ANALYSIS OF HEPATOCYTE DISTRIBUTION AND SURVIVAL IN VASCULAR BEDS WITH CELLS MARKED BY TC-99M OR ENDOGENOUS DIPEPTIDYL PEPTIDASE-IV ACTIVITY

Knowledge of the kinetics of cell distribution in vascular beds will h elp optimize engraftment of transplanted hepatocytes, To noninvasively localize transplanted cells in vivo, we developed conditions for labe ling rat hepatocytes with Tc-99m-pertechnetate. The incorporated Tc-99 m was bound to intracellular proteins and did not impair cell viabilit y. When Tc-99m hepatocytes were intrasplenically injected into normal rats, cells entered liver sinusoids with time-activity curves demonstr ating instantaneous cell translocations. Tc-99m activity in removed or gans was in liver or spleen, and lungs showed little activity, However , when cells were intrasplenically transplanted into rats,vith portasy stemic collaterals, Tc-99m appeared in both liver sinusoids and pulmon ary alveolar capillaries, To further localize cells, we transplanted D PPIV+ F344 rat hepatocytes into syngeneic DPPIV- recipients, Histochem ical staining for DPPIV activity demonstrated engraftment of intrasple nically transplanted cells in liver parenchyma, In contrast, when Tc-9 9m hepatocytes were injected into a peripheral vein, cells were entrap ped in pulmonary capillaries but were subsequently broken down with re distribution of Tc-99m activity elsewhere, Intact DPPIV+ hepatocytes w ere identified in lungs, whereas only cell fragments were present in l iver, spleen, or kidneys, These findings indicate that although the pu lmonary vascular bed offers advantages of easy accessibility and a rel atively large capacity, significant early cell destruction is an impor tant limitation. (C) 1997 Elsevier Science Inc.