Therapeutic benefits in thalassemic mice transplanted with long-term-cultured bone marrow cells.

OBJECTIVE: Autologous bone marrow (BM) cells with a faulty gene corrected by gene targeting could provide a powerful therapeutic option for patients with genetic blood diseases. Achieving this goal is hindered by the low abundance of therapeutically useful BM cells and the difficulty maintaining them in tissue culture long enough to complete gene targeting without differentiating. Our objective was to devise a simple long-term culture system, using unfractioned BM cells, that maintains and expands therapeutically useful cells for ≥4 weeks. MATERIALS AND METHODS: From 2 to 60 million BM cells from wild-type (WT) mice or from mice carrying a truncated erythropoietin receptor transgene were plated with or without irradiated fetal-liver-derived AFT024 stromal cells in 25-cm(2) culture flasks. Four-week-cultured cells were analyzed and transplanted into sublethally irradiated thalassemic mice (1 million cells/mouse). RESULTS: After 4 weeks, cultures with AFT024 cells had extensive "cobblestone" areas. Optimum expansion of Sca-1-positive cells was 5.5-fold with 20 × 10(6) WT cells/flask and 27-fold with 2 × 10(6) truncated erythropoietin receptor transgene cells. More than 85% of thalassemic mice transplanted with either type of cells had almost complete reversal of their thalassemic phenotype for at least 6 months, including blood smear dysmorphology, reticulocytosis, high ferritin plasma levels, and hepatic/renal hemosiderosis. CONCLUSIONS: When plated at high cell densities on irradiated fetal-liver-derived stromal cells, BM cells from WT mice maintain their therapeutic potential for 4 weeks in culture, which is sufficient time for correction of a faulty gene by targeting.

Laparoscopic incisional hernia repair in liver transplant and other immunosuppressed patients.

We report the early results of laparoscopic incisional hernia repair in a small group of immunosuppressed patients and compare these results with a cohort of patients with open repair. We describe a modification used to secure the cephalad portion of the Gore-Tex mesh in high epigastric incisional hernias often encountered after liver transplantation. Data were gathered retrospectively for all incisional hernia repairs by our group from March 1996 to January 2001. Twelve of 13 attempted patients had successful completion of their laparoscopic hernia repairs with no reported recurrences to date. Two of these procedures were performed for recurrent hernias. We completed nine of nine attempted laparoscopic hernia repairs in liver transplant patients with epigastric incisional hernias. We repaired two of three attempted lower midline incisional hernias in renal disease patients. One of these patients was soon able to reuse his peritoneal dialysis catheter. A total of 15 patients, 12 with liver transplants, underwent open repair of their incisional hernias. These patients had seven recurrences and/or serious mesh infections with five patients electing repeated operations. In our initial series, laparoscopic mesh repair of incisional hernias is practical and safe in the abdominal organ transplant population with a low incidence of early recurrence and serious infections.

Incidence of donor renal fibromuscular dysplasia: does it justify routine angiography?

BACKGROUND: The use of digital subtraction angiography (DSA) versus helical CT angiography (CTA) or MR angiography (MRA) for live renal donor evaluation is still controversial. Although CTA and MRA can detect some proximal moderate to severe arterial changes caused by fibromuscular dysplasia (FMD), mild and distal moderate FMD are not detected well without angiography. METHODS: This is a retrospective chart review of all potential, normotensive live renal donors at our center from July 1995 to June 2001. One hundred fifty-nine patients completed the donor evaluation process and underwent DSA. RESULTS: Seven cases of FMD, an incidence of 4.4%, were discovered. These patients were eliminated from donation. The distribution of renal vessels for our 159 patients was single arteries bilaterally, 64.8%; single left with multiple right, 16.4%; double left with single right, 9.4%; and multiple bilateral arteries, 9.4%. Three of the seven FMD patients had bilateral disease. Two of the seven (28.6%) FMD patients have subsequently required antihypertensive medications, with one requiring angioplasty of a progressive FMD stenotic lesion. CONCLUSIONS: We are concerned that CTA or MRA may overlook mild cases of DSA-detectable FMD. All seven FMD patients had single left renal arteries and would have undergone left donor nephrectomy. This would have resulted in their remaining right native kidneys having mild to moderate FMD in six of seven patients and in four donor kidneys having mild to moderate FMD. The need for antihypertensive medications in two of these seven potential donors within 4 years of their evaluation supports previous literature reports.