Transplantation of fetal porcine pancreas to diabetic or normoglycemic nude mice. Evidence of a rapid engraftment process demonstrated by blood flow and heat shock protein 70 measurements.
The aims of the present investigation were to study the blood flow rate in transplanted fetal porcine islet-like cell clusters (ICC) with laser-Doppler flowmetry and to evaluate the influence of hyperglycemia on this process. In order to investigate the degree of stress in transplanted beta cells during engraftment, the amount of heat shock proteins (HSP) or stress proteins was measured. ICC were prepared from the fetal porcine pancreas by employing a tissue culture technique. A total volume of 6 microliters (approximately 750) ICC was transplanted under the left kidney capsule of either normo- or hyperglycemic C57BL/6J nude mice. The blood flow to the xenogeneic islet graft and the adjacent kidney parenchyma were measured with laser Doppler flowmetry (LDF). Within 2 hr after transplantation (day 0) or 3, 6, 9, 12 (both normo- and hyperglycemic recipients), 15, 40, or 85 (only normoglycemic recipients) days after implantation of ICC into the nude mice, the hsp70 contents of the grafts were analyzed by means of an immunoassay. Revascularization of the subcapsular ICC graft was initiated rapidly, and 3 days posttransplantation the nutritional blood supply constituted 70% of the adjacent kidney blood flow. This figure increased with time after implantation until the ICC graft had equal or even higher blood perfusion than the adjacent kidney parenchyma. Hyperglycemia in recipients did not affect the revascularization process. Hsp analysis from ICC in culture demonstrated a surprisingly high content of hsp70. However, 3-9 days after transplantation the hsp70 content was markedly reduced in both the normo- and hyperglycemic group and then remained low in both groups. Thus, the present study showed that ICC transplanted into normo- or hyperglycemic nude mice were rapidly revascularized, and that the production of hsp70 was lowered already 3 days after transplantation when compared with cultured ICCs.
Sandberg
J O
JO
Department of Medical Cell Biology, Uppsala University, Sweden.
Margulis
B
B
Jansson
L
L
Karlsten
R
R
Korsgren
O
O
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017690:Cell Transplantation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000601:surgery*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D016332:Fetal Tissue Transplantation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply* / Q000196:embryology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011247:Pregnancy; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous
D001786:Blood Glucose; D018840:HSP70 Heat-Shock Proteins; D000241:Adenosine; D004837:Epinephrine