Bangalore: An international team of ophthalmologists has expressed grave concern over stem cell transplant procedures used by doctors in India and some other countries for preventing blindness.

In the last four years, surgeons at the L.V. Prasad Eye Institute (LVPEI) in Hyderabad have carried out this transplant on over 350 patients to repair their damaged cornea for restoring vision.
 

The feat was lauded by India's President A.P.J. Abdul Kalam and earned LVPEI surgeon Virender Sangwan the coveted Bhatnagar prize for 2005.

Now a team of American and Australian ophthalmologists has thrown a bombshell.
 

In a report in the December issue of Archives of Ophthalmology published by the American Medical Association they warn that the currently used transplant procedures carry potential health risks not only to individuals but also to the wider community" because they "ely on the use of materials from animal and human donors.

The use of such material can potentially induce "disease transmission through contamination with bacteria, viruses, or other infectious agents", such as those responsible for what is commonly known as "mad-cow disease", the report said.

"It is a slowly ticking time bomb," Ivan Schwab, professor of ophthalmology at the University of California at Davis and lead author of the report told this reporter in an email interview.

 "I am not saying that this work should not be done, on the contrary - but society must be careful with this technology," he said.

Nigel Johnson and Damien Harkin of Australia's Queensland University of Technology and Queensland Eye Institute respectively are co-authors of the disquieting report.

Sangwan of LVPEI said that the report does "raise some important potential risk" but felt the risks have been hyped.

"All our patients are on regular follow up and we monitor carefully their progress," he said.

 He admitted that 30-35 percent of transplants failed but said that no patient had lost eyesight due to transplantation per se.

Ironically, Schwab and Harkin had themselves used this procedure on their patients before they realised two years ago that the nascent technology needed refinement in order to be used routinely for repairing damaged cornea.

Cornea is the clear, dome-shaped surface that covers the front of the eye. In case of damage due to burns or injury, stem cells residing in its rim called 'limbus' rally to support growth of new cornea.

 But if the limbus also gets damaged, the ready source of stem cells is gone and natural repair is not possible. Stem cell transplant helps such persons to grow new cornea.

To reconstruct corneas in such cases, doctors at LVPEI take out the limbal cells from the eye of a donor (or the healthy eye of the patient), grow them on a 'carrier'material (usually human amniotic membrane) and surgically transfer the construct on to the patient's damaged cornea.

Schwab and coworkers set out to carefully examine the protocols used in the manufacture of the bio-engineered construct to assess the risks. They reviewed 20 published reports of human trials conducted between 1996 and 2005 - two from LVPEI and the rest from six other countries.

They are not happy about what they found.
 

Their review revealed that 95 percent of protocols used one or more animal-derived products including fetal calf serum (FCS) and an overlapping 95 percent used one or more donor human tissues including amniotic membrane.
 

Bovine products represents the potential for transmissible spongiform encephalopathy (TSE) infection (of the brain) or fatal allergic reactions, the authors said adding that the use of commercially available fibrin tissue adds to the risk of microbial or prion contamination.

Notable prion afflictions (of the brain) include Creutzfeldt-Jacob disease, and mad cow disease.

They said that some of the protocols reviewed involved growing patient cells along with 3T3 cells (that come from mice) raising the spectre of 'xenozoonosis', or animal-to-human disease transmission.
 

"There have been a number of historical precedents for this," their report warned, adding that mice cells may contain unrecognized and unknown viral agents.
 

"Any xenozoonosis is potentially lethal to the recipient and a greater unknown risk to human community if the agent adapts to the human genome," they warned.

"Such transmission could present devastating consequences to the individual recipient as well as the wider community," they said.
 

Sangwan of LVPEI says has stopped using FCS.
 

 "The only donor tissue in our cultures is human amniotic membrane (HAM)," he said. But he could not comment on complications in his patients as "all the cases have not been analysed," they said.

Graziella Pellegrini, chief of stem cell laboratory at Giovanni Paolo Hospital in Venice, Italy, who was the first to demonstrate the limbal stem cell transplant in 1997, says no therapy is 'completely devoid' of risks.

"Cataract surgery has high incidence of complications but nobody thinks of stopping it," she said in an email interview.

"The key point is not to stop everything but to press those countries, where laws in the field were not written, to do something in the directions of rules and good manufacturing practices," she said.

Indian ophthalmologists who do not want to be named say that in the case of LVPEI this would mean quality control of HAM and sourcing the bovine serum only from herds certified to be free of prion disease as is done in the US and Australia. Right now the amniotic membranes are made in-house at LVPEI using placenta discarded by maternity clinics. Sangwan cannot say where FCS comes from but believes it is 'a standard source' 
Aware of the drawbacks of the current transplant procedures, some eye institutes in India are taking precautionary action.

Instead of using HAM, doctors at Shankar Nethralaya in Chennai have successfully cultivated limbal stem cells in 'Mebiol Gel', a biopolymer commercialized by a Japanese company. The transplantation is done as drops on the surface of damaged cornea avoiding any sutures.

"We have successfully used the technique on rabbits," H.N. Madhavan, who heads the team, told sources.

 "We have applied for government permission to start human trials," he said.