Tissue Development, Regeneration and Repair

Group leader: 
Bruno Péault
Position: 
Professor of Vascular Regeneration
Contact: 

bruno [dot] peault [at] ed [dot] ac [dot] uk or lorraine [dot] vaughan [at] ed [dot] ac [dot] uk (PA)

Members: 
Ania Stefanska (PhD Student)
Christopher West (Clinical PhD Student)
Emanuele Azzoni (Post Doc)
Iain Murray (Clinical PhD Student)
James Bailey (Clinical PhD Student)
Li-Jun Ding (Post Doc)
Nick Arkoulis (Clinical Research Fellow)
Nusrat Khan (Senior Post Doc)
Paul Hindle (PhD Student)
Zaniah Gonzalez Galofre (PhD Student)

Aim
Working closely with the Edinburgh / BHF Centre for Cardiovascular Science and our twin laboratory at the University of California in Los Angeles, we study the biology of perivascular stem cells and their possible role in tissue development, renewal and repair.

Background
Embryonic stem cells – which can generate all tissues and organs – build up the embryo but become progressively restricted in their potency, so that only specialized, tissue restricted stem cells are present in the adult to regenerate blood, muscle, skin and other tissues.

However, multipotent stem cells have also been identified in adult tissues. For instance, mesenchymal stem cells (MSC) can renew bone, cartilage, fat and muscle. MSC are present in all organs, therefore can be conveniently harvested from tissues which are released during normal life (milk teeth, placenta…) or are dispensable (fat).

For all these reasons, MSC have become popular candidates for stem cell therapies. In addition, MSC have unique properties; for instance they can control adverse effects of the immune system, like rejection of transplanted tissues, and auto-immune diseases. MSC have been known for about four decades; however these stem cells were extracted only indirectly from tissues which had been dissociated into single cells and cultured over the long term. Consequently, the native identity and localization of MSC remained unknown.


Image shows human MSC in culture.

Over the past few years, our laboratory has attempted to identify and purify MSC and discovered that original MSC are located at the periphery of blood vessels. This explains why MSC had been previously isolated from all organs, since all organs contain blood vessels. These ancestral MSC are named pericytes or adventitial cells, and are located around small and large vessels respectively.
 

Image shows a cross-section through a human placental villus, showing blood vessels of different calibers. Endothelial cells (green) are ensheathed by pericytes (red).

Our work will contribute to a better understanding of how novel perivascular stem cells contribute to tissue development and repair. In addition, using these purified stem cells instead of the conventional heterogenous MSC may offer siginificant opportunities to improve stem cell therapies.

Approach and progress
The activity of our research group, established at the MRC Centre for Regenerative Medicine in 2010, is two-fold. Several projects address the basic biology of perivascular cells (pericytes and adventitial cells). We are investigating the molecular and anatomic identification in man and animals  like mice, rats, dogs, sheep, and fish. We are also looking at the ontogeny, developmental potential, immunomodulatory activity, ability to sustain hematopoietic stem cells (role in the constitution of the blood stem cell "niche"), and communication with adjacent cells – like endothelial cells – and role of the latter in regulating these potentials in vivo.

In parallel, our group is investigating the therapeutic potential of these cells in medical conditions, currently focusing principally on cardiac repair, cartilage regeneration and bone healing. This project is supported by an important Early Translational Grant of the California Institute for Regenerative Medicine (2011-2014) and currently represents the major collaboration between UCLA and the University of Edinburgh.


Image shows skeletal myofibers (red) regenerated by human fat derived stem cells.

Prof Péault has long been involved in the developmental biology of hematopoiesis. He was the first to identify and characterize the embryonic origin of human definitive hematopoietic stem cells, which are responsible for blood cell production. Our group continues to pursue these studies both in normal development and in the model of embryonic stem cells (ES cells). We have recently identified a novel marker for the ancestral hemangioblast, the common stem cell for hematopoietic cells and endothelial cells.

Selected publications

  • Sinka L, Biasch K, Khazaal I, Péault B, Tavian M. 2012. Angiotensin-converting enzyme (CD143) specifies emerging lympho-hematopoietic progenitors in the human embryo. Blood. In press.
  • Peault B. 2012. Are Mural Cells Guardians of Stemness? From pluri- to multipotency via vascular pericytes. Circulation 125:12-13. Editorial, doi: 10.1161/CIRCULATIONAHA.111.073445.
  • Corselli M, Chen CW, Sun B, Yap S, Rubin P, Péault B. 2011. The tunica adventitia of human arteries and veins as a source of mesenchymal stem cells. Stem Cells and Development. In press. doi: 10.1089/scd.2011.0200.
  • Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Yap S, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Bühring HJ, Giacobino JP, Lazzari L, Huard J, Péault B. 2008. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301-313. doi: 10.1016/j.stem.2008.07.003.
  • Zambidis ET, Park TS, Yu W, Tam A, Levine M, Yuan X, Pryzhkova M, Péault B. 2008. Expression of ACE identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells. Blood 112:3601-3614. doi: 10.1182/blood-2008-03-144766.
  • Zheng B, Cao B, Crisan M, Sun B, Li G, Logar A, Yap S, Pollett JB, Drowley L, Cassino T, Gharaibeh B, Deasy BM, Huard J, Péault B. 2007. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nature Biotechnology 25(9):1025-1034. doi:10.1038/nbt1334

Funding

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Peault publications 2007-201177.79 KB