ISLET TRANSPLANTS ALLOW MORE INSULIN-INDEPENDENCE IN DIABETICS

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ISLET TRANSPLANTS ALLOW MORE INSULIN-INDEPENDENCE IN DIABETICS

Laurie Barclay, MD

SOURCE: Medscape Medical News

Aug. 28, 2002 — Success rates of islet transplantation in diabetes mellitus are

now approaching 80%, according to presentations from Aug. 27-30 at the

International Congress of the Transplantation Society in Hollywood, Florida. In

one trial of porcine islets mixed with sertoli cells on a subdermal stainless

steel mesh, six of 12 children had functioning grafts at 20 weeks without the

use of immunosuppressive drugs. Another group presented a case report of a

patient successfully transplanted with islets derived from a non-heart-beating

donor. In a separate study, adding perfluorocarbon to the standard solution for

cold preservation allowed successful transplantation from donors whose prolonged

ischemia times would have otherwise rendered them unacceptable.

New data from the International Islet Transplant Registry indicate that 28 (80%)

of 35 patients remain insulin-free one year after receiving islet cell

transplants alone, a marked improvement over the 14% success rate reported for

1998-2000, and a success rate comparable to that seen with whole pancreas

transplantation. Mathias D. Brendel and colleagues from Giessen, Germany,

analyzed 388 adult islet allograft transplantations in patients with type-1

diabetes mellitus treated at 39 institutions worldwide from 1990 through

December 2001. Through December 2000, 139 simultaneous islet-kidney transplants

showed persistent islet graft function in 79% at one month and in 47% at one

year.

According to a separate presentation by A. Valdes- Gomzalaez from the

Children's Hospital of Mexico in Mexico City, transplantation of testicular

sertoli cells along with islet cells from neonatal pigs may subdue T cells

responsible for rejection without the use of immunosuppressive drugs. The cells

were delivered into a stainless-steel mesh tube that had been implanted under

the skin eight weeks before the cell transplants.

" These observations suggest that transplantation of a mixture of porcine islets

and sertoli cells into an appropriate environment might provide a safe therapy

for type 1 diabetes with minimal disruption of the immune system, " the authors

write.

This technique reduced insulin-dependence in six of 12 children with type 1

diabetes, ranging in age from 11 to 17 years, none of whom received

immunosuppressive drugs. These six patients have functioning grafts, no evidence

of rejection, and improved islet function after receiving additional

transplanted islets at 20 weeks. One child remains insulin-free at one year, and

a second child was insulin-free for six months and currently requires 75% less

insulin than before the transplant. The porcine islets survived and functioned

even in the presence of high quantities of natural, preformed antiporcine

antibodies, thanks to the sertoli cells, which appeared to reduce levels of the

key antibody anti GAL IgG between week four and 12, when grafts were functioning

well. Retransplantation of islets did not stimulate a secondary GAL antibody

response.

" Whether these results can be duplicated by another center remains to be seen, "

said Congress co-chair Camillo Ricordi from the Diabetes Research Institute at

the University of Miami in Florida. " The scientific community at large may be

skeptical until more data is available and more patients are studied. "

In a separate study, Ricordi's group added perfluorocarbon to the standard

University of Wisconsin (UW) organ preservation solution, allowing them to use

islet cells from marginal organs that would have typically been discarded under

current organ donor criteria. Of nine patients receiving perfluorocarbon

(PFC)-preserved islet cells, all were initially able to discontinue insulin. One

patient had to resume insulin injections at one year and another at six months

after transplantation, but at 19% of their pretransplant dose. The remaining

seven patients continue to be insulin-free, three for nearly one year.

" These excellent preliminary results are very encouraging and may allow for

improved clinical utilization not only of older donors, but also of pancreata

with more prolonged cold ischemia times, " the authors write. " The PFC/UW method

is now routinely used at our institution for incubation of human pancreata of

all ages, for a period of 2-8 hours before islet processing. "

Still another approach to increase the available supply of donor islet cells is

human islet transplantation from a non-heart beating donor (NHBD), as reported

by J. F. Markmann from the Hospital of the University of Pennsylvania in

Philadelphia. The first recipient of NHBD islets remained insulin-independent

four months after transplant.

" In view of the donor shortage, isolated islet transplantation is unlikely to

become the treatment of choice for diabetes if each recipient requires islets

from several donors, since whole pancreas transplantation requires only one

donor, " he writes. " We determined in experimental assays that NHBDs provide an

excellent source of large numbers of normally functioning islets and report the

first successful human islet transplant using a NHBD. "

Mark E. Armstrong

NW Rep, PAI

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