Cell encapsulation as a potential nondietary therapy for maternal phenylketonuria.
OBJECTIVE
The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria.


METHODS
Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry.


RESULTS
Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly decreased the Phe concentration in the media by up to 85% compared with media alone.


CONCLUSIONS
Both unencapsulated and encapsulated cells overexpressing PAH significantly reduce Phe in vitro. Studies using phenylketonuria model mice will be important in determining the ability of our therapy to prevent the teratogenic effects of elevated maternal Phe in maternal phenylketonuria.
Santillan
Donna A
DA
Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Santillan
Mark K
MK
Hunter
Stephen K
SK
D000464:Alginates; D000818:Animals; D002460:Cell Line; D004337:Drug Carriers; D005260:Female; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D051379:Mice; D008863:Microspheres; D010651:Phenylalanine Hydroxylase / Q000378:metabolism*; D010661:Phenylketonurias / Q000628:therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000628:therapy*
D000464:Alginates; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D010651:Phenylalanine Hydroxylase