Alpha-fetoprotein-a potential biomarker of intestinal regeneration in the infant.

ABSTRACT

We hypothesise that the human infant, whether born prematurely or at term, may have special capacities when mounting a healing response to severe post-natal gastrointestinal injury consequent upon stem cells of endodermal origin, located in the infant gut, persisting beyond the intrauterine period. Should such endodermal stem cells persist beyond birth, and should they survive any gastro-intestinal injury, there would be a possibility for them to be re-activated, and then to differentiate into progeny cells appropriate to replacement of the destroyed intestinal cell type(s). We therefore postulate that in infants who survive significant intestinal necrosis requiring surgical excision in the perinatal period, a component of the recovery process may include some degree of intestinal regeneration. Evidence for the regeneration of intestine would be evinced by measurement of a biomarker in the plasma of recovering infants--alpha-fetoprotein (AFP)--as this protein would be produced by early generations of these putative replacement progeny intestinal cells. We would anticipate an initial significant rise in the plasma AFP, prior to a plateau in levels, and then a subsequent fall in plasma AFP values. This would indicate the activity, then subsequent cessation, of any intestinal cell regenerative process. We have recently published a previously undescribed pattern of anomalous serial plasma concentrations of AFP in several infants who survived following significant intestinal necrosis and subsequent surgical resection. We consider this novel hypothesis, and our associated observation of another cause of rising AFP in the post-natal period, to support our contention regarding the presence and potential of intestinal stem cells, and a regenerative process within the infant gastro-intestinal system. This hypothesis has important implications for the understanding of the physiologic responses following gut cell necrosis in the human newborn as well as future approaches to research directions, clinical support and potential treatment modalities, during their recovery phase. Further studies are needed to confirm our hypothesis.