Viable monkey clone achieved with chimeric placenta

Chinese scientists are reporting the successful cloning of a rhesus monkey, thanks to a new adaptation of the technique originally used to clone Dolly the Sheep.

The rhesus monkey (Macaca mulatta) has survived for 2 years, in part due to the research team’s use of a new technique to develop a healthy placenta.

To achieve this, the group from the Chinese Academy of Sciences used somatic cell nuclear transfer (SCNT) – a form of cloning where the nucleus of a body cell (such as skin, blood or muscle cell) is implanted into and replaces the nucleus of an unfertilised egg cell.

Once inserted, the egg might reprogram the implanted nucleus to begin dividing and form an embryo.

These embryos can be inserted into the uterus of the same or similar species to produce a near-identical genetic copy. SCNT is the pioneering method used to clone Dolly the Sheep in 1996 and has been used as a method to obtain embryonic stem cells.

But creating viable offspring is not guaranteed. Most attempts to clone mammals result in death – often a 1-3% live birth rate – and rhesus monkey cloning has previously resulted in just one live newborn that died shortly after.

One reason for such low success in SCNT mammal cloning appears because of abnormalities in the placenta’s development.

The researchers found higher levels of calcification, where placental tissue develops small calcium deposits that can impede nutrient and oxygen flow to the foetus, in SCNT placentas compared to those developed from directly injecting sperm into egg cells using an IVF technique called Intracytoplasmic Sperm Injection (ICSI).

To reduce the risk of these issues, they developed a SCNT variation where trophoblasts – specialised cells that provide nutrition to early-stage embryos – are replaced with those from ICSI embryos.

Through this method, they were able to improve normal placental development.

In their report, published today in the journal Nature Communications, they confirm having transferred 11 of these reconstructed embryos to 7 surrogate mothers. One of the mothersproduced twins, which were spontaneously aborted. Another produced a single male foetus which has now lived for two years.

They also verified that no ‘chimerism’ – where genetic material is obtained from more than one embryo – occurred in the male rhesus baby, although some material from the ICSI embryos was detected in the healthy placenta.

The researchers hope the development of their trophoblastic replacement technique will help improve the viability of SCNT clones, writing the strategy “has great promise for improving the success rates of [SCNT] by addressing issues specifically related to the trophectoderm, which plays a crucial role in early embryonic development and implantation”.

Among other possible applications, SCNT has been proposed as a pathway to rescuing critically endangered species, whether by creating embryos for implantation in suitable females or through interspecies surrogacy.

Some members of the research team were also involved in recent experimentation with monkeys, achieving a live birth of a cynomolgus monkey with genetic information from two distinct embryos.

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