Coimplantation of small fragments of human fetal thymus and fetal liver into immunodeficient SCID mice resulted in the formation of a unique structure (Thy/Liv). Thereafter, the SCID-hu mice showed reproducible and long-term reconstitution of human hematopoietic activity. For periods lasting 5-11 mo after transplantation, active T lymphopoiesis was observed inside the grafts and cells that were negative for T cell markers were found to have colony-forming units for granulocyte/macrophage (CFU-GM) and erythroid burst-forming unit (BFU-E) activity in the methylcellulose colony assay. In addition, structures similar to normal human bone marrow were observed inside the Thy/Liv grafts, consisting of blast cells, mature and immature forms of myelomonocytic cells, and megakaryocytes. These data indicate long-term maintenance, in vivo, of human progenitor cells for the T lymphoid, myelomonocytic, erythroid, and megakaryocytic lineages. The role of the implanted fetal liver fragments was analyzed using HLA-mismatched Thy/Liv implants. The HLA type of the liver donor was found on T cells and macrophages in the graft. In addition, cells grown in the methylcellulose colony assay and cells in a bone marrow-like structure, the "thymic isle," expressed the HLA type of the liver donor. Thus, the Thy/Liv implants provided a microenvironment in which to follow human hematopoietic progenitor cells for multiple lineages. The formation of the Thy/Liv structures also results in a continuous source of human T cells in the peripheral circulation of the SCID-hu mouse. Though present for 5-11 mo, these cells did not engage in a xenograft (graft-versus-host) reaction. This animal model, the first in which multilineage human hematopoietic activity is maintained for long periods of time, should be useful for the analysis of human hematopoiesis in vivo.

Background and purpose

Endovascular navigation under MR imaging guidance can be facilitated by a catheter with steerable microcoils on the tip. Not only do microcoils create visible artifacts allowing catheter tracking, but also they create a small magnetic moment permitting remote-controlled catheter tip deflection. A side product of catheter tip electrical currents, however, is the heat that might damage blood vessels. We sought to determine the upper boundary of electrical currents safely usable at 1.5T in a coil-tipped microcatheter system.

Materials and methods

Alumina tubes with solenoid copper coils were attached to neurovascular microcatheters with heat shrink-wrap. Catheters were tested in carotid arteries of 8 pigs. The catheters were advanced under x-ray fluoroscopy and MR imaging. Currents from 0 mA to 700 mA were applied to test heating and potential vascular damage. Postmortem histologic analysis was the primary endpoint.

Results

Several heat-mitigation strategies demonstrated negligible vascular damage compared with control arteries. Coil currents ≤300 mA resulted in no damage (0/58 samples) compared with 9 (25%) of 36 samples for > 300-mA activations (P = .0001). Tip coil activation ≤1 minute and a proximal carotid guide catheter saline drip > 2 mL/minute also had a nonsignificantly lower likelihood of vascular damage. For catheter tip coil activations ≤300 mA for ≤1 minute in normal carotid flow, 0 of 43 samples had tissue damage.

Conclusions

Activations of copper coils at the tip of microcatheters at low currents in 1.5T MR scanners can be achieved without significant damage to blood vessel walls in a controlled experimental setting. Further optimization of catheter design and procedure protocols is necessary for safe remote control magnetic catheter guidance.