Autologous limbal stem cell transplantation successful in patients with chemical burn
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Cultivated autologous limbal stem cell transplantation was successfully performed at Massachusetts Eye and Ear in four patients with chemical burns.
First of its kind in the U.S., this procedure is “a big step for regenerative medicine,” and “may pave the way for better care for patients with corneal blindness, who have long needed better solutions for their condition,” Ula V. Jurkunas, MD, said in a press release.
Jurkunas was not only the surgeon who performed the procedures, but also at the heart of the research project that led to the development of cultivated autologous limbal epithelial cell transplantation (CALEC) at Massachusetts Eye and Ear.
In 2006, as a junior clinical scientist, she received from the National Institutes of Health (NIH) a grant to investigate ways of healing injured corneas by regeneration techniques and became leader of a team that joined the competencies of researchers from her institution, Boston Children’s Hospital and Dana-Farber Cancer Institute.
The procedure
Small stem cell biopsy samples, 2 mm2 or 1 clock hour, harvested from the patients’ own healthy eye under topical anesthesia were expanded and grown on a membrane substrate at Dana-Farber Cancer Institute, under the direction of Jerome Ritz, MD. After about 3 weeks, when the limbal stem cell graft was ready, Jurkunas performed the transplantation procedure.
“Limbal epithelial sheets are isolated from the biopsy by enzymatic digestion and then dissociated into a single cell suspension,” Jurkunas told Healio/OSN. “Cells are then plated into a six-well culture plate, in serum-free complete corneal epithelial cell media. At the end of the primary culture, cells are detached, harvested, washed and resuspended in complete corneal epithelial cell media and seeded on a de-epithelialized AmnioGraft (Bio-Tissue) to generate CALEC.”
Cell growth, she explained, is monitored under the microscope until culture reaches confluence. When confluent, the CALEC graft is transferred to a hypothermic biopreservation solution and maintained at 2°C to 8°C in a validated container for transport and storage until transplantation. Final culture supernatant is retained for quality control testing.
Transplantation in the recipient eye is performed under peribulbar anesthesia in the operating room.
“A 360-degree conjunctival peritomy is performed and fibrovascular tissue is dissected from the limbus and the cornea. Then, the trephined CALEC graft is transferred onto the ocular surface with the epithelium side up and secured with interrupted 10-0 Vicryl sutures and/or fibrin glue. At the end of the procedure, fluorescein is used to assess epithelial integrity. Lack of fluorescein uptake in the central cornea will indicate that epithelium of the CALEC graft is intact,” Jurkunas said.
Advantages
CALEC is designed to help patients with chemical injuries and other traumatic or infectious causes of limbal stem cell deficiency (LSCD) in one eye.
“As compared to other techniques currently used, it has the advantage of providing an autologous source of cells, which does not carry the risk of immunologic rejection. It also creates a stable bed for future allogeneic corneal transplantation if necessary,” Jurkunas said.
Compared with conjunctival limbal autograft (CLAU), another and already well-established technique of autologous tissue grafting, CALEC requires a smaller biopsy from the donor eye, significantly lowering the risk of inducing LSCD in the healthy eye.
The four patients treated with CALEC so far are “doing great,” Jurkunas said. They no longer experience pain from their chemical injury and will be followed over the long term to monitor their progress. Now that feasibility of the technique has been established with no immediate safety concerns, more patients with corneal damage will be included in a second phase of the trial, in which CALEC will be evaluated as a method for potentially restoring vision, by itself or by re-creating the conditions for corneal transplantation.
“We are proud to have developed this novel treatment from the lab bench to the bedside in an academic medical setting, without industry support,” Jurkunas said.
The clinical trial represents the first human study of a stem cell therapy to be funded by the National Eye Institute, a part of the NIH.
For more information:
- Ula V. Jurkunas, MD, can be reached at Ula_Jurkunas@meei.harvard.edu.
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