Centre for Reproduction & Development

Reprogramming of somatic cells

Lab head: Dr Paul Verma

Pluripotent embryonic stem cells (ESCs) could potentially generate specific cell types for understating and treating degenerative diseases. The cells also have potential for application in livestock development and species conservation, however access to embryos raises a number of ethical, scientific and logistical issues. Recently it has been shown that introduction of a few embryonic genes, can ‘reprogram’ adult cells into embryonic stem cell equivalents, know as induced pluripotent stem cells (iPSCs).

Our lab was the first to develop iPSCs in Australia from mice^1,2, humans³ and patients with disease⁴. We are also exploring application of this exciting approach for benefit to the livestock industry^5,6 and for species conservation.

Human- Generation of clinically relevant pluripotent stem cells

 A major problem limiting the clinical use of ESCs is the potential for tissues derived from these cells to be rejected by receiving patients. The most attractive solution to this problem comprises transplanting tissues derived from ESCs genetically matched to each patient. Somatic cell nuclear transfer (SCNT), where an adult somatic cell is returned to a pluripotent state (a process called reprogramming) following transplantation to an enucleated oocyte, can be used to provide such cells, however, ethical and practical limitations associated with both oocyte donation and human SCNT raise serious concerns about the suitability of this method.

Alternative approaches to reprogramming cells include 1) fusion of somatic cells with ESCs and 2) introduction of a few key pluripotent genes into the somatic cells.

Our lab is undertaking research in all three methods of reprogramming to explore the potential to improve the following: reprogramming of somatic cells, generation of pluripotent stem cells in other species using iPS technology, and derivation of ESCs. The aim is to develop safe, clinically relevant pluripotent cells, which will circumvent the issues relating to immune rejection of therapeutic cells by the recipient patients.

Livestock- Generation and characterization of pluripotent stem cells from large animals

Generation of pluripotent stem cells from livestock species are of interest for a number of reasons; they provide a unique source of cells from large animals that allow specific traits to be engineered for agricultural or pharmaceutical purposes, and they provide large animal models for studying developmental biology and regenerative medicine. However stable ES cell lines have not been generated in any livestock species.

We have successfully generated induced pluripotent stem cells (iPSCs) in livestock. And our current research is aimed at in depth characterization of the putative iPSCs we have generated.

¹Tat PA, Sumer H, Jones K, Upton K. and Verma, PJ. (2010). The efficient generation of induced pluripotent stem (iPS) cells from adult mouse adipose tissue derived and neural stem cells. Cell Transplantation 19(5):525-36. Epub 2010 Feb 8.

²Liu J, Ashton MP, Sumer H, O’Bryan MK, Brodnicki TC, Verma PJ. (2011) Generation of Stable Pluripotent Stem Cells from Non-Obese Diabetic (NOD) Mouse Tail-Tip Fibroblasts. Diabetes; 60(5):1393-8. Epub 2011 Apr 4

³Liu J, Sumer H, Leung J, Upton K, Dottori M, Pébay A and Verma PJ. (2010) Late passage human fibroblasts induced to pluripotency are capable of directed neuronal differentiation. Cell Transplantation; 20(2):193-203. Epub 2010 Aug 17.

⁴Liu J*, Verma PJ*, Evans-Galea M, Delatycki M, Michalska A, Leung J, Crombie D, Joe Sarsero J, Williamson R, Dottori M, Pébay A. Generation and Function of Induced-Pluripotent Stem Cell Lines from Friedreich Ataxia Patients. Stem Cell Reviews and Reports; 7(3):703-13.

⁵Sumer H, Liu J, Malaver-Ortega LF, Lim ML, Khodadi K. and Verma PJ.  (2011) Nanog is a key factor for induction of pluripotency in bovine adult fibroblasts. Journal of Animal Science; 89(9):2708-16. Epub 2011 Apr 8.

⁶Liu J, Balehosur D, Murray B, Kelly JM, Sumer H and Verma PJ. (2011) Generation and characterization of reprogrammed sheep induced pluripotent stem cells. Theriogenology (Accepted July 7, 2011)