cardiomyocytes (the atrial granules are obvious). Telopodes are situated in between cardiomyocytes (Tp1, Tp2, Tp4, Tp5), and another telopode (Tp3) with close spatial relation with the blood vessels. The apposition of Tp1 and Tp2 suggests that telocytes are realizing a network, by homo-cellular junctions. (B) 1-yr old mouse subepicardial stem-cell niche. Close relationship in between a telocyte and its telopode with a cardiomyocyte progenitor (the cell containing leptofibrills – ‘zebra-like’ striations – Z). The arrow indicates desmosome – the origin for a future intercalated disc. The telocyte have shedding vesicles (asterisks) – digitally coloured in violet. N – nucleus, m – mitochondria Kindly provided by Prof. L.M. Popescu, National Institute of Pathology, Bucharest, Romania.

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