Wednesday, May 7, 2008

[StemCells] Corneal surface reconstruction from SC allografts

OCULAR SURGERY NEWS EUROPE/ASIA-PACIFIC EDITION May 2008

Ex vivo stem cell allograft aids in corneal surface reconstruction

Allogeneic stem cells reduced inflammation, epithelial defects,
photophobia and pain, and restored corneal phenotype.

By Matt Hasson
NEW ORLEANS — Ex vivo expanded stem cell allografts enhanced corneal
stability with a low rejection rate in treating acute limbal stem
cell deficiency, according to a surgeon speaking here.

Sheraz M. Daya, MD, speaking on behalf of colleague Omar J. Hakim,
MD, presented the results of a study at the American Academy of
Ophthalmology annual meeting.

Dr. Daya focused on early results of 10 procedures that he and
colleagues published in Ophthalmology in 2005 and later findings on
the same cases and a further 28 procedures.

He also cited a study published in Lancet in which Graziella
Pellegrini, PhD, and colleagues reported on autologous stem cell
transplantation.

For their study, Dr. Daya and colleagues grew grafts on plastic using
Pellegrini's method.

Allogeneic corneal limbal stem cells were transplanted to the
recipient eye after the conjunctival pannus was removed. The postop
treatment regimen included the immune-suppressive agent cyclosporine
(2 mg/kg to 3 mg/kg daily for 9 months) and topical steroids, Dr.
Daya said.

"We also demonstrated that there was no donor DNA 9 months after
allograft transplantation," he said, suggesting the host restored its
own stem cells.

The procedure
The researchers took limbal tissue cells from corneal transplant
tissue and cultured about three or four sheets at a time. These
sheets took 2 to 3 weeks to form and were transferred to the
operating theater for grafting.

Cells cultured on plastic showed more normal characteristics than
cells cultured on amniotic membrane, Dr. Daya said.

"This is our choice based on preliminary basic science we did looking
at histology of this type of culture vs. growing cells on amnion," he
said. "Cells grown on amnion did not look normal in terms of polarity
and morphology."

Ex vivo allograft is feasible for treating bilateral limbal stem cell
deficiency, Dr. Daya said.

"We learned that allograft culture can be used in bilateral disease,"
he said. "There's no harm to any fellow eye or any donating eye from
which we grafted."

In the Pellegrini study, the researchers noted that unilateral limbal
stem cell deficiency can be treated with limbal grafts taken from the
unaffected eye, but a limbal graft must be taken from the fellow eye,
a potential risk. Autologous grafting is not feasible for bilateral
limbal stem cell deficiency, as there is no donor limbus available,
they said.

The ex vivo allograft may involve a lower risk of rejection than
other methods, Dr. Daya said.

"There's theoretically less chance of rejection because there are no
antigen-presenting Langerhans cells and only a large volume of what
we presume are stem cells," he said. "DNA evidence showed a reduced
or no need for immune suppression for more than 9 months following
the procedure, as donor stem cells appeared to be replaced by host
cells."

Study results for the first 10 eyes treated for limbal stem cell
deficiency showed no presence of donor cell DNA after 1 year, Dr.
Daya said.

Ocular surface stability
The current study focused on 38 allografts performed on 35 eyes of 34
patients. All procedures involved allografts, and some eyes later
underwent penetrating or deep anterior lamellar keratoplasty.

Study results showed 11 procedures failed in nine eyes; six failures
were primary and five were secondary after initial success, Dr. Daya
said.

Surface stability was maintained in 26 eyes (74%), Dr. Daya said. The
researchers focused on six outcome measures: inflammation,
conjunctivalization, persistent epithelial defect, photophobia, pain
before surgery and pain at final follow-up.

"You can see a definite decrease in these parameters," Dr. Daya said.
Corneal opacification was also reduced.

Inflammation and the presence of lid disease were other key variables
that affected long-term outcome.

"We took a look at a patient's conjunctival involvement, and you can
see here that the ones that did not have continued inflammation did
better than those that had persistent inflammation," Dr. Daya
said. "We also found that good lid apposition is very important, as
it ensures a watertight closure, ensuring the eyes remain moist."

For more information:
Sheraz M. Daya, MD, can be reached at Centre for Sight Corneoplastic
Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, W. Sussex
RH19 3DZ, United Kingdom; +44-1342-321-201; fax: +44-1342-325-873; e-
mail: sdaya@centreforsight.com.
References:
Daya SM, Watson A, et al. Outcomes and DNA analysis of ex vivo
expanded stem cell allograft for ocular surface reconstruction.
Ophthalmology. 2005;112:470-477.
Pellegrini G, Traverso CE, et al. Long-term restoration of damaged
corneal surfaces with autologous cultivated corneal epithelium.
Lancet. 1997;349:900-993.
Matt Hasson is an OSN Staff Writer who covers all aspects of
ophthalmology. He focuses on regulatory, legislative and practice
management topics.

http://www.osnsupersite.com/view.asp?rID=28077

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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