Module 7: Primitive iPS-derived MSC for Bone Repair

 Module Leader Professor Nick Fisk
 Host Organisation UQ Centre for Clinical Research, University of Queensland

Module description

Clinical development of iPS cells is focused on tissue engineering rather than cell therapy, because like hESCs, iPS are tumourogenic. In contrast mesenchymal stem cells (MSC) do not form tumours, can be given systemically, and are under intense investigation as cell therapy for cardiac, muscle, endothelial, spinal, brain, bone, cartilage and graft versus host indications. Adult MSC are limited by their rarity, lineage restriction and variable immunomodulation, in contrast to early fetal MSC, which show more primitive growth kinetics, multilineage differentiation, telomerase, embryonic marker expression, and immunonaivete, but are ethically or technically challenging to isolate for allogeneic or autologous use.

A number of groups have now derived MSC from ES cells, and recent attempts using virus, serum and feeder free methods show that hES-derived MSC show more primitive gene expression and immunomodulatory profiles, suggestive of more fetal-like properties.

Aims

  1. To derive fetal-like MSC from iPS.
  2. To demonstrate iPS-derived MSC repair bone in vivo.

Module Leader biography

Nick Fisk is the inaugural Director of the University of Queensland’s new state of the art $66M Centre for Clinical Research on the Herston campus, and a maternal-fetal medicine specialist / high risk obstetrician at the Royal Brisbane and Women’s Hospital.

Between 1992-2007 he was Professor of Obstetrics /Fetal Medicine at Imperial College & Queen Charlotte’s/Hammersmith Hospitals in London, where his laboratory and clinical research program achieved an international reputation in fetal diagnosis and treatment. His main research interests have focussed on human fetal mesenchymal stem cell biology and monochorionic multiple pregnancy. His group first characterised primitive mesenchymal stem cells in the fetal circulation, and showed how they cross into the mother to engraft lifelong in maternal organs. In more recent work, fetal MSC transplantation is being developed to repair genetic disease such as osteogenesis imperfecta in utero. A clinical scientist with an MBA and a PhD in fetal physiology, he is a past President of the International Fetal Medicine and Surgery Society, and has authored over 300 publications, and. He reviews for numerous international grant bodies, and is a member of several editorial boards including PLoS Medicine.

Contact details

 E-mail  n.fisk@uq.edu.au
 Phone   +61 7 3346 5500
 Web  www.uqccr.uq.edu.au

Selected publications

  1. Campagnoli C, Roberts IAG, Kumar S, Bennett PR, Bellantuono I, Fisk NM: Identification of mesenchymal stem/progenitor cells in human first trimester fetal blood, liver and bone marrow. Blood 98: 2396-402, 2001.
  2. O’Donoghue K, Chan J, de la Fuente J, Kennea N, Sandison A, Anderson JR, Roberts IAG, Fisk NM: Micro-chimerism in female bone marrow and bone decades after fetal mesenchymal stem cell trafficking in pregnancy. Lancet 364: 179-82, 2004.
  3. Chan J, O’Donoghue K, de la Fuente J, Roberts IA, Kumar S, Morgan JE, Fisk NM: Human fetal mesenchymal stem cells as vehicles for gene delivery. Stem Cells 23: 93-102, 2005.
  4. Chan J, O’Donoghue K, Gavina M, Torrente Y, Kennea N, Mehmet H, Stewart H, Watt D, Morgan JE, Fisk NM: Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration. Stem Cells 24: 1879-91, 2006.
  5. Guillot PV, Gotherstrom CA, Chan J, Kurata H, Fisk NM: Human first trimester fetal mesenchymal stem cells (MSC) express pluripotency markers, grow faster, and have longer telomeres compared to adult MSC. Stem Cells 25: 646-54, 2007.
  6. Bianchi D, Fisk NM: Gender matters: fetomaternal cell trafficking and the stem cell debate. JAMA 297: 1489-91, 2007.
  7. Chan J, Waddington SN, O’Donoghue K, Kurata H, Guillot PV, Gotherstrom C, Themis M, Morgan JE, Fisk NM:  Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse.  Stem Cells 25: 875-84, 2007.
  8. Guillot PV, De Bari C, Dell’Accio F, Kurata H, Polak J, Fisk NM: Comparative osteogenic transcription profiling of various fetal and adult mesenchymal stem cell sources. Differentiation 76:946-57, 2008.
  9. Santos MA, O’Donoghue K, Wyatt-Ashmead J, Fisk NM: Fetal cells in the maternal appendix: a marker of inflammation or fetal tissue repair? Hum Reprod 23:2319-25, 2008.
  10. Guillot PV, Abass O, Bassett JH, Shefelbine SJ, Bou-Gharios G, Chan J, Kurata H, Williams GR, Polak J, Fisk NM: Intrauterine transplantation of human fetal mesenchymal stem cells from first trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood 111:1717-1725, 2008.