Therapeutic Cloning and Parthenogenetic Stem Cells

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Therapeutic cloning offers a strategy for generating autologous (genetically identical to graft recipient) cells for transplantation therapy. We have previously shown that such embryonic stem cells can be generated in mice via nuclear transfer (ntES stem cells).

Donor nuclei can be obtained from an adult animal (e.g., after a tail biopsy of the mouse). ntES stem cells appear to have the same stem cell properties as regular ES cells but are genetically matched to the adult donor animal. These cells can be subsequently coaxed into specialized cell types, such as midbrain dopamine neurons (cells lost in Parkinson's Disease). We currently attempt a proof-of-princple application of therapeutic cloning by curing Parkinsonian mice with stem cells derived via nuclear transfer from the mouse's own tail.

	[Enlarge Image] Monkey parthenogenetic stem cells were differentiated into dividing neural precursor cells (A, B). Such precursors could be subsequently coaxed into astrocytes (C) or into neurons (D), including midbrain dopaminergic neuron (E) releasing the neurotransmitter dopamine measured by HPLC analysis.

Parthenogenesis allows the generation of pluripotent ES-like stem cells via activation of an unfertilized egg cell. This is a process that does not require fertilization or any contribution of sperm. The genomic DNA of the resulting cells is completely maternally derived. Our lab has demonstrated the neural differention potential of such cells. Parthenogenetic stem cells could serve as an alternative source for autologous cell therapy.

Parthenogenetic stem cells are also an interesting tool to elucidate the role of imprinting during development, as these cells lack paternal imprinting. Current studies address the in vivo function of parthenogenetic stem cells after transplantation in animal models of neurodegenerative disease.