A Technological Alternative to Therapeutic Cloning for the
Production of Blood

By Richard Mollard, MBA, PhD*

Summary
Articles in the scientific journals Science¹ and Genes & Development² together describe technology permitting the production of immuno-compatible blood suitable for stable and functional transplantation into mice without the need for immunosuppressive drug regimes. Although this technology remains in early stages, these articles are significant because if the technology can be translated in an acceptable fashion to humans, society will be offered an alternative to therapeutic cloning for generating at least some types of immuno-matched tissue for treating injury and disease. Importantly and distinct from therapeutic cloning, the tissue described in these studies can be derived from activated eggs that lack the innate potential to develop into a human being if transferred to a mother in an attempt at pregnancy. That is to say that no fertilisation step either natural or artificial is necessary to achieve this process.

Background
”Higher vertebrates” such as people reproduce sexually, deriving one set of chromosomes from the egg of the mother and one from the sperm of the father. Some reptiles, birds, fish and insects, however, can reproduce either sexually or asexually. Asexual reproduction in this context occurs through a process known as parthenogenesis whereby the mother produces offspring by activating her eggs to develop in the absence of fertilisation by a male. Instead of possessing one set of chromosomes from the mother’s egg and one set of chromosomes from the father’s sperm, the resulting embryo possesses chromosomes that come only from the mother’s egg. Having this choice allows these animals flexibility in respect to responding to specific environmental conditions.

Human development has an obligate requirement for one set of chromosomes each from the mother and father and hence humans currently lack an ability to choose between sexual or asexual reproduction. Yet human eggs can still undergo spontaneous parthenogenetic activation to commence division in the absence of fertilisation. Activated human eggs fail to develop into viable human fetuses due to strong restrictions placed upon their chromosomes. A similar property holds true for mouse eggs. They can spontaneously activate, yet these eggs do not possess an innate capacity to develop into viable mouse fetuses or new-borns.

Past Technology
In the laboratory researchers study parthenogenetic mouse eggs to understand mechanisms of inheritance from the mother or father’s chromosomes. There are, however, several ways of studying these mechanisms. So researchers also transplant either maternal or paternal chromosomes into enucleated unfertilised or activated eggs. These eggs also do not develop into viable fetuses. Of interest for therapeutic purposes, each of these configurations develop into blastocyst-like structures (known as uni-parental blastocysts) from which embryonic-like stem cells have been derived. These embryonic-like stem cells could, in theory, be useful for treating a wide range of diseases.

State-of-the-Art and Significance
Researchers have in the past described transplantation of neural-like tissue derived from the embryonic-like stem cells of parthenogenetic eggs.³ The articles in Science and Genes & Development, however, take this technology one step further. The article in Science demonstrates that tissue can match the immune type of the donor and the article in Genes & Development describes the ability to form a tissue (blood) that can be transplanted and engraft in a functionally relevant context without immune-rejection.

The researchers acknowledge that the capacity of these uni-parental embryonic-like stem cells to produce all functional cell types of the body may be limited. Furthermore, they point out that although no sign of cancer or other defects following transplantation were observed in these shorter-term mouse studies, longer-term studies are required to demonstrate safety before this type of technology may be confidently transferred to humans for treatments. However, this type of technology is potentially very powerful as it may provide women the choice of deriving matched tissue from their own eggs. This choice, therefore, may be free of the moral and ethical caveats linked to the sourcing of surrogate eggs and the production of therapeutic clones.

Notes
1. Kim et al., Science, 2007, 315: p482-6.
2. Eckardt et al., Genes Dev., 2007, 21: p409-19.
3. Sanchez-Pernaute, Stem Cells, 2005 23: p914–922.

*Author affiliation
Richard Mollard, MBA, PhD
Head: Stem Cells, Respiratory Development and Tissue Engineering
The Department of Biochemistry and Molecular Biology
Monash University
Clayton 3800
Australia

Posted March 18, 2008